280. Liu, N. J.; Bao, H.; Li, N.; Yu, Y. X.; Han, J. S. Cholecystokinin

octapeptide reverses the inhibitory effect induced by

electroacupuncture on C-fiber evoked discharges. Int-J-

Neurosci. 1996 Sep; 86(3-4): 241-7; ISSN: 0020-7454.

ENGLAND. Extracellular single unit recordings were made from

spinal dorsal horn wide dynamic range neurons in spinal

transected, urethane-anesthetized rats. The unit discharges

elicited by noxious electrical stimulation of the hind paw

were suppressed by electroacupuncture (15 Hz, 0.3 ms, 3 mA,

30 min) placed at the hind leg points (S-36 and SP-6). Local

spinal superfusion with naloxone (20 micrograms/15

microliters) or CCK-8 (10 ng/15 microliters) attenuated,

whereas CCK-B receptor antagonist L365,260 (2.5

micrograms/15 microliters) enhanced the electroacupuncture

effect. These findings provide further evidence for the notion

that CCK-8, in the spinal cord, functions as an antiopioid

substrate that antagonizes opioid- or electroacupuncture-

induced analgesia.. 25126-32-3.

281. Liu, R. H.; Bertolotto, C.; Engelhardt, J. K.; Chase, M. H. Age-related

changes in soma size of neurons in the spinal cord motor

column of the cat. Neurosci-Lett. 1996 Jun 28; 211(3): 163-6;

ISSN: 0304-3940.

IRELAND. The present study was undertaken to examine the

effect of the aging process on the soma size and number of

motoneurons and interneurons in the motor column of the

spinal cord of old cats. Neurons in the motor column were

divided into small and large populations based on a bimodal

distribution of their soma cross-sectional areas. A 17%

decrease in the cross-sectional area of small neurons was

observed, this decrease was statistically significant (P <

0.0001). The cross-sectional area of large neurons decreased

by only 6%, which was statistically significant (P < 0.05). On

the other hand, there was no significant difference in the

number of large, small or of these combined population of

ventral horn neurons in the aged cats compared with the

control animals. This data suggest that neurons in the motor

column are not uniformly affected by the aging process

because morphological changes are proportionally greater in

small neurons than in large neurons.

282. Liu, R. H.; Bertolotto, C.; Engelhardt, J. K.; Chase, M. H. Age-related

changes in soma size of neurons in the spinal cord motor

column of the cat. Neurosci-Lett. 1996 Jun 28; 211(3): 163-6;

ISSN: 0304-3940.

IRELAND. The present study was undertaken to examine the

effect of the aging process on the soma size and number of

motoneurons and interneurons in the motor column of the

spinal cord of old cats. Neurons in the motor column were

divided into small and large populations based on a bimodal

distribution of their soma cross-sectional areas. A 17%

decrease in the cross-sectional area of small neurons was

observed, this decrease was statistically significant (P <

0.0001). The cross-sectional area of large neurons decreased

by only 6%, which was statistically significant (P < 0.05). On

the other hand, there was no significant difference in the

number of large, small or of these combined population of

ventral horn neurons in the aged cats compared with the

control animals. This data suggest that neurons in the motor

column are not uniformly affected by the aging process

because morphological changes are proportionally greater in

small neurons than in large neurons.

283. Logan, S. D.; Pickering, A. E.; Gibson, I. C.; Nolan, M. F.; Spanswick,

D. Electrotonic coupling between rat sympathetic

preganglionic neurones in vitro. J-Physiol-Lond. 1996 Sep 1;

495( Pt 2): 491-502; ISSN: 0022-3751.

ENGLAND. 1. Using the whole-cell recording technique in rat

spinal cord slices we have shown that 26% of sympathetic

preganglionic neurones (SPNs) show spontaneous membrane

potential oscillations. These oscillations consist of trains of

biphasic waves, which we have termed spikelets because of

their similarity to truncated action potentials. 2. The

spikelets were inhibited by TTX and anaesthetics such as

alpha-chloralose but not by the intracellular application of

lidocaine N-ethyl bromide (QX-314). 3. By stimulating the

ventral roots we have demonstrated the presence of short-

latency depolarizations (SLDs) in oscillating neurones. These

SLDs have a similar waveform to the spontaneous spikelets,

and also show the ability to override the frequency of

occurrence of the spontaneous spikelets. These observations

suggest that the spikelets result from electrotonic coupling

between the oscillating SPNs. 4. SLDs were also observed in a

population of non-oscillating, electrotonically coupled,

quiescent SPNs. It was possible to induce oscillations in these

neurones by the injection of depolarizing current (in the

presence of QX-314), suggesting that these neurones are also

gap-junction coupled. 5. Simultaneous whole-cell recordings

were obtained from twenty-three pairs of SPNs. Two pairs

displayed both spontaneous, synchronized oscillations and

action potentials. Electrotonic coupling was confirmed by the

detection of membrane polarization in both neurones in

response to current injected into one neurone. In a further two

pairs of quiescent SPNs, injection of depolarizing current

pulses into one neurone induced action potential discharge in

that neurone and a depolarization and oscillations in the other

neurone. 6. The ability of groups of electrotonically coupled

SPNs to generate spontaneous discharges within the spinal

cord provides a novel mechanism for the integration and

synchronization of information within the sympathetic

nervous system.. 0; 137-58-6; 21306-56-9; 4368-28-9;

7440-70-2.

284. Logan, S. D.; Pickering, A. E.; Gibson, I. C.; Nolan, M. F.; Spanswick,

D. Electrotonic coupling between rat sympathetic

preganglionic neurones in vitro. J-Physiol-Lond. 1996 Sep 1;

495( Pt 2): 491-502; ISSN: 0022-3751.

ENGLAND. 1. Using the whole-cell recording technique in rat

spinal cord slices we have shown that 26% of sympathetic

preganglionic neurones (SPNs) show spontaneous membrane

potential oscillations. These oscillations consist of trains of

biphasic waves, which we have termed spikelets because of

their similarity to truncated action potentials. 2. The

spikelets were inhibited by TTX and anaesthetics such as

alpha-chloralose but not by the intracellular application of

lidocaine N-ethyl bromide (QX-314). 3. By stimulating the

ventral roots we have demonstrated the presence of short-

latency depolarizations (SLDs) in oscillating neurones. These

SLDs have a similar waveform to the spontaneous spikelets,

and also show the ability to override the frequency of

occurrence of the spontaneous spikelets. These observations

suggest that the spikelets result from electrotonic coupling

between the oscillating SPNs. 4. SLDs were also observed in a

population of non-oscillating, electrotonically coupled,

quiescent SPNs. It was possible to induce oscillations in these

neurones by the injection of depolarizing current (in the

presence of QX-314), suggesting that these neurones are also

gap-junction coupled. 5. Simultaneous whole-cell recordings

were obtained from twenty-three pairs of SPNs. Two pairs

displayed both spontaneous, synchronized oscillations and

action potentials. Electrotonic coupling was confirmed by the

detection of membrane polarization in both neurones in

response to current injected into one neurone. In a further two

pairs of quiescent SPNs, injection of depolarizing current

pulses into one neurone induced action potential discharge in

that neurone and a depolarization and oscillations in the other

neurone. 6. The ability of groups of electrotonically coupled

SPNs to generate spontaneous discharges within the spinal

cord provides a novel mechanism for the integration and

synchronization of information within the sympathetic

nervous system.. 0; 137-58-6; 21306-56-9; 4368-28-9;

7440-70-2.

285. Lu, J.; Ebraheim, N. A.; Biyani, A.; Brown, J. A.; Yeasting, R. A.

Vulnerability of great medullary artery. Spine. 1996 Aug 15;

21(16): 1852-5; ISSN: 0362-2436.

UNITED-STATES. STUDY DESIGN: The present study describes

anatomic observations on great medullary artery and

intercostal arteries pertinent to thoracolumbar spinal surgery.

OBJECTIVES: This study reveals the vulnerable course of the

great medullary artery and its relationship to the lateral or

posterolateral approach to thoracic spine. SUMMARY OF

BACKGROUND DATA: There are no previous anatomic data on the

length of the great medullary artery, its intradural course, its

relationship with the anterior spinal artery, and the distance

between two adjacent intercostal arteries. METHODS: The

location of the intercostal arteries was defined, and the

distance between two adjacent arteries was measured at a

point on the lateral surface of the vertebra midway between

its anteroposterior diameter. The intradural length of the

great medullary artery and the angle it formed with the

anterior spinal artery at the point of anastomosis were also

measured. RESULTS: The mean intradural length of the great

medullary artery was 3.6 cm (range, 1.7-8.1 cm), and it passed

over 1-3 disc spaces before joining the anterior spinal artery

at a mean angle of 20.1 degrees (range, 12-28 degrees). The

average distance between two adjacent intercostal arteries

from T6 to L2 was 3.6 cm (range, 2.8-4.0 cm), which provides

a safe window through which a herniated thoracic disc may be

approached if surgery is indicated. CONCLUSIONS: The acute

angle between the great medullary artery and anterior spinal

artery indicates that these two arteries are in close proximity

for considerable length and are liable to be compressed

together with the intervening vascular collaterals by a space-

occupying lesion, such as disc herniation or a fractured

fragment. The longer the intradural course of the great

medullary artery, the more vulnerable it is to compression by

disc herniation or fracture. The intercostal and lumbar

arteries are located at the midportion of the lateral aspect of

the vertebral bodies rather than at the level of intervertebral

discs. Discectomy or decompression of the anterior thoracic

canal may be accomplished through a lateral or posterolateral

extracavitary approach between two intercostal or lumbar

arteries.

286. Lu, J.; Ebraheim, N. A.; Biyani, A.; Brown, J. A.; Yeasting, R. A.

Vulnerability of great medullary artery. Spine. 1996 Aug 15;

21(16): 1852-5; ISSN: 0362-2436.

UNITED-STATES. STUDY DESIGN: The present study describes

anatomic observations on great medullary artery and

intercostal arteries pertinent to thoracolumbar spinal surgery.

OBJECTIVES: This study reveals the vulnerable course of the

great medullary artery and its relationship to the lateral or

posterolateral approach to thoracic spine. SUMMARY OF

BACKGROUND DATA: There are no previous anatomic data on the

length of the great medullary artery, its intradural course, its

relationship with the anterior spinal artery, and the distance

between two adjacent intercostal arteries. METHODS: The

location of the intercostal arteries was defined, and the

distance between two adjacent arteries was measured at a

point on the lateral surface of the vertebra midway between

its anteroposterior diameter. The intradural length of the

great medullary artery and the angle it formed with the

anterior spinal artery at the point of anastomosis were also

measured. RESULTS: The mean intradural length of the great

medullary artery was 3.6 cm (range, 1.7-8.1 cm), and it passed

over 1-3 disc spaces before joining the anterior spinal artery

at a mean angle of 20.1 degrees (range, 12-28 degrees). The

average distance between two adjacent intercostal arteries

from T6 to L2 was 3.6 cm (range, 2.8-4.0 cm), which provides

a safe window through which a herniated thoracic disc may be

approached if surgery is indicated. CONCLUSIONS: The acute

angle between the great medullary artery and anterior spinal

artery indicates that these two arteries are in close proximity

for considerable length and are liable to be compressed

together with the intervening vascular collaterals by a space-

occupying lesion, such as disc herniation or a fractured

fragment. The longer the intradural course of the great

medullary artery, the more vulnerable it is to compression by

disc herniation or fracture. The intercostal and lumbar

arteries are located at the midportion of the lateral aspect of

the vertebral bodies rather than at the level of intervertebral

discs. Discectomy or decompression of the anterior thoracic

canal may be accomplished through a lateral or posterolateral

extracavitary approach between two intercostal or lumbar

arteries.

287. Lubischer, J. L.; Arnold, A. P. Axotomy transiently down-regulates

androgen receptors in motoneurons of the spinal nucleus of the

bulbocavernosus. Brain-Res. 1995 Oct 2; 694(1-2): 61-8; ISSN:

0006-8993.

NETHERLANDS. Testosterone is an important trophic factor for

motoneurons in the spinal nucleus of the bulbocavernosus

(SNB), and SNB motoneurons are more responsive to

testosterone than are other motoneurons. Axonal injury during

early postnatal life prevents the normal development of

steroid-sensitivity by adult SNB motoneurons. Axonal injury

also causes changes in the expression by motoneurons of a

wide range of proteins, including the up-regulation of trophic

factor receptors. We have used a polyclonal antibody (PG-21;

G.S. Prins) to study the expression of androgen receptors in

SNB motoneurons after axonal injury. PG-21 labeled

motoneuronal nuclei in the lower lumbar spinal cord of rats in

a pattern that matched autoradiographic reports of androgen

accumulation in this region of the nervous system. A

population of numerous, small cells located dorsal to the

central canal also showed evidence of androgen receptor

expression. Cutting the axons of SNB motoneurons in adulthood

or in development caused a decrease in androgen receptor

immunoreactivity in SNB motoneurons. This is the first report

that a trophic factor receptor in motoneurons is down-

regulated after axonal injury, and is interesting in light of

reports that testosterone treatment can facilitate

motoneuronal regeneration after nerve cut. Androgen receptor

levels subsequently returned to normal, regardless of the age

at axotomy, providing no evidence for a lasting effect of

developmental axotomy on androgen receptor levels in SNB

motoneurons. Thus, axotomy-induced down-regulation of

androgen receptors does not underlie the inability of SNB

motoneurons to respond to androgen treatment several months

after pudendal nerve cut in development.. 0.

288. Lubischer, J. L.; Arnold, A. P. Axotomy transiently down-regulates

androgen receptors in motoneurons of the spinal nucleus of the

bulbocavernosus. Brain-Res. 1995 Oct 2; 694(1-2): 61-8; ISSN:

0006-8993.

NETHERLANDS. Testosterone is an important trophic factor for

motoneurons in the spinal nucleus of the bulbocavernosus

(SNB), and SNB motoneurons are more responsive to

testosterone than are other motoneurons. Axonal injury during

early postnatal life prevents the normal development of

steroid-sensitivity by adult SNB motoneurons. Axonal injury

also causes changes in the expression by motoneurons of a

wide range of proteins, including the up-regulation of trophic

factor receptors. We have used a polyclonal antibody (PG-21;

G.S. Prins) to study the expression of androgen receptors in

SNB motoneurons after axonal injury. PG-21 labeled

motoneuronal nuclei in the lower lumbar spinal cord of rats in

a pattern that matched autoradiographic reports of androgen

accumulation in this region of the nervous system. A

population of numerous, small cells located dorsal to the

central canal also showed evidence of androgen receptor

expression. Cutting the axons of SNB motoneurons in adulthood

or in development caused a decrease in androgen receptor

immunoreactivity in SNB motoneurons. This is the first report

that a trophic factor receptor in motoneurons is down-

regulated after axonal injury, and is interesting in light of

reports that testosterone treatment can facilitate

motoneuronal regeneration after nerve cut. Androgen receptor

levels subsequently returned to normal, regardless of the age

at axotomy, providing no evidence for a lasting effect of

developmental axotomy on androgen receptor levels in SNB

motoneurons. Thus, axotomy-induced down-regulation of

androgen receptors does not underlie the inability of SNB

motoneurons to respond to androgen treatment several months

after pudendal nerve cut in development.. 0.

289. Lukashin, A. V.; Amirikian, B. R.; Georgopoulos, A. P. Neural

computations underlying the exertion of force: a model. Biol-

Cybern. 1996 May; 74(5): 469-78; ISSN: 0340-1200.

GERMANY. We have developed a model that simulates possible

mechanisms by which supraspinal neuronal signals coding

forces could converge in the spinal cord and provide an ongoing

integrated signal to the motoneuronal pools whose activation

results in the exertion of force. The model consists of a three-

layered neural network connected to a two-joint-six-muscle

model of the arm. The network layers represent supraspinal

populations, spinal cord interneurons, and motoneuronal pools.

We propose an approach to train the network so that, after the

synaptic connections between the layers are adjusted, the

performance of the model is consistent with experimental

data obtained on different organisms using different

experimental paradigms: the stiffness characteristics of

human arm; the structure of force fields generated by the

stimulation of the frog's spinal cord; and a correlation

between motor cortical activity and force exerted by monkey

against an immovable object. The model predicts a specific

pattern of connections between supraspinal populations coding

forces and spinal cord interneurons: the weight of connection

should be correlated with directional preference of

interconnected units. Finally, our simulations demonstrate

that the force generated by the sum of neural signals can be

nearly equal to the vector sum of forces generated by each

signal independently, in spite of the complex nonlinearities

intervening between supraspinal commands and forces exerted

by the arm in response to these commands.

290. Lukashin, A. V.; Amirikian, B. R.; Georgopoulos, A. P. Neural

computations underlying the exertion of force: a model. Biol-

Cybern. 1996 May; 74(5): 469-78; ISSN: 0340-1200.

GERMANY. We have developed a model that simulates possible

mechanisms by which supraspinal neuronal signals coding

forces could converge in the spinal cord and provide an ongoing

integrated signal to the motoneuronal pools whose activation

results in the exertion of force. The model consists of a three-

layered neural network connected to a two-joint-six-muscle

model of the arm. The network layers represent supraspinal

populations, spinal cord interneurons, and motoneuronal pools.

We propose an approach to train the network so that, after the

synaptic connections between the layers are adjusted, the

performance of the model is consistent with experimental

data obtained on different organisms using different

experimental paradigms: the stiffness characteristics of

human arm; the structure of force fields generated by the

stimulation of the frog's spinal cord; and a correlation

between motor cortical activity and force exerted by monkey

against an immovable object. The model predicts a specific

pattern of connections between supraspinal populations coding

forces and spinal cord interneurons: the weight of connection

should be correlated with directional preference of

interconnected units. Finally, our simulations demonstrate

that the force generated by the sum of neural signals can be

nearly equal to the vector sum of forces generated by each

signal independently, in spite of the complex nonlinearities

intervening between supraspinal commands and forces exerted

by the arm in response to these commands.

291. Lumsden, A.; Krumlauf, R. Patterning the vertebrate neuraxis.

Science. 1996 Nov 15; 274(5290): 1109-15; ISSN: 0036-8075.

UNITED-STATES. Neuraxial patterning is a continuous process

that extends over a protracted period of development. During

gastrulation a crude anteroposterior pattern, detectable by

molecular markers, is conferred on the neuroectoderm by

signals from the endomesoderm that are largely inseparable

from those of neural induction itself. This coarse-grained

pattern is subsequently reinforced and refined by diverse,

locally acting mechanisms. Segmentation and long-range

signaling from organizing centers are prominent among the

emerging principles governing regional pattern.. 302-79-4.

292. Lumsden, A.; Krumlauf, R. Patterning the vertebrate neuraxis.

Science. 1996 Nov 15; 274(5290): 1109-15; ISSN: 0036-8075.

UNITED-STATES. Neuraxial patterning is a continuous process

that extends over a protracted period of development. During

gastrulation a crude anteroposterior pattern, detectable by

molecular markers, is conferred on the neuroectoderm by

signals from the endomesoderm that are largely inseparable

from those of neural induction itself. This coarse-grained

pattern is subsequently reinforced and refined by diverse,

locally acting mechanisms. Segmentation and long-range

signaling from organizing centers are prominent among the

emerging principles governing regional pattern.. 302-79-4.

293. Luo, L.; Wiesenfeld Hallin, Z. Differential effects of pre-

treatment with intrathecal or intravenous morphine on the

prevention of spinal cord hyperexcitability following sciatic

nerve section in the rat. Acta-Anaesthesiol-Scand. 1996 Jan;

40(1): 91-5; ISSN: 0001-5172.

DENMARK. The effect of intrathecal (i.t.) and intravenous (i.v.)

morphine on spinal hyperexcitability following unilateral

section of the sciatic nerve was studied in decerebrate,

spinalized, unanesthetized rats. Sciatic nerve section evoked a

biphasic, prolonged hyperexcitability of the flexor reflex.

Either i.v. (0.2, 1 or 10 mg center dot kg-1) or i.t. (3 or 10 mu

g) morphine was administered prior to sciatic nerve section.

All doses of morphine significantly depressed the baseline

flexor reflex and abolished the less intense prolonged second

component of reflex hyperexcitability. One and 10, but not 0.2,

mg center dot kg-1 i.v. morphine significantly depressed the

first phase of spinal cord sensitization. However, both 3 mu g

and 10 mu g i.t. morphine were significantly more effective

than i.v. morphine in suppressing spinal cord hyperexcitability.

The present results suggest that moderate doses of i.t.

morphine decrease spinal hyperexcitability following nerve

transection more than even extremely large i.v. doses. The

poorer effect of i.v. morphine on preventing spinal

hyperexcitability may be due to low spinal concentration after

systemic administration.. 0; 57-27-2.

294. Luo, L.; Wiesenfeld Hallin, Z. Differential effects of pre-

treatment with intrathecal or intravenous morphine on the

prevention of spinal cord hyperexcitability following sciatic

nerve section in the rat. Acta-Anaesthesiol-Scand. 1996 Jan;

40(1): 91-5; ISSN: 0001-5172.

DENMARK. The effect of intrathecal (i.t.) and intravenous (i.v.)

morphine on spinal hyperexcitability following unilateral

section of the sciatic nerve was studied in decerebrate,

spinalized, unanesthetized rats. Sciatic nerve section evoked a

biphasic, prolonged hyperexcitability of the flexor reflex.

Either i.v. (0.2, 1 or 10 mg center dot kg-1) or i.t. (3 or 10 mu

g) morphine was administered prior to sciatic nerve section.

All doses of morphine significantly depressed the baseline

flexor reflex and abolished the less intense prolonged second

component of reflex hyperexcitability. One and 10, but not 0.2,

mg center dot kg-1 i.v. morphine significantly depressed the

first phase of spinal cord sensitization. However, both 3 mu g

and 10 mu g i.t. morphine were significantly more effective

than i.v. morphine in suppressing spinal cord hyperexcitability.

The present results suggest that moderate doses of i.t.

morphine decrease spinal hyperexcitability following nerve

transection more than even extremely large i.v. doses. The

poorer effect of i.v. morphine on preventing spinal

hyperexcitability may be due to low spinal concentration after

systemic administration.. 0; 57-27-2.

295. Mannion, R. J.; Doubell, T. P.; Coggeshall, R. E.; Woolf, C. J.

Collateral sprouting of uninjured primary afferent A-fibers

into the superficial dorsal horn of the adult rat spinal cord

after topical capsaicin treatment to the sciatic nerve. J-

Neurosci. 1996 Aug 15; 16(16): 5189-95; ISSN: 0270-6474.

UNITED-STATES. That terminals of uninjured primary sensory

neurons terminating in the dorsal horn of the spinal cord can

collaterally sprout was first suggested by Liu and Chambers

(1958), but this has since been disputed. Recently, horseradish

peroxidase conjugated to the B subunit of cholera toxin (B-

HRP) and intracellular HRP injections have shown that sciatic

nerve section or crush produces a long-lasting rearrangement

in the organization of primary afferent central terminals, with

A-fibers sprouting into lamina II, a region that normally

receives only C-fiber input (Woolf et al., 1992). The

mechanism of this A-fiber sprouting has been thought to

involve injury-induced C-fiber transganglionic degeneration

combined with myelinated A-fibers being conditioned into a

regenerative growth state. In this study, we ask whether C-

fiber degeneration and A-fiber conditioning are both necessary

for the sprouting of A-fibers into lamina II. Local application

of the C-fiber-specific neurotoxin capsaicin to the sciatic

nerve has previously been shown to result in C-fiber damage

and degenerative atrophy in lamina II. We have used B-HRP to

transganglionically label A-fiber central terminals and have

shown that 2 weeks after topical capsaicin treatment to the

sciatic nerve, the pattern of B-HRP staining in the dorsal horn

is indistinguishable from that seen after axotomy, with lamina

II displaying novel staining in the identical region containing

capsaicin-treated C-fiber central terminals. These results

suggest that after C-fiber injury, uninjured A-fiber central

terminals can collaterally sprout into lamina II of the dorsal

horn. This phenomenon may help to explain the pain associated

with C-fiber neuropathy.. EC 1.11.1.-; EC 3.1.3; EC 3.1.3.-; 0;

404-86-4; 9012-63-9.

296. Mannion, R. J.; Doubell, T. P.; Coggeshall, R. E.; Woolf, C. J.

Collateral sprouting of uninjured primary afferent A-fibers

into the superficial dorsal horn of the adult rat spinal cord

after topical capsaicin treatment to the sciatic nerve. J-

Neurosci. 1996 Aug 15; 16(16): 5189-95; ISSN: 0270-6474.

UNITED-STATES. That terminals of uninjured primary sensory

neurons terminating in the dorsal horn of the spinal cord can

collaterally sprout was first suggested by Liu and Chambers

(1958), but this has since been disputed. Recently, horseradish

peroxidase conjugated to the B subunit of cholera toxin (B-

HRP) and intracellular HRP injections have shown that sciatic

nerve section or crush produces a long-lasting rearrangement

in the organization of primary afferent central terminals, with

A-fibers sprouting into lamina II, a region that normally

receives only C-fiber input (Woolf et al., 1992). The

mechanism of this A-fiber sprouting has been thought to

involve injury-induced C-fiber transganglionic degeneration

combined with myelinated A-fibers being conditioned into a

regenerative growth state. In this study, we ask whether C-

fiber degeneration and A-fiber conditioning are both necessary

for the sprouting of A-fibers into lamina II. Local application

of the C-fiber-specific neurotoxin capsaicin to the sciatic

nerve has previously been shown to result in C-fiber damage

and degenerative atrophy in lamina II. We have used B-HRP to

transganglionically label A-fiber central terminals and have

shown that 2 weeks after topical capsaicin treatment to the

sciatic nerve, the pattern of B-HRP staining in the dorsal horn

is indistinguishable from that seen after axotomy, with lamina

II displaying novel staining in the identical region containing

capsaicin-treated C-fiber central terminals. These results

suggest that after C-fiber injury, uninjured A-fiber central

terminals can collaterally sprout into lamina II of the dorsal

horn. This phenomenon may help to explain the pain associated

with C-fiber neuropathy.. EC 1.11.1.-; EC 3.1.3; EC 3.1.3.-; 0;

404-86-4; 9012-63-9.

297. Mansikka, H.; Idanpaan Heikkila, J. J.; Pertovaara, A. Different

roles of alpha 2-adrenoceptors of the medulla versus the

spinal cord in modulation of mustard oil-induced central

hyperalgesia in rats. Eur-J-Pharmacol. 1996 Feb 15; 297(1-2):

19-26; ISSN: 0014-2999.

NETHERLANDS. We attempted to determine the roles of spinal

versus medullary alpha 2-adrenoceptors in modulation of

central hyperalgesia in rats. Central hyperalgesia was

produced by applying mustard oil (50%) to the skin of the ankle

of one hindpaw. The threshold for eliciting a hindlimb flexion

reflex was determined by applying a series of calibrated

monofilaments to the glabrous skin of the hindpaw

contralaterally (= control) or ipsilaterally to the mustard oil-

treated ankle (= outside the area of primary hyperalgesia).

Medetomidine (an alpha 2-adrenoceptor agonist; 1

micrograms), atipamezole (an alpha 2-adrenoceptor

antagonist; 2.5 micrograms) or saline was microinjected into

the lateral reticular nucleus of the medulla, the nucleus raphe

magnus, or intrathecally to the lumbar spinal cord 12 min

before the mustard oil treatment. Following saline injections,

mustard oil produced a significant decrease of the hindlimb

withdrawal threshold in the mustard oil-treated limb but not

in the contralateral limb. Atipamezole in the lateral reticular

nucleus produced a complete reversal of the hyperalgesia but

no effect on the threshold of the intact limb. However,

atipamezole in the raphe magnus nucleus or in the lumbar

spinal cord did not produce a significant attenuation of the

hyperalgesia. Medetomidine in the spinal cord, but not in the

lateral reticular nucleus, reversed the hyperalgesia. At this

dose range (up to 3 micrograms), medetomidine in the spinal

cord of nonhyperalgesic control rats did not produce any

significant change in the withdrawal response of hindlimbs or

in the tail-flick latency. The results indicate that neurogenic

inflammation induces significant plastic changes in the

function of alpha 2-adrenergic pain regulatory mechanisms. In

rats with mustard oil-induced central hyperalgesia, an alpha

2-adrenoceptor antagonist produces an antihyperalgesic effect

due to an action on the caudal ventrolateral medulla, whereas

an alpha 2-adrenoceptor agonist produces an enhanced

antinociceptive effect due to a direct action on the spinal

cord.. 0; 0; 0; 0; 0; 0; 104054-27-5; 8007-40-7; 86347-14-0.

298. Mansikka, H.; Idanpaan Heikkila, J. J.; Pertovaara, A. Different

roles of alpha 2-adrenoceptors of the medulla versus the

spinal cord in modulation of mustard oil-induced central

hyperalgesia in rats. Eur-J-Pharmacol. 1996 Feb 15; 297(1-2):

19-26; ISSN: 0014-2999.

NETHERLANDS. We attempted to determine the roles of spinal

versus medullary alpha 2-adrenoceptors in modulation of

central hyperalgesia in rats. Central hyperalgesia was

produced by applying mustard oil (50%) to the skin of the ankle

of one hindpaw. The threshold for eliciting a hindlimb flexion

reflex was determined by applying a series of calibrated

monofilaments to the glabrous skin of the hindpaw

contralaterally (= control) or ipsilaterally to the mustard oil-

treated ankle (= outside the area of primary hyperalgesia).

Medetomidine (an alpha 2-adrenoceptor agonist; 1

micrograms), atipamezole (an alpha 2-adrenoceptor

antagonist; 2.5 micrograms) or saline was microinjected into

the lateral reticular nucleus of the medulla, the nucleus raphe

magnus, or intrathecally to the lumbar spinal cord 12 min

before the mustard oil treatment. Following saline injections,

mustard oil produced a significant decrease of the hindlimb

withdrawal threshold in the mustard oil-treated limb but not

in the contralateral limb. Atipamezole in the lateral reticular

nucleus produced a complete reversal of the hyperalgesia but

no effect on the threshold of the intact limb. However,

atipamezole in the raphe magnus nucleus or in the lumbar

spinal cord did not produce a significant attenuation of the

hyperalgesia. Medetomidine in the spinal cord, but not in the

lateral reticular nucleus, reversed the hyperalgesia. At this

dose range (up to 3 micrograms), medetomidine in the spinal

cord of nonhyperalgesic control rats did not produce any

significant change in the withdrawal response of hindlimbs or

in the tail-flick latency. The results indicate that neurogenic

inflammation induces significant plastic changes in the

function of alpha 2-adrenergic pain regulatory mechanisms. In

rats with mustard oil-induced central hyperalgesia, an alpha

2-adrenoceptor antagonist produces an antihyperalgesic effect

due to an action on the caudal ventrolateral medulla, whereas

an alpha 2-adrenoceptor agonist produces an enhanced

antinociceptive effect due to a direct action on the spinal

cord.. 0; 0; 0; 0; 0; 0; 104054-27-5; 8007-40-7; 86347-14-0.

299. Marin, O.; Smeets, W. J.; Gonzalez, A. Do amphibians have a true

locus coeruleus? Neuroreport. 1996 May 31; 7(8): 1447-51;

ISSN: 0959-4965.

ENGLAND. Much controversy surrounds the identity of a locus

coeruleus in amphibians because although previous studies on

the isthmic region of the brain of anurans and urodeles

revealed the presence of noradrenergic cell bodies they failed

to demonstrate their projection to the telencephalon or the

spinal cord. In the present study applications of Texas Red-

conjugated dextran amines to the basal telencephalon or to the

spinal cord in combination with tyrosine hydroxylase

immunohistochemistry revealed that the noradrenergic cell

bodies in the isthmic region of anuran (Rana perezi) and

urodele (Pleurodeles waltl) amphibians project to the

telencephalon as well as to the spinal cord. On the basis of

location, neurotransmitter content and efferent projections,

the isthmic noradrenergic cell group of amphibians is,

therefore, considered homologous to the locus coeruleus of

amniotes.

300. Marin, O.; Smeets, W. J.; Gonzalez, A. Do amphibians have a true

locus coeruleus? Neuroreport. 1996 May 31; 7(8): 1447-51;

ISSN: 0959-4965.

ENGLAND. Much controversy surrounds the identity of a locus

coeruleus in amphibians because although previous studies on

the isthmic region of the brain of anurans and urodeles

revealed the presence of noradrenergic cell bodies they failed

to demonstrate their projection to the telencephalon or the

spinal cord. In the present study applications of Texas Red-

conjugated dextran amines to the basal telencephalon or to the

spinal cord in combination with tyrosine hydroxylase

immunohistochemistry revealed that the noradrenergic cell

bodies in the isthmic region of anuran (Rana perezi) and

urodele (Pleurodeles waltl) amphibians project to the

telencephalon as well as to the spinal cord. On the basis of

location, neurotransmitter content and efferent projections,

the isthmic noradrenergic cell group of amphibians is,

therefore, considered homologous to the locus coeruleus of

amniotes.

301. Marsh, A. E.; Barr, B. C.; Madigan, J.; Lakritz, J.; Nordhausen, R.;

Conrad, P. A. Neosporosis as a cause of equine protozoal

myeloencephalitis. J-Am-Vet-Med-Assoc. 1996 Dec 1;

209(11): 1907-13; ISSN: 0003-1488.

UNITED-STATES. Neosporosis was diagnosed in an 11-year-old

Quarter Horse gelding with clinical signs and diagnostic test

results compatible with equine protozoal myeloencephalitis

(EPM). Presumptive postmortem diagnosis of EPM attributable

to Sarcocystis neurona infection is generally made on the

basis of detecting an antibody titer to S neurona in the CSF or

characteristic histologic lesions, even when parasites have

not been specifically identified. Neosporosis was confirmed in

the horse described here by use of immunohistochemical

examination, in vitro culturing, and ultrastructural and

molecular characterization of parasites from infected tissues.

Antibody testing of serum and CSF samples indicated that

Neospora-specific anti-bodies can react with S neurona

proteins on western blot analysis. The confirmation that

neosporosis in horses can mimic EPM emphasizes the need to

broaden the etiologic definition of EPM beyond infections

exclusively attributable to S neurona.. 0; 0.

302. Marsh, A. E.; Barr, B. C.; Madigan, J.; Lakritz, J.; Nordhausen, R.;

Conrad, P. A. Neosporosis as a cause of equine protozoal

myeloencephalitis. J-Am-Vet-Med-Assoc. 1996 Dec 1;

209(11): 1907-13; ISSN: 0003-1488.

UNITED-STATES. Neosporosis was diagnosed in an 11-year-old

Quarter Horse gelding with clinical signs and diagnostic test

results compatible with equine protozoal myeloencephalitis

(EPM). Presumptive postmortem diagnosis of EPM attributable

to Sarcocystis neurona infection is generally made on the

basis of detecting an antibody titer to S neurona in the CSF or

characteristic histologic lesions, even when parasites have

not been specifically identified. Neosporosis was confirmed in

the horse described here by use of immunohistochemical

examination, in vitro culturing, and ultrastructural and

molecular characterization of parasites from infected tissues.

Antibody testing of serum and CSF samples indicated that

Neospora-specific anti-bodies can react with S neurona

proteins on western blot analysis. The confirmation that

neosporosis in horses can mimic EPM emphasizes the need to

broaden the etiologic definition of EPM beyond infections

exclusively attributable to S neurona.. 0; 0.

303. Massaquoi, S. G.; Slotine, J. J. The intermediate cerebellum may

function as a wave-variable processor. Neurosci-Lett. 1996

Aug 30; 215(1): 60-4; ISSN: 0304-3940.

IRELAND. A newly developed model suggests that the

intermediate cerebellum and spinal cord gray matter may

contribute to movement control by processing control signals

as wave variables. Within specialized communication systems,

wave variables are combinations of forward and return signals

that ensure stable exchange between two sites despite

transmission delays. The composition of signals transmitted

in the ventral spinocerebellar tract appears to be consistent

with that of a wave variable, and computer simulations of the

model yield signals similar to those observed in the monkey

interpositus nucleus. Wave-variable communication may

enable the animal motor system to maintain stable, high-

performance feedback control in the presence of potentially

destabilizing signal transmission delays.

304. Massaquoi, S. G.; Slotine, J. J. The intermediate cerebellum may

function as a wave-variable processor. Neurosci-Lett. 1996

Aug 30; 215(1): 60-4; ISSN: 0304-3940.

IRELAND. A newly developed model suggests that the

intermediate cerebellum and spinal cord gray matter may

contribute to movement control by processing control signals

as wave variables. Within specialized communication systems,

wave variables are combinations of forward and return signals

that ensure stable exchange between two sites despite

transmission delays. The composition of signals transmitted

in the ventral spinocerebellar tract appears to be consistent

with that of a wave variable, and computer simulations of the

model yield signals similar to those observed in the monkey

interpositus nucleus. Wave-variable communication may

enable the animal motor system to maintain stable, high-

performance feedback control in the presence of potentially

destabilizing signal transmission delays.

305. Matesz, C.; Szekely, G. Organization of the ambiguus nucleus in

the frog (Rana esculenta). J-Comp-Neurol. 1996 Jul 22; 371(2):

258-69; ISSN: 0021-9967.

UNITED-STATES. The common root of the glossopharyngeal,

vagal, and accessory nerves and the individual branches of the

vagus complex were labeled with cobalt, and the organization

of the ambiguus nucleus was studied. The cell column labeled

through the common root extended from the upper part of the

medulla to the rostral spinal cord over a distance of about

3,500 microns. The labeling of individual branches revealed

four subdivisions. 1) The pharyngomotor subdivision occupied

the rostral 800 microns of the cell column. It gave origin to

the innervation of the pharyngeal muscles. 2) The visceromotor

subdivision, consisting of small and medium-sized cells

labeled by way of the visceral branches of the vagus, was

found in the rostrocaudal extent of the medulla. 3) the

laryngomotor subdivision extended in the obex region over a

distance of more than 1,000 microns. It supplied the sphincter

muscles of the larynx. The dilator laryngeal muscle was

represented in the rostral part of the visceromotor

subdivision. 4) The accessory nerve subdivision was located in

the lower medulla and the rostral spinal cord. From the

results, the following conclusions are drawn. 1) The basic

organization of the frog ambiguus nucleus is comparable to

that of the rat, differences in nuclear organization reflecting

differences in peripheral structures. 2) The cytoarchitectonic

structure of the four subdivisions innervating different

peripheral targets characteristically differ from each other.

3) On the basis of its characteristic neuronal morphology, the

accessory nerve nucleus is regarded as an independent

structure.

306. Matesz, C.; Szekely, G. Organization of the ambiguus nucleus in

the frog (Rana esculenta). J-Comp-Neurol. 1996 Jul 22; 371(2):

258-69; ISSN: 0021-9967.

UNITED-STATES. The common root of the glossopharyngeal,

vagal, and accessory nerves and the individual branches of the

vagus complex were labeled with cobalt, and the organization

of the ambiguus nucleus was studied. The cell column labeled

through the common root extended from the upper part of the

medulla to the rostral spinal cord over a distance of about

3,500 microns. The labeling of individual branches revealed

four subdivisions. 1) The pharyngomotor subdivision occupied

the rostral 800 microns of the cell column. It gave origin to

the innervation of the pharyngeal muscles. 2) The visceromotor

subdivision, consisting of small and medium-sized cells

labeled by way of the visceral branches of the vagus, was

found in the rostrocaudal extent of the medulla. 3) the

laryngomotor subdivision extended in the obex region over a

distance of more than 1,000 microns. It supplied the sphincter

muscles of the larynx. The dilator laryngeal muscle was

represented in the rostral part of the visceromotor

subdivision. 4) The accessory nerve subdivision was located in

the lower medulla and the rostral spinal cord. From the

results, the following conclusions are drawn. 1) The basic

organization of the frog ambiguus nucleus is comparable to

that of the rat, differences in nuclear organization reflecting

differences in peripheral structures. 2) The cytoarchitectonic

structure of the four subdivisions innervating different

peripheral targets characteristically differ from each other.

3) On the basis of its characteristic neuronal morphology, the

accessory nerve nucleus is regarded as an independent

structure.

307. Matsumoto, A.; Arai, Y.; Prins, G. S. Androgenic regulation of

androgen receptor immunoreactivity in motoneurons of the

spinal nucleus of the bulbocavernosus of male rats. J-

Neuroendocrinol. 1996 Jul; 8(7): 553-9; ISSN: 0953-8194.

ENGLAND. Androgenic regulation of androgen receptor (AR)

immunoreactivity was examined in androgen-sensitive

motoneurons of the spinal nucleus of the bulbocavernosus

(SNB) in adult male rats by immunohistochemistry using the

polyclonal antibody, PG21. In intact controls, intense AR

immunoreactivity was confined to the cell nucleus, but not in

the nucleolus of SNB motoneurons, whereas cytoplasmic AR

immunoreactivity was weak. Androgen withdrawal

significantly reduced both the intensity of AR

immunoreactivity in the nuclei and number of AR

immunoreactive nuclei of the SNB motoneurons within 1 day of

castration. AR immunostaining in the nucleus and cytoplasm

was completely eliminated 5 or 10 days following castration.

These changes were prevented by replacement of testosterone

propionate (TP). The number of AR immunoreactive nuclei

recovered to about half of the control levels within 20 min or

1 hr of TP administration to males 5 days after castration,

although the intensity of AR immunoreactivity was almost the

same as that of males 1 day following castration. Both the

intensity of nuclear and cytoplasmic AR immunoreactivity and

number of AR immunoreactive nuclei recovered to the control

levels 2 or 6 hr after TP injection. These results suggest that

androgen causes a significant up-regulation in AR expression

of SNB motoneurons.. 0; 0; 57-85-2.

308. Matsumoto, A.; Arai, Y.; Prins, G. S. Androgenic regulation of

androgen receptor immunoreactivity in motoneurons of the

spinal nucleus of the bulbocavernosus of male rats. J-

Neuroendocrinol. 1996 Jul; 8(7): 553-9; ISSN: 0953-8194.

ENGLAND. Androgenic regulation of androgen receptor (AR)

immunoreactivity was examined in androgen-sensitive

motoneurons of the spinal nucleus of the bulbocavernosus

(SNB) in adult male rats by immunohistochemistry using the

polyclonal antibody, PG21. In intact controls, intense AR

immunoreactivity was confined to the cell nucleus, but not in

the nucleolus of SNB motoneurons, whereas cytoplasmic AR

immunoreactivity was weak. Androgen withdrawal

significantly reduced both the intensity of AR

immunoreactivity in the nuclei and number of AR

immunoreactive nuclei of the SNB motoneurons within 1 day of

castration. AR immunostaining in the nucleus and cytoplasm

was completely eliminated 5 or 10 days following castration.

These changes were prevented by replacement of testosterone

propionate (TP). The number of AR immunoreactive nuclei

recovered to about half of the control levels within 20 min or

1 hr of TP administration to males 5 days after castration,

although the intensity of AR immunoreactivity was almost the

same as that of males 1 day following castration. Both the

intensity of nuclear and cytoplasmic AR immunoreactivity and

number of AR immunoreactive nuclei recovered to the control

levels 2 or 6 hr after TP injection. These results suggest that

androgen causes a significant up-regulation in AR expression

of SNB motoneurons.. 0; 0; 57-85-2.

309. Matsuzaki, H.; Wakabayashi, K.; Ishihara, K.; Ishikawa, H.;

Kawabata, H.; Onomura, T. The origin and significance of spinal

cord pulsation. Spinal-Cord. 1996 Jul; 34(7): 422-6; ISSN:

1362-4393.

ENGLAND. We studied the origin and mechanism of spinal cord

pulsation in ten dogs in order to elucidate its clinical

significance. Under general anesthesia, a 6 cm length of the

animals' cervical spinal cord was exposed and the

cerebrospinal fluid removed. The amplitude of spinal pulsation

was then measured by means of ultrasonography in Mode M. The

measurements were made after the spinal cord was cut: (1) on

the cranial side; (2) on the cranial as well as caudal side, with

the nerve roots and radicular arteries intact; (3) on both sides

as in (2), which was then supplemented with the severance of

the nerve roots and radicular arteries. It was demonstrated

that, while the pulsation amplitude stood at an average of 88.0

microns before the surgical treatment, it rose to 455.0

microns in (1) and 274.8 microns in (2), but dropped to nearly

zero in (3). The 5.2-fold increase in pulsation following the

cordotomy on the cranial side was attributed to two factors:

(1) the increased spinal mobility due to the cordotomy; (2) the

elevation of blood pressure. The results of the three different

degrees of spinal detachment suggested that spinal pulsation

derived mainly from the radicular arteries and that its

presence indicated low tonicity in the spinal cord and

favorable circulation in the radicular arteries.

310. Matsuzaki, H.; Wakabayashi, K.; Ishihara, K.; Ishikawa, H.;

Kawabata, H.; Onomura, T. The origin and significance of spinal

cord pulsation. Spinal-Cord. 1996 Jul; 34(7): 422-6; ISSN:

1362-4393.

ENGLAND. We studied the origin and mechanism of spinal cord

pulsation in ten dogs in order to elucidate its clinical

significance. Under general anesthesia, a 6 cm length of the

animals' cervical spinal cord was exposed and the

cerebrospinal fluid removed. The amplitude of spinal pulsation

was then measured by means of ultrasonography in Mode M. The

measurements were made after the spinal cord was cut: (1) on

the cranial side; (2) on the cranial as well as caudal side, with

the nerve roots and radicular arteries intact; (3) on both sides

as in (2), which was then supplemented with the severance of

the nerve roots and radicular arteries. It was demonstrated

that, while the pulsation amplitude stood at an average of 88.0

microns before the surgical treatment, it rose to 455.0

microns in (1) and 274.8 microns in (2), but dropped to nearly

zero in (3). The 5.2-fold increase in pulsation following the

cordotomy on the cranial side was attributed to two factors:

(1) the increased spinal mobility due to the cordotomy; (2) the

elevation of blood pressure. The results of the three different

degrees of spinal detachment suggested that spinal pulsation

derived mainly from the radicular arteries and that its

presence indicated low tonicity in the spinal cord and

favorable circulation in the radicular arteries.

311. Mazzone, P.; Pisani, R.; Nobili, F.; Arrigo, A.; Gambaro, M.;

Rodriguez, G. Assessment of regional cerebral blood flow

during spinal cord stimulation in humans. Stereotact-Funct-

Neurosurg. 1995; 64(4): 197-201; ISSN: 1011-6125.

SWITZERLAND. Increased cerebral perfusion has been reported

in both animal models and humans undergoing spinal cord

stimulation (SCS). However, this was an inconsistent finding

and variables able to influence regional cerebral blood flow

(rCBF) following SCS are poorly investigated. We report our

experience on rCBF measurements by the xenon-133 inhalation

technique in 20 patients receiving acute and chronic SCS for

different pathologies in basal conditions. Neither acute nor

chronic SCS induced significant rCBF changes in the group of

patients as a whole. However females, non-atherosclerotic

patients and patients with a cervical SCS lead, showed a trend

(borderline statistical significance) toward a redistribution of

rCBF with increased values in frontoprerolandic and decreased

values in postrolandic regions. Although SCS appears to

influence intracerebral distribution more than absolute

changes in blood flow, the mechanisms underlying such a

phenomenon remain unknown. Functional activation of frontal

lobes by the ascending reticular pathways through the

thalamofrontal projections could be one possible hypothesis

which has to be confirmed by further studies.. 0.

312. Mazzone, P.; Pisani, R.; Nobili, F.; Arrigo, A.; Gambaro, M.;

Rodriguez, G. Assessment of regional cerebral blood flow

during spinal cord stimulation in humans. Stereotact-Funct-

Neurosurg. 1995; 64(4): 197-201; ISSN: 1011-6125.

SWITZERLAND. Increased cerebral perfusion has been reported

in both animal models and humans undergoing spinal cord

stimulation (SCS). However, this was an inconsistent finding

and variables able to influence regional cerebral blood flow

(rCBF) following SCS are poorly investigated. We report our

experience on rCBF measurements by the xenon-133 inhalation

technique in 20 patients receiving acute and chronic SCS for

different pathologies in basal conditions. Neither acute nor

chronic SCS induced significant rCBF changes in the group of

patients as a whole. However females, non-atherosclerotic

patients and patients with a cervical SCS lead, showed a trend

(borderline statistical significance) toward a redistribution of

rCBF with increased values in frontoprerolandic and decreased

values in postrolandic regions. Although SCS appears to

influence intracerebral distribution more than absolute

changes in blood flow, the mechanisms underlying such a

phenomenon remain unknown. Functional activation of frontal

lobes by the ascending reticular pathways through the

thalamofrontal projections could be one possible hypothesis

which has to be confirmed by further studies.. 0.

313. McCarson, K. E.; Krause, J. E. The neurokinin-1 receptor antagonist

LY306,740 blocks nociception-induced increases in dorsal horn

neurokinin-1 receptor gene expression. Mol-Pharmacol. 1996

Nov; 50(5): 1189-99; ISSN: 0026-895X.

UNITED-STATES. Dilute formalin injected into the rat hindpaw

as a nociceptive stimulus increases neurokinin-1 receptor

(NK-1R) mRNA levels in the dorsal horn of the spinal cord.

Increased NK-1R mRNA levels could result from increased

mRNA stability or an increased rate of NK-1R mRNA

transcription. In this study, RNA samples prepared from the

spinal cords of rats receiving an injection of formalin into the

right hindpaw were assayed for NK-1R mRNA with the use of

solution hybridization-nuclease protection assays. The mature

and incompletely spliced NK-1R-encoding RNAs protected by

endogenous rat RNAs were characterized by the use of NK-1R

plasmid constructs containing intron sequences. NK-1R pre-

mRNA species were enriched in the nuclear fractions of spinal

cord samples, and in the steady state, total molar amounts of

NK-1R pre-mRNAs were 2-fold greater than those of mature

NK-1R mRNA. In formalin-treated animals, the temporal

pattern of peak pre-mRNA levels compared with mature mRNA

indicated that chemogenic nociception either activates

transcription of the NK-1R gene or decreases the rate of pre-

mRNA splicing. In the ipsilateral lumbar dorsal hom, NK-1R

mRNA levels were significantly increased at 2 and 6 hr after

formalin injection. Levels of the NK-1R pre-mRNA containing

both introns A and B were significantly increased 1 hr after

formalin treatment, and levels of NK-1R pre-mRNAs containing

intron A were significantly elevated at 2 hr after formalin

treatment. Pretreatment of rats with the selective NK-1R

antagonist LY306,740 was used to determine the role of NK-1R

activation in the regulation of nociception-induced NK-1R

mRNA levels. Rats were pretreated with either LY306,740 or

LY307,679 (an inactive enantiomer) before injection of

formalin into the right hindpaw. Pretreatment with LY306,740

(but not LY307,679) completely blocked the formalin-induced

increase in dorsal horn NK-1R mRNA levels and significantly

reduced formalin-induced behavioral activity. Thus, activation

of the NK-1R during nociception increases dorsal horn NK-1R

mRNA levels through activation of transcriptional or splicing

mechanisms. The stimulation of NK-1R gene expression by

activation of the NK-1R provides a homologous mechanism for

altering the sensitivity of dorsal horn cells to substance P,

potentially via the actions of second messengers, which

presumably results in the maintenance of proper sensory

information processing during long term nociception.. 0; 0; 0;

0; 0; 0; 0; 50-00-0; 63231-63-0.

314. McCarson, K. E.; Krause, J. E. The neurokinin-1 receptor antagonist

LY306,740 blocks nociception-induced increases in dorsal horn

neurokinin-1 receptor gene expression. Mol-Pharmacol. 1996

Nov; 50(5): 1189-99; ISSN: 0026-895X.

UNITED-STATES. Dilute formalin injected into the rat hindpaw

as a nociceptive stimulus increases neurokinin-1 receptor

(NK-1R) mRNA levels in the dorsal horn of the spinal cord.

Increased NK-1R mRNA levels could result from increased

mRNA stability or an increased rate of NK-1R mRNA

transcription. In this study, RNA samples prepared from the

spinal cords of rats receiving an injection of formalin into the

right hindpaw were assayed for NK-1R mRNA with the use of

solution hybridization-nuclease protection assays. The mature

and incompletely spliced NK-1R-encoding RNAs protected by

endogenous rat RNAs were characterized by the use of NK-1R

plasmid constructs containing intron sequences. NK-1R pre-

mRNA species were enriched in the nuclear fractions of spinal

cord samples, and in the steady state, total molar amounts of

NK-1R pre-mRNAs were 2-fold greater than those of mature

NK-1R mRNA. In formalin-treated animals, the temporal

pattern of peak pre-mRNA levels compared with mature mRNA

indicated that chemogenic nociception either activates

transcription of the NK-1R gene or decreases the rate of pre-

mRNA splicing. In the ipsilateral lumbar dorsal hom, NK-1R

mRNA levels were significantly increased at 2 and 6 hr after

formalin injection. Levels of the NK-1R pre-mRNA containing

both introns A and B were significantly increased 1 hr after

formalin treatment, and levels of NK-1R pre-mRNAs containing

intron A were significantly elevated at 2 hr after formalin

treatment. Pretreatment of rats with the selective NK-1R

antagonist LY306,740 was used to determine the role of NK-1R

activation in the regulation of nociception-induced NK-1R

mRNA levels. Rats were pretreated with either LY306,740 or

LY307,679 (an inactive enantiomer) before injection of

formalin into the right hindpaw. Pretreatment with LY306,740

(but not LY307,679) completely blocked the formalin-induced

increase in dorsal horn NK-1R mRNA levels and significantly

reduced formalin-induced behavioral activity. Thus, activation

of the NK-1R during nociception increases dorsal horn NK-1R

mRNA levels through activation of transcriptional or splicing

mechanisms. The stimulation of NK-1R gene expression by

activation of the NK-1R provides a homologous mechanism for

altering the sensitivity of dorsal horn cells to substance P,

potentially via the actions of second messengers, which

presumably results in the maintenance of proper sensory

information processing during long term nociception.. 0; 0; 0;

0; 0; 0; 0; 50-00-0; 63231-63-0.

315. McCrea, D. A. Supraspinal and segmental interactions. Can-J-

Physiol-Pharmacol. 1996 Apr; 74(4): 513-7; ISSN: 0008-4212.

CANADA. For the most part descending systems evoke

movements through spinal interneurons interposed in reflex

pathways. The advantage of this arrangement is that it ensures

an integration of descending commands and proprioceptive and

other exteroceptive feedback during the production of

purposeful movement. It has also become clear that spinal

reflex pathways can be reorganized during movement and that

this could profoundly modify the effects of supraspinal

commands on motor output. Recent experiments illustrate the

existence and regulation of intrinsic motoneuron membrane

currents that can dramatically change how motoneurons

respond to descending commands. To understand how

movements are controlled we must, therefore, understand both

the activity of supraspinal motor systems and the spinal

substrate upon which these commands are exerted.

316. McCrea, D. A. Supraspinal and segmental interactions. Can-J-

Physiol-Pharmacol. 1996 Apr; 74(4): 513-7; ISSN: 0008-4212.

CANADA. For the most part descending systems evoke

movements through spinal interneurons interposed in reflex

pathways. The advantage of this arrangement is that it ensures

an integration of descending commands and proprioceptive and

other exteroceptive feedback during the production of

purposeful movement. It has also become clear that spinal

reflex pathways can be reorganized during movement and that

this could profoundly modify the effects of supraspinal

commands on motor output. Recent experiments illustrate the

existence and regulation of intrinsic motoneuron membrane

currents that can dramatically change how motoneurons

respond to descending commands. To understand how

movements are controlled we must, therefore, understand both

the activity of supraspinal motor systems and the spinal

substrate upon which these commands are exerted.

317. Melsbach, G.; Wohlschlager, A.; Spiess, M.; Gunturkun, O.

Morphological asymmetries of motoneurons innervating upper

extremities: clues to the anatomical foundations of

handedness? Int-J-Neurosci. 1996 Sep; 86(3-4): 217-24; ISSN:

0020-7454.

ENGLAND. Handedness is one of the main issues in laterality

research and is known to be related to a large number of

morphological asymmetries of the central nervous system.

However, the main focus of previous studies were cerebral

structures, which ignored the spinal cord as the most distal

neural entity innervating the muscles of the extremities. We

analyzed morphometrically motoneurons from segments

innervating the arms and hands and compared them with

motoneurons of segments that innervated the upper trunk. We

found an asymmetry with larger motoneuron perikaryas on the

right side of the spinal cord in segments innervating the upper

limbs. To our knowledge this is the first time a morphological

asymmetry on single-cell-level was shown in the spinal cord

of man. The possible relation of this cellular asymmetry to the

origins of handedness is discussed.

318. Melsbach, G.; Wohlschlager, A.; Spiess, M.; Gunturkun, O.

Morphological asymmetries of motoneurons innervating upper

extremities: clues to the anatomical foundations of

handedness? Int-J-Neurosci. 1996 Sep; 86(3-4): 217-24; ISSN:

0020-7454.

ENGLAND. Handedness is one of the main issues in laterality

research and is known to be related to a large number of

morphological asymmetries of the central nervous system.

However, the main focus of previous studies were cerebral

structures, which ignored the spinal cord as the most distal

neural entity innervating the muscles of the extremities. We

analyzed morphometrically motoneurons from segments

innervating the arms and hands and compared them with

motoneurons of segments that innervated the upper trunk. We

found an asymmetry with larger motoneuron perikaryas on the

right side of the spinal cord in segments innervating the upper

limbs. To our knowledge this is the first time a morphological

asymmetry on single-cell-level was shown in the spinal cord

of man. The possible relation of this cellular asymmetry to the

origins of handedness is discussed.

319. Meuli Simmen, C.; Meuli, M.; Hutchins, G. M.; Yingling, C. D.;

Timmel, G. B.; Harrison, M. R.; Adzick, N. S. The fetal spinal cord

does not regenerate after in utero transection in a large

mammalian model. Neurosurgery. 1996 Sep; 39(3): 555-60;

discussion 560-1; ISSN: 0148-396X.

UNITED-STATES. OBJECTIVE: Regeneration and functional

recovery after spinal cord transection do not occur in

mammalian animals and humans postnatally. The goal of this

study was to test whether in utero transection of the fetal

spinal cord is succeeded by anatomic healing and functional

recovery. METHODS: In five sheep fetuses, at 60 days of

gestation and 75 days of gestation (term = 150 d), the spinal

cord was completely transected at T10. The animals were

delivered near term by cesarean section for clinical

evaluation, measurement of cortical somatosensory evoked

potentials, and morphological assessment. RESULTS: The

newborn lambs demonstrated sensory-motor paraplegia, were

incontinent of urine and stool, and exhibited a spinally

generated, ambulatory pattern of the hindlimbs. No cortical

somatosensory evoked potentials could be recorded in response

to posterior tibial nerve stimulation, although potentials from

the ulnar nerve, which enters the cord rostral to the lesion,

were normal in all animals. Histologically, no neuronal

connections across the transection site were identified. The

cord proximal to the lesion was grossly normal, whereas

distal to the transection, it appeared slightly smaller but with

the cytoarchitecture preserved. CONCLUSIONS: Unlike in lower

vertebrate and avian species, the fetal ovine spinal cord has no

detectable spontaneous regenerative capabilities when

transected during midgestation. Gap formation after

transection, secondary posttraumatic cell death, and missing

guiding channels for sprouting axons may be factors involved

in the absence of any regenerative response.

320. Meuli Simmen, C.; Meuli, M.; Hutchins, G. M.; Yingling, C. D.;

Timmel, G. B.; Harrison, M. R.; Adzick, N. S. The fetal spinal cord

does not regenerate after in utero transection in a large

mammalian model. Neurosurgery. 1996 Sep; 39(3): 555-60;

discussion 560-1; ISSN: 0148-396X.

UNITED-STATES. OBJECTIVE: Regeneration and functional

recovery after spinal cord transection do not occur in

mammalian animals and humans postnatally. The goal of this

study was to test whether in utero transection of the fetal

spinal cord is succeeded by anatomic healing and functional

recovery. METHODS: In five sheep fetuses, at 60 days of

gestation and 75 days of gestation (term = 150 d), the spinal

cord was completely transected at T10. The animals were

delivered near term by cesarean section for clinical

evaluation, measurement of cortical somatosensory evoked

potentials, and morphological assessment. RESULTS: The

newborn lambs demonstrated sensory-motor paraplegia, were

incontinent of urine and stool, and exhibited a spinally

generated, ambulatory pattern of the hindlimbs. No cortical

somatosensory evoked potentials could be recorded in response

to posterior tibial nerve stimulation, although potentials from

the ulnar nerve, which enters the cord rostral to the lesion,

were normal in all animals. Histologically, no neuronal

connections across the transection site were identified. The

cord proximal to the lesion was grossly normal, whereas

distal to the transection, it appeared slightly smaller but with

the cytoarchitecture preserved. CONCLUSIONS: Unlike in lower

vertebrate and avian species, the fetal ovine spinal cord has no

detectable spontaneous regenerative capabilities when

transected during midgestation. Gap formation after

transection, secondary posttraumatic cell death, and missing

guiding channels for sprouting axons may be factors involved

in the absence of any regenerative response.

321. Michaloudi, H. C.; Papadopoulos, G. C. Noradrenergic and

dopaminergic systems in the central nervous system of the

hedgehog (Erinaceus europaeus). J-Hirnforsch. 1996; 37(3):

319-50; ISSN: 0021-8359.

GERMANY. The distribution of the noradrenaline (NA)- and

dopamine (DA)-containing neuronal structures in the central

nervous system of the hedgehog (Erinaceus europaeus), a

phylogenetically old mammalian species, was

immunocytochemically studied employing antibodies directed

against the catecholamines (CA) themselves. Groups of DA cell

bodies observed in this study were similar to those present in

other species but the distributional map of the NA-containing

cell bodies exhibited some peculiarities. Prominent among

them were the absence of the A3 group and the paucity of CA

cells in the A2 group. DA neurons in the hypothalamus, apart

from the densely populated paraventricular and arcuate nuclei,

were fewer and less widely distributed than in other species.

In the hedgehog mesencepha- Ion, in contrast to what has been

described in other species, the major DA cell group was

present in the ventral tegmental area. CA immunoreactive

fibers were widely distributed in the CNS of the hedgehog.

However, similarly to what has been observed in other species,

terminal fields of DA neurons were much more restricted when

compared to those of the NA neurons. The neocortical DA

projection system of the hedgehog appeared less developed but

organized similar to that of the rat, and even less developed

than that of the primates. The lack of profound regional and

laminar variations in the density of cortical NA fibers in the

hedgehog enhances the suggestion that the elaboration and

differentiation of the NA cortical system parallels the

phylogenetic development of the cortex. In the brainstem,

interspecies differences in the distribution of the CA fibers

were found to concern primarily some hypothalamic areas

(medial preoptic area, suprachiasmatic nucleus, arcuate

nucleus). Such differences in the thalamus concerned the NA

innervation and they were notably present in the visual

thalamic nuclei (dorsal lateral geniculate nucleus, lateral

posterior thalamic nucleus). In the spinal cord, which was

found to receive fewer CA afferents than those found in other

species, the density of the DA fibers was much lower than that

of the NA axons. In addition to the CNS areas that have been

described in other species to receive catecholaminergic

innervation, the present study showed that both types of

catecholaminergic fibers are distributed in the choroid plexus

and along the ventricular wall of the brain ventricles and the

central canal of the hedgehog.. 51-61-6.

322. Michaloudi, H. C.; Papadopoulos, G. C. Noradrenergic and

dopaminergic systems in the central nervous system of the

hedgehog (Erinaceus europaeus). J-Hirnforsch. 1996; 37(3):

319-50; ISSN: 0021-8359.

GERMANY. The distribution of the noradrenaline (NA)- and

dopamine (DA)-containing neuronal structures in the central

nervous system of the hedgehog (Erinaceus europaeus), a

phylogenetically old mammalian species, was

immunocytochemically studied employing antibodies directed

against the catecholamines (CA) themselves. Groups of DA cell

bodies observed in this study were similar to those present in

other species but the distributional map of the NA-containing

cell bodies exhibited some peculiarities. Prominent among

them were the absence of the A3 group and the paucity of CA

cells in the A2 group. DA neurons in the hypothalamus, apart

from the densely populated paraventricular and arcuate nuclei,

were fewer and less widely distributed than in other species.

In the hedgehog mesencepha- Ion, in contrast to what has been

described in other species, the major DA cell group was

present in the ventral tegmental area. CA immunoreactive

fibers were widely distributed in the CNS of the hedgehog.

However, similarly to what has been observed in other species,

terminal fields of DA neurons were much more restricted when

compared to those of the NA neurons. The neocortical DA

projection system of the hedgehog appeared less developed but

organized similar to that of the rat, and even less developed

than that of the primates. The lack of profound regional and

laminar variations in the density of cortical NA fibers in the

hedgehog enhances the suggestion that the elaboration and

differentiation of the NA cortical system parallels the

phylogenetic development of the cortex. In the brainstem,

interspecies differences in the distribution of the CA fibers

were found to concern primarily some hypothalamic areas

(medial preoptic area, suprachiasmatic nucleus, arcuate

nucleus). Such differences in the thalamus concerned the NA

innervation and they were notably present in the visual

thalamic nuclei (dorsal lateral geniculate nucleus, lateral

posterior thalamic nucleus). In the spinal cord, which was

found to receive fewer CA afferents than those found in other

species, the density of the DA fibers was much lower than that

of the NA axons. In addition to the CNS areas that have been

described in other species to receive catecholaminergic

innervation, the present study showed that both types of

catecholaminergic fibers are distributed in the choroid plexus

and along the ventricular wall of the brain ventricles and the

central canal of the hedgehog.. 51-61-6.

323. Miehe, M.; Leterrier, J. F.; Deloulme, J. C.; Gensburger, C.;

Knoetgen, M. F.; Sensenbrenner, M. Influence of basic fibroblast

growth factor and astroglial cells on the ultrastructure of

developing rat brain neuronal precursors in vitro. Dev-

Neurosci. 1996; 18(3): 210-23; ISSN: 0378-5866.

SWITZERLAND. We have examined the ultrastructural aspect of

neuronal precursors derived from 14-day-old rat embryos

during their development under various culture conditions.

Cells maintained in serum-free medium which have developed

for 1 week in vitro present ultrastructural features of young

neurons. They contain many free ribosomes and microtubules,

but few other organelles and incompletely developed Golgi

apparatus. In the presence of basic fibroblast growth factor

(bFGF), besides cells remaining in aggregates and displaying

morphological features of undifferentiated cells, dispersed

neuroblasts underwent accelerated ultrastructural maturation.

They present well-developed Golgi apparatus, axodendritic

synapses and dense-core vesicles already after 3 days in

culture. By contrast, in the presence of astroglial-conditioned

medium a more homogeneous population developed showing

ultrastructural features of relatively mature neurons.

However, the neuronal precursors acquired the most mature

ultrastructural aspect when they were cocultured with

astroglial cells. The neuronal cell bodies contain highly

developed Golgi complexes, well-differentiated ergastoplasm

and Niss1 body formations, while in the complex neurite

network much more numerous mature synapses with clear and

dense-core vesicles are visible. These observations indicate

that a combination of soluble factors and membrane-bound

factors is essential for extensive ultrastructural development

of neuronal precursors in vitro. Another finding was that in

these cultured neurons neurofilaments (NF) were never seen,

while NF protein subunits were found. These data suggest that

the polymerization of the three NF subunits into intermediate

filaments might need particular cellular factors which

probably do not exist under our in vitro conditions.. 0; 0; 0.

324. Miehe, M.; Leterrier, J. F.; Deloulme, J. C.; Gensburger, C.;

Knoetgen, M. F.; Sensenbrenner, M. Influence of basic fibroblast

growth factor and astroglial cells on the ultrastructure of

developing rat brain neuronal precursors in vitro. Dev-

Neurosci. 1996; 18(3): 210-23; ISSN: 0378-5866.

SWITZERLAND. We have examined the ultrastructural aspect of

neuronal precursors derived from 14-day-old rat embryos

during their development under various culture conditions.

Cells maintained in serum-free medium which have developed

for 1 week in vitro present ultrastructural features of young

neurons. They contain many free ribosomes and microtubules,

but few other organelles and incompletely developed Golgi

apparatus. In the presence of basic fibroblast growth factor

(bFGF), besides cells remaining in aggregates and displaying

morphological features of undifferentiated cells, dispersed

neuroblasts underwent accelerated ultrastructural maturation.

They present well-developed Golgi apparatus, axodendritic

synapses and dense-core vesicles already after 3 days in

culture. By contrast, in the presence of astroglial-conditioned

medium a more homogeneous population developed showing

ultrastructural features of relatively mature neurons.

However, the neuronal precursors acquired the most mature

ultrastructural aspect when they were cocultured with

astroglial cells. The neuronal cell bodies contain highly

developed Golgi complexes, well-differentiated ergastoplasm

and Niss1 body formations, while in the complex neurite

network much more numerous mature synapses with clear and

dense-core vesicles are visible. These observations indicate

that a combination of soluble factors and membrane-bound

factors is essential for extensive ultrastructural development

of neuronal precursors in vitro. Another finding was that in

these cultured neurons neurofilaments (NF) were never seen,

while NF protein subunits were found. These data suggest that

the polymerization of the three NF subunits into intermediate

filaments might need particular cellular factors which

probably do not exist under our in vitro conditions.. 0; 0; 0.

325. Miller, B. A.; Woolf, C. J. Glutamate-mediated slow synaptic

currents in neonatal rat deep dorsal horn neurons in vitro. J-

Neurophysiol. 1996 Sep; 76(3): 1465-76; ISSN: 0022-3077.

UNITED-STATES. 1. The role of glutamate in slow excitatory

synaptic transmission between small-diameter primary

afferents and deep dorsal horn neurons was examined in

neonatal rat spinal cord in vitro with the use of the whole cell

voltage-clamp technique. 2. Single-shock electrical

stimulation of large-diameter A beta-fibers evoked a short-

latency (< 10 ms) fast (< 500 ms) excitatory postsynaptic

current (EPSC). Stimulation of small-diameter A delta- and C

fibers resulted, in addition, in a slowly rising and decaying

EPSC (lasting up to 14 s) following the fast EPSC. The slow

EPSC was never observed with stimulation of A beta-fibers. 3.

Two patterns of EPSCs were observed, "type 1" and "type 2,"

which differed in their time course (lasting up to 1 and 14 s,

respectively). The type 1 response was biphasic, with a fast

monosynaptic component followed by an invariant, presumably

monosynaptic, late slow component. The type 2 response was

multiphasic, with a fast monosynaptic component followed by

a slow component composed of fast polysynaptic currents

superimposed on a slow current. 4. The fast monosynaptic

component had a linear conductance, whereas the late slower

component of the A beta-fiber-evoked response had a negative

slope conductance at holding potentials more negative than -

23 mV. Both currents reversed at a membrane potential of -1.2

+/- 2.8 (SE) mV. 5. With the use of selective non-N-methyl-D-

aspartate (non-NMDA) and NMDA receptor antagonists [6-

cyano-7-nitroquinox-aline-2,3-dione (CNQX) or 2,3-dihydroxy-

6-nitro-7-sulphamoyl-benzo (F) quinoxaline and D(-)-2-

amino-5-phosphonopentanoic acid (D-AP5), respectively] we

showed that both the early fast (A beta-fiber evoked) and the

late slow (A delta- and C fiber evoked) components were

mediated by non-NMDA and NMDA receptors. CNQX suppressed

both the early fast and late slow components of the compound

EPSC, whereas D-AP5 suppressed the polysynaptic currents of

the early fast component and the late slow component without

significantly affecting the early fast monosynaptic component.

6. Slow EPSCs summated on low-frequency (1 or 10 Hz),

repetitive stimulation and produced long-duration "tail"

currents on cessation of the stimulus. The amount of temporal

summation was proportional to the duration of the slow EPSC

and the frequency of stimulation. 7. Our results suggest that

slow ionotropic-glutamate-receptor-mediated EPSCs produced

by the stimulation of small-diameter primary afferents play

an important role in activity-dependent synaptic plasticity in

the dorsal horn.. 0; 0; 0; 0; 56-86-0; 7440-46-2.

326. Miller, B. A.; Woolf, C. J. Glutamate-mediated slow synaptic

currents in neonatal rat deep dorsal horn neurons in vitro. J-

Neurophysiol. 1996 Sep; 76(3): 1465-76; ISSN: 0022-3077.

UNITED-STATES. 1. The role of glutamate in slow excitatory

synaptic transmission between small-diameter primary

afferents and deep dorsal horn neurons was examined in

neonatal rat spinal cord in vitro with the use of the whole cell

voltage-clamp technique. 2. Single-shock electrical

stimulation of large-diameter A beta-fibers evoked a short-

latency (< 10 ms) fast (< 500 ms) excitatory postsynaptic

current (EPSC). Stimulation of small-diameter A delta- and C

fibers resulted, in addition, in a slowly rising and decaying

EPSC (lasting up to 14 s) following the fast EPSC. The slow

EPSC was never observed with stimulation of A beta-fibers. 3.

Two patterns of EPSCs were observed, "type 1" and "type 2,"

which differed in their time course (lasting up to 1 and 14 s,

respectively). The type 1 response was biphasic, with a fast

monosynaptic component followed by an invariant, presumably

monosynaptic, late slow component. The type 2 response was

multiphasic, with a fast monosynaptic component followed by

a slow component composed of fast polysynaptic currents

superimposed on a slow current. 4. The fast monosynaptic

component had a linear conductance, whereas the late slower

component of the A beta-fiber-evoked response had a negative

slope conductance at holding potentials more negative than -

23 mV. Both currents reversed at a membrane potential of -1.2

+/- 2.8 (SE) mV. 5. With the use of selective non-N-methyl-D-

aspartate (non-NMDA) and NMDA receptor antagonists [6-

cyano-7-nitroquinox-aline-2,3-dione (CNQX) or 2,3-dihydroxy-

6-nitro-7-sulphamoyl-benzo (F) quinoxaline and D(-)-2-

amino-5-phosphonopentanoic acid (D-AP5), respectively] we

showed that both the early fast (A beta-fiber evoked) and the

late slow (A delta- and C fiber evoked) components were

mediated by non-NMDA and NMDA receptors. CNQX suppressed

both the early fast and late slow components of the compound

EPSC, whereas D-AP5 suppressed the polysynaptic currents of

the early fast component and the late slow component without

significantly affecting the early fast monosynaptic component.

6. Slow EPSCs summated on low-frequency (1 or 10 Hz),

repetitive stimulation and produced long-duration "tail"

currents on cessation of the stimulus. The amount of temporal

summation was proportional to the duration of the slow EPSC

and the frequency of stimulation. 7. Our results suggest that

slow ionotropic-glutamate-receptor-mediated EPSCs produced

by the stimulation of small-diameter primary afferents play

an important role in activity-dependent synaptic plasticity in

the dorsal horn.. 0; 0; 0; 0; 56-86-0; 7440-46-2.

327. Momiyama, A.; Feldmeyer, D.; Cull Candy, S. G. Identification of a

native low-conductance NMDA channel with reduced

sensitivity to Mg2+ in rat central neurones. J-Physiol-Lond.

1996 Jul 15; 494( Pt 2): 479-92; ISSN: 0022-3751.

ENGLAND. 1. We have identified a new type of NMDA channel in

rat central neurones that express mRNA for the NR2D subunit.

We have examined single NMDA channels in cerebellar Purkinje

cells (which possess NR1 and 2D), deep cerebellar nuclei (NR1,

2A, 2B and 2D) and spinal cord dorsal horn neurones (NR1, 2B

and 2D). 2. In Purkinje cells, NMDA opened channels with a

main conductance of 37.9 +/- 1.1 pS and a subconductance of

17.8 +/- 0.7 pS, with frequent transitions between the two

levels. 3. NMDA activated low-conductance ('38/18 pS') events

(along with high-conductance--'50/40 pS'--openings) in some

patches from deep cerebellar nuclei and dorsal horn neurones.

Our evidence suggests that 38/18 pS and 50/40 pS events

arose from distinct types of NMDA receptors. 4. The

transitions for 38/18 pS events were asymmetrical: steps

from 38 to 18 pS were more frequent (72.2%) than steps from

18 to 38 pS. This feature appeared common to the 38/18 pS

events in all three cell types, suggesting similarity in the

low-conductance channels. 5. The 38/18 pS channels in

Purkinje cells exhibited characteristic NMDA receptor

properties, including requirement for glycine, antagonism by

D-2-amino-5-phosphonopentanoic acid (D-AP5) and 7-

chlorokynurenic acid, and voltage-dependent block by

extracellular Mg2+. 6. The mean open time for the 38 pS state

(0.74 +/- 0.07 ms) was significantly briefer than that for the

18 pS state (1.27 +/- 0.18 ms). 7. Mg2+ block of low-

conductance NMDA channels in Purkinje cells was less marked

than block of 50/40 pS channels in cerebellar granule cells. 8.

The time course of appearance of 38/18 pS NMDA channels

matched the expression of mRNA for the NR2D subunit. Thus

38/18 pS events were present in > 70% of Purkinje cell

patches in 0- to 8-day-old animals, and absent by postnatal

day 12. 9. We propose that the 38/18 pS NMDA channels

identified here (associated with the NR2D subunit), and the

other low-conductance NMDA channel associated with the

NR2C subunit, may together constitute a functionally distinct

subclass of native NMDA receptors.. 0; 0; 0; 18000-24-3; 492-

27-3; 7439-95-4; 76726-92-6.

328. Momiyama, A.; Feldmeyer, D.; Cull Candy, S. G. Identification of a

native low-conductance NMDA channel with reduced

sensitivity to Mg2+ in rat central neurones. J-Physiol-Lond.

1996 Jul 15; 494( Pt 2): 479-92; ISSN: 0022-3751.

ENGLAND. 1. We have identified a new type of NMDA channel in

rat central neurones that express mRNA for the NR2D subunit.

We have examined single NMDA channels in cerebellar Purkinje

cells (which possess NR1 and 2D), deep cerebellar nuclei (NR1,

2A, 2B and 2D) and spinal cord dorsal horn neurones (NR1, 2B

and 2D). 2. In Purkinje cells, NMDA opened channels with a

main conductance of 37.9 +/- 1.1 pS and a subconductance of

17.8 +/- 0.7 pS, with frequent transitions between the two

levels. 3. NMDA activated low-conductance ('38/18 pS') events

(along with high-conductance--'50/40 pS'--openings) in some

patches from deep cerebellar nuclei and dorsal horn neurones.

Our evidence suggests that 38/18 pS and 50/40 pS events

arose from distinct types of NMDA receptors. 4. The

transitions for 38/18 pS events were asymmetrical: steps

from 38 to 18 pS were more frequent (72.2%) than steps from

18 to 38 pS. This feature appeared common to the 38/18 pS

events in all three cell types, suggesting similarity in the

low-conductance channels. 5. The 38/18 pS channels in

Purkinje cells exhibited characteristic NMDA receptor

properties, including requirement for glycine, antagonism by

D-2-amino-5-phosphonopentanoic acid (D-AP5) and 7-

chlorokynurenic acid, and voltage-dependent block by

extracellular Mg2+. 6. The mean open time for the 38 pS state

(0.74 +/- 0.07 ms) was significantly briefer than that for the

18 pS state (1.27 +/- 0.18 ms). 7. Mg2+ block of low-

conductance NMDA channels in Purkinje cells was less marked

than block of 50/40 pS channels in cerebellar granule cells. 8.

The time course of appearance of 38/18 pS NMDA channels

matched the expression of mRNA for the NR2D subunit. Thus

38/18 pS events were present in > 70% of Purkinje cell

patches in 0- to 8-day-old animals, and absent by postnatal

day 12. 9. We propose that the 38/18 pS NMDA channels

identified here (associated with the NR2D subunit), and the

other low-conductance NMDA channel associated with the

NR2C subunit, may together constitute a functionally distinct

subclass of native NMDA receptors.. 0; 0; 0; 18000-24-3; 492-

27-3; 7439-95-4; 76726-92-6.

329. Motorina, M. V. [The ultrastructural characteristics of the

sensorimotor synapses in the amphibian spinal cord].

Ul'trastrukturnye osobennosti sensomotornykh sinapsov v

spinnom mozge amfibii. Morfologiia. 1996; 110(4): 48-55;

ISSN: 0004-1947.

RUSSIA. The present electron microscopic study aims to

analyse sensomotor synapses ultrastructural peculiarities in

part deafferentation and neuroplasmic transport to horse-

radish peroxidase through the sectioned dorsal radix. Three

zones of primary afferent fibres endings, including motor

nuclear zone were found in the amphibian spinal cord. The data

obtained demonstrated the probability of both chemical and

combined (electrochemical, mostly of axodendritic type) origin

of synapses, formed by primary afferent fibres on motor

neurons somato-dendritic membrane. Complex synapses are

likely to acquire peculiar importance in deafferentation. These

data correlate with microphysiological research on amphibians

sensomotor synaptic contacts.. EC 1.11.1.-.

330. Motorina, M. V. [The ultrastructural characteristics of the

sensorimotor synapses in the amphibian spinal cord].

Ul'trastrukturnye osobennosti sensomotornykh sinapsov v

spinnom mozge amfibii. Morfologiia. 1996; 110(4): 48-55;

ISSN: 0004-1947.

RUSSIA. The present electron microscopic study aims to

analyse sensomotor synapses ultrastructural peculiarities in

part deafferentation and neuroplasmic transport to horse-

radish peroxidase through the sectioned dorsal radix. Three

zones of primary afferent fibres endings, including motor

nuclear zone were found in the amphibian spinal cord. The data

obtained demonstrated the probability of both chemical and

combined (electrochemical, mostly of axodendritic type) origin

of synapses, formed by primary afferent fibres on motor

neurons somato-dendritic membrane. Complex synapses are

likely to acquire peculiar importance in deafferentation. These

data correlate with microphysiological research on amphibians

sensomotor synaptic contacts.. EC 1.11.1.-.

331. Myers, M. R. A numerical investigation into factors affecting

anesthetic distribution during spinal anesthesia. J-Biomech.

1996 Feb; 29(2): 139-49; ISSN: 0021-9290.

UNITED-STATES. The factors affecting distribution of

anesthetic within the spinal column are of current interest

due to recent reports of neurological injury occurring during

spinal anesthesia. This paper describes a numerical model for

simulating anesthetic dispersion, and applies the model to the

evaluation of spinal-column size, anesthetic injection rate,

and catheter orientation as factors influencing the anesthetic

distribution. The model is based upon the finite-element

method and incorporates a three-dimensional geometry derived

from images of human spinal columns. Simulation results show

that the ratio of the cross-sectional dimension of the

subarachnoid space within the spinal column to the diameter

of the catheter is a critical parameter, with low values of this

ratio producing the most uniform anesthetic distributions.

Increasing injection rate is found to produce a less uniform

distribution in a global sense (higher total volume of

anesthetic in the 'sacral' half) but a more uniform distribution

in a localized sense (lower concentrations at critical points).

Finally, the anesthetic distribution is demonstrated to be

highly sensitive to orientation angle at high injection rates..

0.

332. Myers, M. R. A numerical investigation into factors affecting

anesthetic distribution during spinal anesthesia. J-Biomech.

1996 Feb; 29(2): 139-49; ISSN: 0021-9290.

UNITED-STATES. The factors affecting distribution of

anesthetic within the spinal column are of current interest

due to recent reports of neurological injury occurring during

spinal anesthesia. This paper describes a numerical model for

simulating anesthetic dispersion, and applies the model to the

evaluation of spinal-column size, anesthetic injection rate,

and catheter orientation as factors influencing the anesthetic

distribution. The model is based upon the finite-element

method and incorporates a three-dimensional geometry derived

from images of human spinal columns. Simulation results show

that the ratio of the cross-sectional dimension of the

subarachnoid space within the spinal column to the diameter

of the catheter is a critical parameter, with low values of this

ratio producing the most uniform anesthetic distributions.

Increasing injection rate is found to produce a less uniform

distribution in a global sense (higher total volume of

anesthetic in the 'sacral' half) but a more uniform distribution

in a localized sense (lower concentrations at critical points).

Finally, the anesthetic distribution is demonstrated to be

highly sensitive to orientation angle at high injection rates..

0.

333. Nadon, N. L.; Duncan, I. D. Molecular analysis of glial cell

development in the canine 'shaking pup' mutant. Dev-Neurosci.

1996; 18(3): 174-84; ISSN: 0378-5866.

SWITZERLAND. The shaking pup, a canine mutant, carries a

point mutation in the myelin proteolipid protein (PLP) gene

that causes dysmyelination of the central nervous system

(CNS) with resultant tremor, seizures, and other persistent

neurological deficits. The developmental potential of glial

cells in the shaking pup CNS and peripheral nervous system

(PNS) was evaluated by quantitative analysis of the expression

of several glial-specific genes. All of the myelin-associated

genes demonstrated developmental patterns of expression

similar to those observed in the controls, but at significantly

reduced levels. Expression of the genes for the major CNS

myelin proteins, PLP and the myelin basic protein, are most

dramatically affected in the shaking pup, although reduced

expression levels are observed for other oligodendrocyte-

specific genes such as 2',3'-cyclic nucleotide

3'phosphodiesterase and glucose phosphate dehydrogenase. The

pattern of gene expression in the shaking pup indicates that

the oligodendrocytes experience an inhibition in development

after the myelination program has begun. There appears to be

little evidence for an astrocytic response to the

dysmyelinating condition at the RNA level, but we present

evidence for ectopic expression of P0 mRNA in the CNS.

Expression of the P0 and PLP genes in the sciatic nerve

appears to be normal, reinforcing previous reports that PNS

myelination is unaffected by the mutation in the PLP gene.. 0;

0; 0; 0.

334. Nadon, N. L.; Duncan, I. D. Molecular analysis of glial cell

development in the canine 'shaking pup' mutant. Dev-Neurosci.

1996; 18(3): 174-84; ISSN: 0378-5866.

SWITZERLAND. The shaking pup, a canine mutant, carries a

point mutation in the myelin proteolipid protein (PLP) gene

that causes dysmyelination of the central nervous system

(CNS) with resultant tremor, seizures, and other persistent

neurological deficits. The developmental potential of glial

cells in the shaking pup CNS and peripheral nervous system

(PNS) was evaluated by quantitative analysis of the expression

of several glial-specific genes. All of the myelin-associated

genes demonstrated developmental patterns of expression

similar to those observed in the controls, but at significantly

reduced levels. Expression of the genes for the major CNS

myelin proteins, PLP and the myelin basic protein, are most

dramatically affected in the shaking pup, although reduced

expression levels are observed for other oligodendrocyte-

specific genes such as 2',3'-cyclic nucleotide

3'phosphodiesterase and glucose phosphate dehydrogenase. The

pattern of gene expression in the shaking pup indicates that

the oligodendrocytes experience an inhibition in development

after the myelination program has begun. There appears to be

little evidence for an astrocytic response to the

dysmyelinating condition at the RNA level, but we present

evidence for ectopic expression of P0 mRNA in the CNS.

Expression of the P0 and PLP genes in the sciatic nerve

appears to be normal, reinforcing previous reports that PNS

myelination is unaffected by the mutation in the PLP gene.. 0;

0; 0; 0.

335. Nagy, I.; Woolf, C. J. Lignocaine selectively reduces C fibre-

evoked neuronal activity in rat spinal cord in vitro by

decreasing N-methyl-D-aspartate and neurokinin receptor-

mediated post-synaptic depolarizations; implications for the

development of novel centrally acting analgesics. Pain. 1996

Jan; 64(1): 59-70; ISSN: 0304-3959.

NETHERLANDS. The action of lignocaine on nociceptive

transmission in the spinal cord has been studied in vitro using

ventral root potential (VRP) recordings from 10-12-day-old

rat hemisected spinal cord preparations. Single-shock

stimulation of a dorsal root at intensities sufficient to

activate high-threshold C-primary afferent fibres elicited

VRPs lasting for 15-20 sec in the corresponding ventral root.

The VRP consisted of 3 distinct parts: the early, slow and

prolonged components, as previously described (Thompson et

al. 1992), where the early represents A beta fibre-evoked

mono- and polysynaptic responses lasting for tens of

milliseconds, the slow is a largely N-methyl-D-aspartic acid

(NMDA) receptor-mediated small-calibre afferent-generated

component, lasting for about 1.5 sec, and the prolonged is a

neurokinin receptor-mediated long-lasting component

generated by high-threshold fibres. Lignocaine superfusion

(40-60 microM) significantly and reversibly reduced the slow

and prolonged components of the C fibre-evoked VRP in a dose-

dependent manner without any effect on the early or A beta

fibre-mediated component of the VRP. The amplitude of the

cumulative VRP generated by repetitive inputs (1 and 10 Hz)

was also significantly reduced as was the depolarization

produced by bath application of NMDA (100 microM) or

substance P (SP, 1 microM) in the presence or absence of

tetrodotoxin (TTX) (300 nM). At this dose range lignocaine had

no effect on the compound action potential (CAP) elicited by

stimulating the sciatic nerve and recorded on the dorsal root.

The CAP was only significantly reduced with a 300 microM

dose of lignocaine. Application of the opiate, glycine, GABAA

and GABAB receptor antagonists, naloxone (1 microM),

strychnine (100 microM), bicuculline (100 microM) and

phaclofen (100 microM) did not alter the depressant effects of

lignocaine on the VRP. Low concentrations of lignocaine have a

selective action on nociceptive transmission in the spinal cord

which is different and more potent than its local anaesthetic

conduction blockade in the periphery. This includes a reduction

of direct or synaptically driven NMDA- and NK receptor-

mediated post-synaptic depolarizations indicating that this

class of sodium channel blockers may be potentially useful as

analgesic agents, possibly acting on TTX-resistant sodium ion

channels.. 0; 0; 137-58-6.

336. Nagy, I.; Woolf, C. J. Lignocaine selectively reduces C fibre-

evoked neuronal activity in rat spinal cord in vitro by

decreasing N-methyl-D-aspartate and neurokinin receptor-

mediated post-synaptic depolarizations; implications for the

development of novel centrally acting analgesics. Pain. 1996

Jan; 64(1): 59-70; ISSN: 0304-3959.

NETHERLANDS. The action of lignocaine on nociceptive

transmission in the spinal cord has been studied in vitro using

ventral root potential (VRP) recordings from 10-12-day-old

rat hemisected spinal cord preparations. Single-shock

stimulation of a dorsal root at intensities sufficient to

activate high-threshold C-primary afferent fibres elicited

VRPs lasting for 15-20 sec in the corresponding ventral root.

The VRP consisted of 3 distinct parts: the early, slow and

prolonged components, as previously described (Thompson et

al. 1992), where the early represents A beta fibre-evoked

mono- and polysynaptic responses lasting for tens of

milliseconds, the slow is a largely N-methyl-D-aspartic acid

(NMDA) receptor-mediated small-calibre afferent-generated

component, lasting for about 1.5 sec, and the prolonged is a

neurokinin receptor-mediated long-lasting component

generated by high-threshold fibres. Lignocaine superfusion

(40-60 microM) significantly and reversibly reduced the slow

and prolonged components of the C fibre-evoked VRP in a dose-

dependent manner without any effect on the early or A beta

fibre-mediated component of the VRP. The amplitude of the

cumulative VRP generated by repetitive inputs (1 and 10 Hz)

was also significantly reduced as was the depolarization

produced by bath application of NMDA (100 microM) or

substance P (SP, 1 microM) in the presence or absence of

tetrodotoxin (TTX) (300 nM). At this dose range lignocaine had

no effect on the compound action potential (CAP) elicited by

stimulating the sciatic nerve and recorded on the dorsal root.

The CAP was only significantly reduced with a 300 microM

dose of lignocaine. Application of the opiate, glycine, GABAA

and GABAB receptor antagonists, naloxone (1 microM),

strychnine (100 microM), bicuculline (100 microM) and

phaclofen (100 microM) did not alter the depressant effects of

lignocaine on the VRP. Low concentrations of lignocaine have a

selective action on nociceptive transmission in the spinal cord

which is different and more potent than its local anaesthetic

conduction blockade in the periphery. This includes a reduction

of direct or synaptically driven NMDA- and NK receptor-

mediated post-synaptic depolarizations indicating that this

class of sodium channel blockers may be potentially useful as

analgesic agents, possibly acting on TTX-resistant sodium ion

channels.. 0; 0; 137-58-6.

337. Nerobkova, L. N.; Markina, N. V.; Voronina, T. A.; Kraineva, V. A.;

Garibova, T. L.; Molodavkin, G. M.; Sharkova, L. M. [Sleep

disorders and impaired learning ability in rats with

parkinsonian syndrome induced by MPTP]. Narushenie struktury

sna i sposobnosti k obucheniiu u krys s parkinsonicheskim

sindromom, vyzvannym MFTP. Biull-Eksp-Biol-Med. 1996 Sep;

122(9): 288-91; ISSN: 0365-9615.

RUSSIA. 0; 28289-54-5.

338. Nerobkova, L. N.; Markina, N. V.; Voronina, T. A.; Kraineva, V. A.;

Garibova, T. L.; Molodavkin, G. M.; Sharkova, L. M. [Sleep

disorders and impaired learning ability in rats with

parkinsonian syndrome induced by MPTP]. Narushenie struktury

sna i sposobnosti k obucheniiu u krys s parkinsonicheskim

sindromom, vyzvannym MFTP. Biull-Eksp-Biol-Med. 1996 Sep;

122(9): 288-91; ISSN: 0365-9615.

RUSSIA. 0; 28289-54-5.

339. Nicolas, S.; Massacrier, A.; Caubit, X.; Cau, P.; Le Parco, Y. A

Distal-less-like gene is induced in the regenerating central

nervous system of the urodele Pleurodeles waltl. Mech-Dev.

1996 May; 56(1-2): 209-20; ISSN: 0925-4773.

IRELAND. We report the cloning of a Distal-less-like gene

(PwDlx-3) and its pattern of expression during embryonic

development and adult tail regeneration in the urodele

Pleurodeles waltl. Using RT-PCR and in situ hybridization

experiments we determined that, during regeneration, PwDlx-3

is expressed in the epidermis, the cells associated with

muscle masses and in the ventrolateral parts of the ependymal

tube. PwDlx-3 localization in the muscle masses and in cells

of the ependymal tube, which give rise during regeneration to

the ventral roots and the spinal ganglia, suggests that this

gene might be expressed in cells which have some neural crest

cell potentialities. PwDlx-3 is the first homeobox gene shown

to be expressed in the regenerating spinal cord but not in the

adult one and could thus be involved in the regeneration of the

nervous system.. 0; 0.

340. Nicolas, S.; Massacrier, A.; Caubit, X.; Cau, P.; Le Parco, Y. A

Distal-less-like gene is induced in the regenerating central

nervous system of the urodele Pleurodeles waltl. Mech-Dev.

1996 May; 56(1-2): 209-20; ISSN: 0925-4773.

IRELAND. We report the cloning of a Distal-less-like gene

(PwDlx-3) and its pattern of expression during embryonic

development and adult tail regeneration in the urodele

Pleurodeles waltl. Using RT-PCR and in situ hybridization

experiments we determined that, during regeneration, PwDlx-3

is expressed in the epidermis, the cells associated with

muscle masses and in the ventrolateral parts of the ependymal

tube. PwDlx-3 localization in the muscle masses and in cells

of the ependymal tube, which give rise during regeneration to

the ventral roots and the spinal ganglia, suggests that this

gene might be expressed in cells which have some neural crest

cell potentialities. PwDlx-3 is the first homeobox gene shown

to be expressed in the regenerating spinal cord but not in the

adult one and could thus be involved in the regeneration of the

nervous system.. 0; 0.

341. Nogradi, A.; Vrbova, G. Improved motor function of denervated rat

hindlimb muscles induced by embryonic spinal cord grafts.

Eur-J-Neurosci. 1996 Oct; 8(10): 2198-203; ISSN: 0953-816X.

ENGLAND. Loss of motoneurons results in a decrease in force

production by skeletal muscles and paralysis. Although it has

been shown that missing motoneurons of rats can be replaced

by embryonic homotopic neurons, attempts to guide their axons

to their target muscles that have lost their innervation have

been unsuccessful. In this study attempts were made to guide

axons from grafted embryonic motoneurons to their target via

a reimplanted ventral root. Adult hosts that received an

embryonic graft prelabelled with 5-bromo-2'-deoxyuridine had

their L4 ventral root avulsed and reimplanted into the spinal

cord. Three to six months later, neurons that had their axons in

the L4 ventral ramus were retrogradely labelled with fast blue

and diamidino yellow. In five animals that had received an

embryonic graft 116 +/- 16 cells were retrogradely labelled,

and of these at least 15% were of graft origin, since they were

positive for 5-bromo-2'-deoxyuridine. In five animals that had

their L4 ventral root reimplanted but did not receive a graft,

only 12 +/- 1.3 cells were retrogradely labelled. However,

meaningful functional recovery could be achieved only if the

regenerating axons of embryonic motoneurons found in the L4

ventral ramus were able to reverse the loss of force of

muscles that had lost their innervation. This study shows that

axons of embryonic motoneurons grafted into an adult rat

spinal cord, as well as some axons of host origin, can be

guided to denervated hindlimb muscles via reimplanted lumbar

ventral roots. In normal rats approximately 30 motor axons

innervated the extensor digitorum longus and 60 innervated

the tibialis anterior via the L4 ventral root. In rats that did

not receive a graft only 3.7 +/- 1.2 axons reached the extensor

digitorum longus and 3.5 +/- 0.4 reached the tibialis anterior

muscle via the implanted L4 ventral root. In animals that had

an embryonic graft, 7.6 +/- 0.5 axons innervated the extensor

digitorum longus and 8.5 +/- 0.5 reached the tibialis anterior

muscle via the implanted root. In rats without a transplant the

maximum tetanic tension elicited by stimulating the

implanted L4 root was 16 +/- 7 g for the extensor digitorum

longus and 53 +/- 36 g for the tibialis anterior muscle,

whereas the corresponding muscles in animals that had an

embryonic graft developed 82 +/- 16 and 281 +/- 95 g

respectively. Thus it appears that the grafted motoneurons

contributed to the innervation and functional recovery of the

denervated muscles.

342. Nogradi, A.; Vrbova, G. Improved motor function of denervated rat

hindlimb muscles induced by embryonic spinal cord grafts.

Eur-J-Neurosci. 1996 Oct; 8(10): 2198-203; ISSN: 0953-816X.

ENGLAND. Loss of motoneurons results in a decrease in force

production by skeletal muscles and paralysis. Although it has

been shown that missing motoneurons of rats can be replaced

by embryonic homotopic neurons, attempts to guide their axons

to their target muscles that have lost their innervation have

been unsuccessful. In this study attempts were made to guide

axons from grafted embryonic motoneurons to their target via

a reimplanted ventral root. Adult hosts that received an

embryonic graft prelabelled with 5-bromo-2'-deoxyuridine had

their L4 ventral root avulsed and reimplanted into the spinal

cord. Three to six months later, neurons that had their axons in

the L4 ventral ramus were retrogradely labelled with fast blue

and diamidino yellow. In five animals that had received an

embryonic graft 116 +/- 16 cells were retrogradely labelled,

and of these at least 15% were of graft origin, since they were

positive for 5-bromo-2'-deoxyuridine. In five animals that had

their L4 ventral root reimplanted but did not receive a graft,

only 12 +/- 1.3 cells were retrogradely labelled. However,

meaningful functional recovery could be achieved only if the

regenerating axons of embryonic motoneurons found in the L4

ventral ramus were able to reverse the loss of force of

muscles that had lost their innervation. This study shows that

axons of embryonic motoneurons grafted into an adult rat

spinal cord, as well as some axons of host origin, can be

guided to denervated hindlimb muscles via reimplanted lumbar

ventral roots. In normal rats approximately 30 motor axons

innervated the extensor digitorum longus and 60 innervated

the tibialis anterior via the L4 ventral root. In rats that did

not receive a graft only 3.7 +/- 1.2 axons reached the extensor

digitorum longus and 3.5 +/- 0.4 reached the tibialis anterior

muscle via the implanted L4 ventral root. In animals that had

an embryonic graft, 7.6 +/- 0.5 axons innervated the extensor

digitorum longus and 8.5 +/- 0.5 reached the tibialis anterior

muscle via the implanted root. In rats without a transplant the

maximum tetanic tension elicited by stimulating the

implanted L4 root was 16 +/- 7 g for the extensor digitorum

longus and 53 +/- 36 g for the tibialis anterior muscle,

whereas the corresponding muscles in animals that had an

embryonic graft developed 82 +/- 16 and 281 +/- 95 g

respectively. Thus it appears that the grafted motoneurons

contributed to the innervation and functional recovery of the

denervated muscles.

343. Ohta, K.; Nakamura, M.; Hirokawa, K.; Tanaka, S.; Iwama, A.; Suda,

T.; Ando, M.; Tanaka, H. The receptor tyrosine kinase, Cek8, is

transiently expressed on subtypes of motoneurons in the spinal

cord during development. Mech-Dev. 1996 Jan; 54(1): 59-69;

ISSN: 0925-4773.

IRELAND. Receptor tyrosine kinases (RTKs) play important

roles in cellular proliferation, differentiation, and survival.

We performed reverse transcriptase-polymerase chain

reactions (RT-PCR) from enriched embryonic day 5 (E5) chick

motoneurons by panning to identify RTKs involved in the early

development of motoneuron. In situ hybridization revealed that

Cek8, a member of the eph family, was specifically expressed

on motoneurons at the brachial and lumbar segments of the

spinal cord which innervate limb muscles, and disappeared

after the naturally occurring cell death period (E6-E11).

Immunohistochemistry using an anti-Cek8 monoclonal antibody

showed the localization of Cek8 protein at the cell bodies and

axonal fibers of motoneurons and muscles. The unique

expression of Cek8 suggests its involvement in cellular

survival or cell-cell interactions for specific subpopulations

of developing motoneurons.. EC 2.7.1.-; EC 2.7.1.-; 0; 0; 0; 0.

344. Ohta, K.; Nakamura, M.; Hirokawa, K.; Tanaka, S.; Iwama, A.; Suda,

T.; Ando, M.; Tanaka, H. The receptor tyrosine kinase, Cek8, is

transiently expressed on subtypes of motoneurons in the spinal

cord during development. Mech-Dev. 1996 Jan; 54(1): 59-69;

ISSN: 0925-4773.

IRELAND. Receptor tyrosine kinases (RTKs) play important

roles in cellular proliferation, differentiation, and survival.

We performed reverse transcriptase-polymerase chain

reactions (RT-PCR) from enriched embryonic day 5 (E5) chick

motoneurons by panning to identify RTKs involved in the early

development of motoneuron. In situ hybridization revealed that

Cek8, a member of the eph family, was specifically expressed

on motoneurons at the brachial and lumbar segments of the

spinal cord which innervate limb muscles, and disappeared

after the naturally occurring cell death period (E6-E11).

Immunohistochemistry using an anti-Cek8 monoclonal antibody

showed the localization of Cek8 protein at the cell bodies and

axonal fibers of motoneurons and muscles. The unique

expression of Cek8 suggests its involvement in cellular

survival or cell-cell interactions for specific subpopulations

of developing motoneurons.. EC 2.7.1.-; EC 2.7.1.-; 0; 0; 0; 0.

345. Olivier, E.; Edgley, S. A.; Armand, J.; Lemon, R. N. An

electrophysiological study of the postnatal development of the

corticospinal system in the macaque monkey. J-Neurosci. 1997

Jan 1; 17(1): 267-76; ISSN: 0270-6474.

UNITED-STATES. Postnatal development of the corticospinal

system was investigated in 13 macaques using noninvasive

transcranial magnetic stimulation (TMS) of the motor cortex

and direct electrical stimulation of corticospinal axons in the

medullary pyramid and spinal cord. The latency of antidromic

corticospinal volleys evoked from the pyramid and recorded

from the motor cortex decreased dramatically during the first

postnatal months. Our data predict that conduction velocity

(CV) of the fastest corticospinal neurons over their cranial

course would reach adult values at approximately 11 months.

The CV of corticospinal neurons in the spinal cord increased

with age but with a slower time course. In the neonate, the

fastest spinal CV was estimated at 7.8 m/sec, approximately

10 times slower than in adults (mean 80.0 m/sec). Our data

predict that full myelination of corticospinal axons in the

spinal cord would not occur until approximately 36 months. No

short-latency EMG responses were elicited in arm and hand

muscles by TMS until 3 months of age; TMS thresholds were

high initially and then fell progressively with age. When

corrected for body size, relative latencies of EMG responses

showed an exponential decrease during the first postnatal

months. Our data are consistent with the hypothesis that fine

finger movements are not observed before functional CM

connections are well established and that rapid changes in the

physiological properties of the corticospinal system coincide

with the period in which precision grip is known to mature (3-

6 months). However, corticospinal development continues long

after simple measures of dexterity indicate functional

maturity, and these changes may contribute to the improved

speed and coordination of skilled hand tasks.

346. Olivier, E.; Edgley, S. A.; Armand, J.; Lemon, R. N. An

electrophysiological study of the postnatal development of the

corticospinal system in the macaque monkey. J-Neurosci. 1997

Jan 1; 17(1): 267-76; ISSN: 0270-6474.

UNITED-STATES. Postnatal development of the corticospinal

system was investigated in 13 macaques using noninvasive

transcranial magnetic stimulation (TMS) of the motor cortex

and direct electrical stimulation of corticospinal axons in the

medullary pyramid and spinal cord. The latency of antidromic

corticospinal volleys evoked from the pyramid and recorded

from the motor cortex decreased dramatically during the first

postnatal months. Our data predict that conduction velocity

(CV) of the fastest corticospinal neurons over their cranial

course would reach adult values at approximately 11 months.

The CV of corticospinal neurons in the spinal cord increased

with age but with a slower time course. In the neonate, the

fastest spinal CV was estimated at 7.8 m/sec, approximately

10 times slower than in adults (mean 80.0 m/sec). Our data

predict that full myelination of corticospinal axons in the

spinal cord would not occur until approximately 36 months. No

short-latency EMG responses were elicited in arm and hand

muscles by TMS until 3 months of age; TMS thresholds were

high initially and then fell progressively with age. When

corrected for body size, relative latencies of EMG responses

showed an exponential decrease during the first postnatal

months. Our data are consistent with the hypothesis that fine

finger movements are not observed before functional CM

connections are well established and that rapid changes in the

physiological properties of the corticospinal system coincide

with the period in which precision grip is known to mature (3-

6 months). However, corticospinal development continues long

after simple measures of dexterity indicate functional

maturity, and these changes may contribute to the improved

speed and coordination of skilled hand tasks.

347. Olson, E. C. Onset of electrical excitability during a period of

circus plasma membrane movements in differentiating Xenopus

neurons. J-Neurosci. 1996 Aug 15; 16(16): 5117-29; ISSN:

0270-6474.

UNITED-STATES. Living neurons are usually first identifiable

in primary cultures at the time of neurite initiation, and

studies of excitability have been restricted largely to the

subsequent period. A morphological early marker is described

that identifies neurons for whole-cell voltage-clamp

recordings before neurite initiation. Video time-lapse

recordings of cultured cells dissociated from neurectoderm of

Xenopus neural plate stage embryos reveal cells demonstrating

circus movements, in which blebs of plasma membrane

propagate around the cell circumference within a period of

several minutes. All neurons demonstrate circus movements

before morphological differentiation; the fraction of cells

exhibiting circus movements that differentiate

morphologically depends on the substrate on which they are

cultured. Blockade of circus activity with cytochalasin B does

not prevent neuronal differentiation. Circus movements are not

neurectoderm-specific because they similarly predict

differentiation of myocytes developing in mesodermal

cultures. Initially inexcitable, neurons develop voltage-

dependent K+, Na+, and Ca2+ currents during the period of

several hours in which they exhibit circus movements. The

early development of depolarization-induced elevations of

[Ca2+]i several hours before morphological differentiation

corresponds to the previously described onset of functionally

significant spontaneous elevations of [Ca2+]i in these neurons

and demonstrates a role for early expression of voltage-

dependent ion channels.. 7440-09-7; 7440-23-5; 7440-70-2;

7447-40-7.

348. Olson, E. C. Onset of electrical excitability during a period of

circus plasma membrane movements in differentiating Xenopus

neurons. J-Neurosci. 1996 Aug 15; 16(16): 5117-29; ISSN:

0270-6474.

UNITED-STATES. Living neurons are usually first identifiable

in primary cultures at the time of neurite initiation, and

studies of excitability have been restricted largely to the

subsequent period. A morphological early marker is described

that identifies neurons for whole-cell voltage-clamp

recordings before neurite initiation. Video time-lapse

recordings of cultured cells dissociated from neurectoderm of

Xenopus neural plate stage embryos reveal cells demonstrating

circus movements, in which blebs of plasma membrane

propagate around the cell circumference within a period of

several minutes. All neurons demonstrate circus movements

before morphological differentiation; the fraction of cells

exhibiting circus movements that differentiate

morphologically depends on the substrate on which they are

cultured. Blockade of circus activity with cytochalasin B does

not prevent neuronal differentiation. Circus movements are not

neurectoderm-specific because they similarly predict

differentiation of myocytes developing in mesodermal

cultures. Initially inexcitable, neurons develop voltage-

dependent K+, Na+, and Ca2+ currents during the period of

several hours in which they exhibit circus movements. The

early development of depolarization-induced elevations of

[Ca2+]i several hours before morphological differentiation

corresponds to the previously described onset of functionally

significant spontaneous elevations of [Ca2+]i in these neurons

and demonstrates a role for early expression of voltage-

dependent ion channels.. 7440-09-7; 7440-23-5; 7440-70-2;

7447-40-7.

349. Otake, K.; Nakamura, Y. Single neurons in Barrington's nucleus

projecting to both the paraventricular thalamic nucleus and

the spinal cord by way of axon collaterals: a double labeling

study in the rat. Neurosci-Lett. 1996 May 10; 209(2): 97-100;

ISSN: 0304-3940.

IRELAND. Barrington's nucleus, a center for the micturition

reflex in the pontine tegmentum, was recently reported to

send projection fibers to the paraventricular thalamic nucleus

(PVT). In the present study, we examined whether or not

Barrington's nucleus neurons projecting to the PVT issue axon

collaterals to the lowest lumbar cord segment (L6) containing

the spinal micturition center. Our retrograde double-labeling

study revealed that a subset of Barrington's nucleus neurons

send projection fibers to both the L6 and the thalamic midline

including the PVT via axon collaterals. Such neurons projecting

directly to the thalamic midline and L6 by way of axon

collaterals were additionally scattered in the locus coeruleus,

subcoeruleus nucleus and sublaterodorsal nucleus.

350. Otake, K.; Nakamura, Y. Single neurons in Barrington's nucleus

projecting to both the paraventricular thalamic nucleus and

the spinal cord by way of axon collaterals: a double labeling

study in the rat. Neurosci-Lett. 1996 May 10; 209(2): 97-100;

ISSN: 0304-3940.

IRELAND. Barrington's nucleus, a center for the micturition

reflex in the pontine tegmentum, was recently reported to

send projection fibers to the paraventricular thalamic nucleus

(PVT). In the present study, we examined whether or not

Barrington's nucleus neurons projecting to the PVT issue axon

collaterals to the lowest lumbar cord segment (L6) containing

the spinal micturition center. Our retrograde double-labeling

study revealed that a subset of Barrington's nucleus neurons

send projection fibers to both the L6 and the thalamic midline

including the PVT via axon collaterals. Such neurons projecting

directly to the thalamic midline and L6 by way of axon

collaterals were additionally scattered in the locus coeruleus,

subcoeruleus nucleus and sublaterodorsal nucleus.

351. Ott, T.; Kaestner, K. H.; Monaghan, A. P.; Schutz, G. The mouse

homolog of the region specific homeotic gene spalt of

Drosophila is expressed in the developing nervous system and

in mesoderm-derived structures. Mech-Dev. 1996 May; 56(1-2):

117-28; ISSN: 0925-4773.

IRELAND. The region specific homeotic gene spalt (sal) of

Drosophila determines the specification of terminal segments.

Its mutation leads to an incomplete transformation of

terminal segments into trunk-like segments. The gene product

is a zinc finger protein with a novel structure. We have

isolated the mouse homolog of the Drosophila spalt gene

(msal). The msal cDNA sequence is similar to its Drosophila

counterpart in that it contains seven C2H2-type zinc finger

motifs grouped into three pairs plus a single zinc finger

closely linked to the middle pair. The two genes exhibit high

sequence similarity in the zinc finger regions and to a lower

extent in the putative transactivation domains. We have

analysed the expression pattern of msal and show that it is

expressed in the developing neuroectoderm of the brain, the

inner ear and the spinal cord and in urogenital ridge-derived

structures such as testis, ovaries and kidneys. A weaker and

transient expression is seen in early embryos in the branchial

arches and in tissues like the notochord, the limb buds and the

heart. Given its role in Drosophila melanogaster and its strong

sequence conservation, this expression pattern suggests an

important role for msal in the development of the nervous

system.. 0; 0; 0; 0.

352. Ott, T.; Kaestner, K. H.; Monaghan, A. P.; Schutz, G. The mouse

homolog of the region specific homeotic gene spalt of

Drosophila is expressed in the developing nervous system and

in mesoderm-derived structures. Mech-Dev. 1996 May; 56(1-2):

117-28; ISSN: 0925-4773.

IRELAND. The region specific homeotic gene spalt (sal) of

Drosophila determines the specification of terminal segments.

Its mutation leads to an incomplete transformation of

terminal segments into trunk-like segments. The gene product

is a zinc finger protein with a novel structure. We have

isolated the mouse homolog of the Drosophila spalt gene

(msal). The msal cDNA sequence is similar to its Drosophila

counterpart in that it contains seven C2H2-type zinc finger

motifs grouped into three pairs plus a single zinc finger

closely linked to the middle pair. The two genes exhibit high

sequence similarity in the zinc finger regions and to a lower

extent in the putative transactivation domains. We have

analysed the expression pattern of msal and show that it is

expressed in the developing neuroectoderm of the brain, the

inner ear and the spinal cord and in urogenital ridge-derived

structures such as testis, ovaries and kidneys. A weaker and

transient expression is seen in early embryos in the branchial

arches and in tissues like the notochord, the limb buds and the

heart. Given its role in Drosophila melanogaster and its strong

sequence conservation, this expression pattern suggests an

important role for msal in the development of the nervous

system.. 0; 0; 0; 0.

353. Parenti, R.; Cicirata, F.; Panto, M. R.; Serapide, M. F. The

projections of the lateral reticular nucleus to the deep

cerebellar nuclei. An experimental analysis in the rat. Eur-J-

Neurosci. 1996 Oct; 8(10): 2157-67; ISSN: 0953-816X.

ENGLAND. The projections of the lateral reticular nucleus

(LRN) to the cerebellar nuclei were studied using the

retrograde axonal transport of tetramethyl rhodamine dextran

amine (10% solution in 0.01 M neutral phosphate buffer) in 19

adult Wistar strain rats. The cerebellar nuclei receive

topographically organized projections from the LRN. The

projections are bilateral with an ipsilateral predominance and

they are symmetrical. The contralateral component is

progressively larger for projections to the nuclei

interpositalis, to the nucleus lateralis and to the nucleus

medialis. The projections to the various cerebellar nuclei

arise from rostrocaudally oriented columns of neurons located

in different (partly overlapping) areas of the magnocellular

division of the LRN. The nucleus lateralis receives terminals

from the dorsomedial area (mainly from the rostral level of

the LRN), the nuclei interpositalis from the dorsolateral area

(mainly from the central level) and the nucleus medialis from

the intermedioventral area (mainly from the caudal level).

Afferent fibres from the small subtrigeminal division were

traced to the three cerebellar nuclei and from the

parvocellular division to the nuclei interpositalis and

medialis. The density of the projections from the LRN to the

nuclei interpositalis increases progressively with the shift of

the terminal field from the rostrolateral to the caudomedial

part of the nucleus. The projections to the nucleus lateralis

reach principally the dorsolateral hump, whereas only a few

neurons project to the other divisions (parvo- and

magnocellular). The projections to the various regions of the

nucleus medialis show different densities. The highest density

was found for projections to the caudal part, in particular to

the dorsolateral protuberance and to the ventrolateral area of

the middle division. Conversely, a low density of projections

was found for the other areas of the middle division. The

regions of the magnocellular division of the LRN which project

to the nuclei lateralis (and are thus related to the cerebral

cortex), interpositalis (related to the red nucleus) and

medialis (related to the spinal cord) also receive afferent

terminals from the cerebral cortex, the red nucleus and the

spinal cord respectively, in addition to various afferent inputs.

Thus, each of these areas is apparently concerned with

integrating some spinal and supraspinal information in

reverberating circuits.

354. Parenti, R.; Cicirata, F.; Panto, M. R.; Serapide, M. F. The

projections of the lateral reticular nucleus to the deep

cerebellar nuclei. An experimental analysis in the rat. Eur-J-

Neurosci. 1996 Oct; 8(10): 2157-67; ISSN: 0953-816X.

ENGLAND. The projections of the lateral reticular nucleus

(LRN) to the cerebellar nuclei were studied using the

retrograde axonal transport of tetramethyl rhodamine dextran

amine (10% solution in 0.01 M neutral phosphate buffer) in 19

adult Wistar strain rats. The cerebellar nuclei receive

topographically organized projections from the LRN. The

projections are bilateral with an ipsilateral predominance and

they are symmetrical. The contralateral component is

progressively larger for projections to the nuclei

interpositalis, to the nucleus lateralis and to the nucleus

medialis. The projections to the various cerebellar nuclei

arise from rostrocaudally oriented columns of neurons located

in different (partly overlapping) areas of the magnocellular

division of the LRN. The nucleus lateralis receives terminals

from the dorsomedial area (mainly from the rostral level of

the LRN), the nuclei interpositalis from the dorsolateral area

(mainly from the central level) and the nucleus medialis from

the intermedioventral area (mainly from the caudal level).

Afferent fibres from the small subtrigeminal division were

traced to the three cerebellar nuclei and from the

parvocellular division to the nuclei interpositalis and

medialis. The density of the projections from the LRN to the

nuclei interpositalis increases progressively with the shift of

the terminal field from the rostrolateral to the caudomedial

part of the nucleus. The projections to the nucleus lateralis

reach principally the dorsolateral hump, whereas only a few

neurons project to the other divisions (parvo- and

magnocellular). The projections to the various regions of the

nucleus medialis show different densities. The highest density

was found for projections to the caudal part, in particular to

the dorsolateral protuberance and to the ventrolateral area of

the middle division. Conversely, a low density of projections

was found for the other areas of the middle division. The

regions of the magnocellular division of the LRN which project

to the nuclei lateralis (and are thus related to the cerebral

cortex), interpositalis (related to the red nucleus) and

medialis (related to the spinal cord) also receive afferent

terminals from the cerebral cortex, the red nucleus and the

spinal cord respectively, in addition to various afferent inputs.

Thus, each of these areas is apparently concerned with

integrating some spinal and supraspinal information in

reverberating circuits.

355. Patel, M. R.; Louie, W.; Rachlin, J. Postoperative cerebrospinal

fluid leaks of the lumbosacral spine: management with

percutaneous fibrin glue. AJNR-Am-J-Neuroradiol. 1996 Mar;

17(3): 495-500; ISSN: 0195-6108.

UNITED-STATES. PURPOSE: To assess CT-guided injection of

fibrin glue for the management of lumbosacral cerebrospinal

fluid (CSF) leaks. METHODS: Six consecutive patients with

postoperative CSF leaks were treated after CSF aspiration

under CT guidance. A solution of cryoprecipitate was

simultaneously injected with a 10% calcium chloride solution

containing 2000 units of thrombin per milliliter. In one

patient, 0.5 mL of iopamidol was added to the calcium

chloride/thrombin mixture before injection. Placement of the

fibrin glue aggregate was confirmed by CT imaging. To

determine outcomes we reviewed the patients' records,

postprocedure imaging studies, and physical findings, and we

interviewed the patients directly. RESULTS: In three patients

with postoperative CSF leaks, symptoms resolved after

treatment. Despite imaging evidence of successful plug

deployment, two other patients still had severe symptoms, and

they underwent surgery after 2 and 18 hours, respectively. One

patient had a continued CSF leak and a headache after 12

hours; follow-up surgery repaired an unsuspected dural tear

just distal to the site of original surgery underneath the

lamina and not covered by the fibrin glue. After one of the

successful procedures, the patient had a fever and a headache,

probably because of aseptic meningitis, which resolved after 2

days. CONCLUSION: Percutaneous CT-guided placement of fibrin

glue may provide nonsurgical treatment for postoperative CSF

leaks, potentially avoiding a major and technically difficult

surgical procedure.. 0.

356. Patel, M. R.; Louie, W.; Rachlin, J. Postoperative cerebrospinal

fluid leaks of the lumbosacral spine: management with

percutaneous fibrin glue. AJNR-Am-J-Neuroradiol. 1996 Mar;

17(3): 495-500; ISSN: 0195-6108.

UNITED-STATES. PURPOSE: To assess CT-guided injection of

fibrin glue for the management of lumbosacral cerebrospinal

fluid (CSF) leaks. METHODS: Six consecutive patients with

postoperative CSF leaks were treated after CSF aspiration

under CT guidance. A solution of cryoprecipitate was

simultaneously injected with a 10% calcium chloride solution

containing 2000 units of thrombin per milliliter. In one

patient, 0.5 mL of iopamidol was added to the calcium

chloride/thrombin mixture before injection. Placement of the

fibrin glue aggregate was confirmed by CT imaging. To

determine outcomes we reviewed the patients' records,

postprocedure imaging studies, and physical findings, and we

interviewed the patients directly. RESULTS: In three patients

with postoperative CSF leaks, symptoms resolved after

treatment. Despite imaging evidence of successful plug

deployment, two other patients still had severe symptoms, and

they underwent surgery after 2 and 18 hours, respectively. One

patient had a continued CSF leak and a headache after 12

hours; follow-up surgery repaired an unsuspected dural tear

just distal to the site of original surgery underneath the

lamina and not covered by the fibrin glue. After one of the

successful procedures, the patient had a fever and a headache,

probably because of aseptic meningitis, which resolved after 2

days. CONCLUSION: Percutaneous CT-guided placement of fibrin

glue may provide nonsurgical treatment for postoperative CSF

leaks, potentially avoiding a major and technically difficult

surgical procedure.. 0.

357. Pernas Alonso, R.; Schaffner, A. E.; Perrone Capano, C.; Orlando, A.;

Morelli, F.; Hansen, C. T.; Barker, J. L.; Esposito, B.; Cacucci, F.;

di Porzio, U. Early upregulation of medium neurofilament gene

expression in developing spinal cord of the wobbler mouse

mutant. Brain-Res-Mol-Brain-Res. 1996 Jun; 38(2): 267-75;

ISSN: 0169-328X.

NETHERLANDS. Homozygous wobbler mouse mutants develop a

progressive paralysis due to spinal motoneuron degeneration.

To understand the molecular aspect underlying the genetic

defect we have studied the embryonic (from E13) and postnatal

expression of the three neurofilament and choline

acetyltransferase genes in each member from several wild-

type (wt) and wobbler (wr) progenies. There are no variations

among wt littermates at all ages studied. In contrast, analyses

of neurofilament mRNA reveals a 3-4-fold increase of medium

neurofilament (NFM) mRNA in wobbler mice (wr/wr). The

pattern of increased NFM mRNA during development, prior to

the appearance of the wobbler phenotype, among littermates

(from heterozygous carriers) conforms to a mendelian

inheritance of a single gene defect 1:2:1 (wr/wr:wr/+:+/+).

Light and heavy neurofilament mRNA levels are also increased

later in development exclusively in those individuals with high

NFM mRNA values indicating that increase of the latter is

associated with increase of the light and heavy subunit

expression. Also NF proteins are increased. Expression of

choline acetyltransferase gene is instead always comparable

to normal control. Our study provides novel insights into the

nature of the wobbler defect, strengthening the hypothesis

that neurofilament accumulation plays a pivotal role in the

etiopathogenesis of motoneuron degeneration.. EC 2.3.1.6; 0.

358. Pernas Alonso, R.; Schaffner, A. E.; Perrone Capano, C.; Orlando, A.;

Morelli, F.; Hansen, C. T.; Barker, J. L.; Esposito, B.; Cacucci, F.;

di Porzio, U. Early upregulation of medium neurofilament gene

expression in developing spinal cord of the wobbler mouse

mutant. Brain-Res-Mol-Brain-Res. 1996 Jun; 38(2): 267-75;

ISSN: 0169-328X.

NETHERLANDS. Homozygous wobbler mouse mutants develop a

progressive paralysis due to spinal motoneuron degeneration.

To understand the molecular aspect underlying the genetic

defect we have studied the embryonic (from E13) and postnatal

expression of the three neurofilament and choline

acetyltransferase genes in each member from several wild-

type (wt) and wobbler (wr) progenies. There are no variations

among wt littermates at all ages studied. In contrast, analyses

of neurofilament mRNA reveals a 3-4-fold increase of medium

neurofilament (NFM) mRNA in wobbler mice (wr/wr). The

pattern of increased NFM mRNA during development, prior to

the appearance of the wobbler phenotype, among littermates

(from heterozygous carriers) conforms to a mendelian

inheritance of a single gene defect 1:2:1 (wr/wr:wr/+:+/+).

Light and heavy neurofilament mRNA levels are also increased

later in development exclusively in those individuals with high

NFM mRNA values indicating that increase of the latter is

associated with increase of the light and heavy subunit

expression. Also NF proteins are increased. Expression of

choline acetyltransferase gene is instead always comparable

to normal control. Our study provides novel insights into the

nature of the wobbler defect, strengthening the hypothesis

that neurofilament accumulation plays a pivotal role in the

etiopathogenesis of motoneuron degeneration.. EC 2.3.1.6; 0.

359. Petrov, E. S.; Varlinskaya, E. I.; Smotherman, W. P. Interactions

between vasopressin and mu-opioid systems in the rat fetus.

Physiol-Behav. 1996 Jul; 60(1): 217-30; ISSN: 0031-9384.

UNITED-STATES. Administration of arginine-vasopressin

(AVP) into the cisterna magna (IC injection) of the E20 rat

fetus increases motor activity and promotes expression of

rare patterns of behavior including mouthing, licking, and

facial wiping. These effects are mediated by V1 receptors in

the brain stem and spinal cord. In this study, AVP-induced

changes in motor behavior were measured to characterize

interactions within the AVP system and between the AVP and

mu-opioid systems in the fetal rat. Injection of AVP into the

brain hemispheres (IH injection) diminished the effects of an

IC injection of AVP. AVP effects were potentiated by blockade

of hemispheric V1 receptors, suggesting that hemispheric V1

receptors inhibit V1 receptor-containing neurons in the brain

stem and spinal cord. Intracisternal injection of the mu

agonist DAGO suppressed the effects of AVP whereas blockade

of mu-opioid receptors in the brain stem and spinal cord with

CTOP and activation of mu receptors in the hemispheres with

DAGO potentiated the behavioral effects of AVP. The

behavioral effects of AVP are mediated by V1 receptors in the

brain stem and spinal cord and may be under the inhibitory

control of a mu-opioid system localized at the same level of

the brain. Facilitation of AVP effects following IH injection of

DAGO may involve an inhibition of the inhibitory effects of V1

receptor-containing neurons located in the hemispheres.

Interactions between mu-opioid and AVP systems in the caudal

and rostral portions of the fetal brain may be based on a

common principle.. 0; 113-79-1.

360. Petrov, E. S.; Varlinskaya, E. I.; Smotherman, W. P. Interactions

between vasopressin and mu-opioid systems in the rat fetus.

Physiol-Behav. 1996 Jul; 60(1): 217-30; ISSN: 0031-9384.

UNITED-STATES. Administration of arginine-vasopressin

(AVP) into the cisterna magna (IC injection) of the E20 rat

fetus increases motor activity and promotes expression of

rare patterns of behavior including mouthing, licking, and

facial wiping. These effects are mediated by V1 receptors in

the brain stem and spinal cord. In this study, AVP-induced

changes in motor behavior were measured to characterize

interactions within the AVP system and between the AVP and

mu-opioid systems in the fetal rat. Injection of AVP into the

brain hemispheres (IH injection) diminished the effects of an

IC injection of AVP. AVP effects were potentiated by blockade

of hemispheric V1 receptors, suggesting that hemispheric V1

receptors inhibit V1 receptor-containing neurons in the brain

stem and spinal cord. Intracisternal injection of the mu

agonist DAGO suppressed the effects of AVP whereas blockade

of mu-opioid receptors in the brain stem and spinal cord with

CTOP and activation of mu receptors in the hemispheres with

DAGO potentiated the behavioral effects of AVP. The

behavioral effects of AVP are mediated by V1 receptors in the

brain stem and spinal cord and may be under the inhibitory

control of a mu-opioid system localized at the same level of

the brain. Facilitation of AVP effects following IH injection of

DAGO may involve an inhibition of the inhibitory effects of V1

receptor-containing neurons located in the hemispheres.

Interactions between mu-opioid and AVP systems in the caudal

and rostral portions of the fetal brain may be based on a

common principle.. 0; 113-79-1.

361. Pierrot Deseilligny, E. Transmission of the cortical command for

human voluntary movement through cervical propriospinal

premotoneurons. Prog-Neurobiol. 1996 Mar; 48(4-5): 489-517;

ISSN: 0301-0082.

ENGLAND. In man there is now strong evidence for the

existence of a system of cervical propriospinal

premotoneurons interposed in the corticospinal pathway to

upper limb motoneurons. The relevant neurons are located

rostral to upper limb motoneurons. They receive both weak

excitation and strong inhibition from low threshold afferents

in the upper limb. Ongoing EMG activity recorded in wrist and

elbow extensors during voluntary movements of different

types (tonic contraction, reaching) is suppressed by a

cutaneous volley evoked by stimulation of the superficial

radial nerve. There is evidence that this cutaneous-induced

suppression is due to inhibition of transmission of the cortical

command in the system of cervical propriospinal

premotoneurons, thus indicating that part of the descending

command for movement reaches the relevant motoneurons via

these premotoneurons. In patients with hemiplegia, the

cutaneous-induced depression of ongoing EMG activity is

significantly larger on the hemiplegic side. This suggests that

the mechanisms underlying residual motricity after a lesion of

the corticospinal tract involve the system of propriospinal

premotoneurons.

362. Pierrot Deseilligny, E. Transmission of the cortical command for

human voluntary movement through cervical propriospinal

premotoneurons. Prog-Neurobiol. 1996 Mar; 48(4-5): 489-517;

ISSN: 0301-0082.

ENGLAND. In man there is now strong evidence for the

existence of a system of cervical propriospinal

premotoneurons interposed in the corticospinal pathway to

upper limb motoneurons. The relevant neurons are located

rostral to upper limb motoneurons. They receive both weak

excitation and strong inhibition from low threshold afferents

in the upper limb. Ongoing EMG activity recorded in wrist and

elbow extensors during voluntary movements of different

types (tonic contraction, reaching) is suppressed by a

cutaneous volley evoked by stimulation of the superficial

radial nerve. There is evidence that this cutaneous-induced

suppression is due to inhibition of transmission of the cortical

command in the system of cervical propriospinal

premotoneurons, thus indicating that part of the descending

command for movement reaches the relevant motoneurons via

these premotoneurons. In patients with hemiplegia, the

cutaneous-induced depression of ongoing EMG activity is

significantly larger on the hemiplegic side. This suggests that

the mechanisms underlying residual motricity after a lesion of

the corticospinal tract involve the system of propriospinal

premotoneurons.

363. Pitts, A. F.; Miller, M. W. Expression of nerve growth factor, p75,

and trk in the somatosensory and motor cortices of mature

rats: evidence for local trophic support circuits. Somatosens-

Mot-Res. 1995; 12(3-4): 329-42; ISSN: 0899-0220.

ENGLAND. Neurotrophins such as nerve growth factor (NGF) are

critical for the maintenance of CNS neurons. We determined

the expression of NGF and the neurotrophin receptors p75 and

trk in the somatosensory and motor cortices of mature rats

with immunohistochemical techniques. Sections of mature rat

cortex were processed immunohistochemically with primary

antibodies directed against NGF, p75, or trk. The distribution

of immunoreactive elements was examined, and stereological

techniques were used to determine the density and size of

immunoreactive cell bodies. Some sections processed for trk

immunoreactivity were examined with an electron microscope.

From the size and morphology of the labeled cells, it appeared

that only neurons in the gray matter were NGF-positive. NGF

was detected in one-third of the neurons in layers II-III, V,

and VI of both somatosensory cortex and motor cortex;

however, fewer than 1 in 12 of the layer IV neurons was NGF-

positive. With the notable exception of layer V, few cell bodies

(2-10% of the total population) were p75- or trk-

immunoreactive. Layer Vb was replete with receptor-positive

cell bodies; more than one-third of the layer Vb neurons were

p75- or trk-positive. All labeled cells appeared to be

pyramidal neurons. The distribution of p75 labeling with the

two anti-p75 antibodies was indistinguishable. In addition, the

neuropil in the supragranular laminae was p75- or trk-

positive. Electron microscopy showed that trk

immunoreactivity was also expressed by dendrites. Only rarely

were immunoreactive axons detected. In summary, NGF is

expressed by cortical neurons throughout cortex, and

neurotrophin receptors are widely produced by postsynaptic

targets. Thus, NGF appears to participate in an intracortical

autoregulatory system. The strong expression of neurotrophin

receptors by pyramidal neurons in layer Vb (the origin of

brainstem and spinal cord projections) suggests that the

neurotrophins are especially critical for the regulation of

corticofugal projection systems.. 0; 0.

364. Pitts, A. F.; Miller, M. W. Expression of nerve growth factor, p75,

and trk in the somatosensory and motor cortices of mature

rats: evidence for local trophic support circuits. Somatosens-

Mot-Res. 1995; 12(3-4): 329-42; ISSN: 0899-0220.

ENGLAND. Neurotrophins such as nerve growth factor (NGF) are

critical for the maintenance of CNS neurons. We determined

the expression of NGF and the neurotrophin receptors p75 and

trk in the somatosensory and motor cortices of mature rats

with immunohistochemical techniques. Sections of mature rat

cortex were processed immunohistochemically with primary

antibodies directed against NGF, p75, or trk. The distribution

of immunoreactive elements was examined, and stereological

techniques were used to determine the density and size of

immunoreactive cell bodies. Some sections processed for trk

immunoreactivity were examined with an electron microscope.

From the size and morphology of the labeled cells, it appeared

that only neurons in the gray matter were NGF-positive. NGF

was detected in one-third of the neurons in layers II-III, V,

and VI of both somatosensory cortex and motor cortex;

however, fewer than 1 in 12 of the layer IV neurons was NGF-

positive. With the notable exception of layer V, few cell bodies

(2-10% of the total population) were p75- or trk-

immunoreactive. Layer Vb was replete with receptor-positive

cell bodies; more than one-third of the layer Vb neurons were

p75- or trk-positive. All labeled cells appeared to be

pyramidal neurons. The distribution of p75 labeling with the

two anti-p75 antibodies was indistinguishable. In addition, the

neuropil in the supragranular laminae was p75- or trk-

positive. Electron microscopy showed that trk

immunoreactivity was also expressed by dendrites. Only rarely

were immunoreactive axons detected. In summary, NGF is

expressed by cortical neurons throughout cortex, and

neurotrophin receptors are widely produced by postsynaptic

targets. Thus, NGF appears to participate in an intracortical

autoregulatory system. The strong expression of neurotrophin

receptors by pyramidal neurons in layer Vb (the origin of

brainstem and spinal cord projections) suggests that the

neurotrophins are especially critical for the regulation of

corticofugal projection systems.. 0; 0.

365. Podnar, S.; Vodusek, D. B.; Trsinar, B. Mechanically evoked

bulbocavernosus reflex and pudendal somatosensory responses

in children. Pflugers-Arch. 1996; 431(6 Suppl 2): R293-4;

ISSN: 0031-6768.

GERMANY. Electrophysiological investigations of sacral

functions are unpleasant and as such rarely performed in

children. A novel approach is presented: bulbocavernosus reflex

and pudendal cortical somatosensory evoked potentials were

studied on mechanical stimulation of the penis and compared

with their electrically evoked counterparts in 21 (5-14 years

old) boys. An electromechanical hammer was used and only

surface electrodes applied. Children preferred mechanical

stimulation which also evoked reliable responses in more boys.

Reflex responses on mechanical stimulation were found to be

of longer latency, however no latency differences between

cortical evoked responses to either stimulation were found.

We suggest the use of mechanical stimulation in

uroneurophysiological testing of children.

366. Podnar, S.; Vodusek, D. B.; Trsinar, B. Mechanically evoked

bulbocavernosus reflex and pudendal somatosensory responses

in children. Pflugers-Arch. 1996; 431(6 Suppl 2): R293-4;

ISSN: 0031-6768.

GERMANY. Electrophysiological investigations of sacral

functions are unpleasant and as such rarely performed in

children. A novel approach is presented: bulbocavernosus reflex

and pudendal cortical somatosensory evoked potentials were

studied on mechanical stimulation of the penis and compared

with their electrically evoked counterparts in 21 (5-14 years

old) boys. An electromechanical hammer was used and only

surface electrodes applied. Children preferred mechanical

stimulation which also evoked reliable responses in more boys.

Reflex responses on mechanical stimulation were found to be

of longer latency, however no latency differences between

cortical evoked responses to either stimulation were found.

We suggest the use of mechanical stimulation in

uroneurophysiological testing of children.

367. Popovich, P. G.; Horner, P. J.; Mullin, B. B.; Stokes, B. T. A

quantitative spatial analysis of the blood-spinal cord barrier.

I. Permeability changes after experimental spinal contusion

injury. Exp-Neurol. 1996 Dec; 142(2): 258-75; ISSN: 0014-

4886.

UNITED-STATES. Blood-spinal cord barrier (BSB) permeability

was measured using quantitative autoradiography following

contusion injury to the rat spinal cord. Permeability was

assessed by calculating blood-to-tissue transfer constants (Ki

values) for the vascular tracer [14C]-alpha-aminoisobutyric

acid (AIB) in injured (3, 7, 14, and 28 days postinjury),

laminectomy control, and uninjured control animals.

Permeability was quantitated using four separate imaging

techniques in gray and white matter throughout the rostro-

caudal extents of the forming lesion. Away from the epicenter,

gray matter permeability was further differentiated within

discrete spinal lamina using computerized templates.

Regardless of the type of analysis used, increased AIB

permeability (Ki values) was noted at all survival times in all

tissue regions with respect to both uninjured and laminectomy

control groups. The data indicate a large increase in individual

Ki values throughout the dorsoventral axis of the spinal cord

at 3 days postinjury (approximately 6-9 ml/kg/min). By 7

days, Ki values were quantitatively smaller (approximately 4-

5 ml/kg/min) in all regions compared with 3-day tissues.

Despite further attenuation of AIB uptake in the gray matter at

14 and 28 days postinjury, circumferential white matter

tracts showed a secondary increase in permeability compared

to 7-day tissue. Permeability in the white matter at 14-28

days postinjury (approximately 5-6 ml/kg/min) was

comparable to that at 3 days postinjury (6-7 ml/kg/min).

Measurements of the axial distribution of AIB permeability

indicate increased BSB permeability over several segments

rostral and caudal to the lesion epicenter (approximately 3 cm

in both directions). Secondary elevations of AIB transfer in the

spinal white matter between 14 and 28 days were colocalized

with zones of immunohistochemically defined microglial

clusters. The known plasticity of this cell type in response to

changes in the extracellular microenvironment suggests that

the spinal white matter at later survival times (14-28 days

postinjury) is an area of dynamic vascular and/or axonal

reconstruction. The implications of increased permeability to

both tissue injury and neural regeneration are discussed.. 0; 0;

62-57-7.

368. Popovich, P. G.; Horner, P. J.; Mullin, B. B.; Stokes, B. T. A

quantitative spatial analysis of the blood-spinal cord barrier.

I. Permeability changes after experimental spinal contusion

injury. Exp-Neurol. 1996 Dec; 142(2): 258-75; ISSN: 0014-

4886.

UNITED-STATES. Blood-spinal cord barrier (BSB) permeability

was measured using quantitative autoradiography following

contusion injury to the rat spinal cord. Permeability was

assessed by calculating blood-to-tissue transfer constants (Ki

values) for the vascular tracer [14C]-alpha-aminoisobutyric

acid (AIB) in injured (3, 7, 14, and 28 days postinjury),

laminectomy control, and uninjured control animals.

Permeability was quantitated using four separate imaging

techniques in gray and white matter throughout the rostro-

caudal extents of the forming lesion. Away from the epicenter,

gray matter permeability was further differentiated within

discrete spinal lamina using computerized templates.

Regardless of the type of analysis used, increased AIB

permeability (Ki values) was noted at all survival times in all

tissue regions with respect to both uninjured and laminectomy

control groups. The data indicate a large increase in individual

Ki values throughout the dorsoventral axis of the spinal cord

at 3 days postinjury (approximately 6-9 ml/kg/min). By 7

days, Ki values were quantitatively smaller (approximately 4-

5 ml/kg/min) in all regions compared with 3-day tissues.

Despite further attenuation of AIB uptake in the gray matter at

14 and 28 days postinjury, circumferential white matter

tracts showed a secondary increase in permeability compared

to 7-day tissue. Permeability in the white matter at 14-28

days postinjury (approximately 5-6 ml/kg/min) was

comparable to that at 3 days postinjury (6-7 ml/kg/min).

Measurements of the axial distribution of AIB permeability

indicate increased BSB permeability over several segments

rostral and caudal to the lesion epicenter (approximately 3 cm

in both directions). Secondary elevations of AIB transfer in the

spinal white matter between 14 and 28 days were colocalized

with zones of immunohistochemically defined microglial

clusters. The known plasticity of this cell type in response to

changes in the extracellular microenvironment suggests that

the spinal white matter at later survival times (14-28 days

postinjury) is an area of dynamic vascular and/or axonal

reconstruction. The implications of increased permeability to

both tissue injury and neural regeneration are discussed.. 0; 0;

62-57-7.

369. Portillo, F.; Carrasco, M.; Vallo, J. J. Hypothalamic neuron

projection to autonomic preganglionic levels related with

glucose metabolism: a fluorescent labelling study in the rat.

Neurosci-Lett. 1996 Jun 7; 210(3): 197-200; ISSN: 0304-3940.

IRELAND. The location of hypothalamic paraventricular

neurons projecting to sympathetic preganglionic levels and

related to the autonomic regulation of various organs involved

in glucose metabolism (OGM) was determined by ipsilateral

injections of two fluorescent tracers, Diamidino Yellow into

the left dorsal motor nucleus of the vagus and Fast Blue into

the left intermediolateral cell column of the T8-T9 spinal

cord. Hypothalamospinal neurons were mainly located in the

dorsal part of the paraventricular hypothalamic nucleus (PVH)

and the hypothalamobulbar neurons were most abundant in the

ventral, medial and extreme lateral parts of the PVH. No

double-labelled neurons were found in the hypothalamus. These

results can help the knowledge of the neural hypothalamic

network related with the autonomic hypothalamic control.. EC

1.11.1.-; 0; 50-99-7.

370. Portillo, F.; Carrasco, M.; Vallo, J. J. Hypothalamic neuron

projection to autonomic preganglionic levels related with

glucose metabolism: a fluorescent labelling study in the rat.

Neurosci-Lett. 1996 Jun 7; 210(3): 197-200; ISSN: 0304-3940.

IRELAND. The location of hypothalamic paraventricular

neurons projecting to sympathetic preganglionic levels and

related to the autonomic regulation of various organs involved

in glucose metabolism (OGM) was determined by ipsilateral

injections of two fluorescent tracers, Diamidino Yellow into

the left dorsal motor nucleus of the vagus and Fast Blue into

the left intermediolateral cell column of the T8-T9 spinal

cord. Hypothalamospinal neurons were mainly located in the

dorsal part of the paraventricular hypothalamic nucleus (PVH)

and the hypothalamobulbar neurons were most abundant in the

ventral, medial and extreme lateral parts of the PVH. No

double-labelled neurons were found in the hypothalamus. These

results can help the knowledge of the neural hypothalamic

network related with the autonomic hypothalamic control.. EC

1.11.1.-; 0; 50-99-7.

371. Prasad, V. S.; Reddy, D. R.; Murty, J. M. Cervico-thoracic

neurenteric cyst: clinicoradiological correlation with

embryogenesis. Childs-Nerv-Syst. 1996 Jan; 12(1): 48-51;

ISSN: 0256-7040.

GERMANY. Two cases of cervico-dorsal neurenteric cysts are

presented, one located dorsal and the other ventral to the

spinal cord, with associated Klippel-Feil anomaly,

meningocele, spinal dysraphism and possibly spinal cord

malformation. One patient was operated on as a neonate for a

cervico-thoracic meningocele and presented during

adolescence with spastic quadriparesis. Imaging revealed

spina bifida, a dorsally located neurenteric cyst and a

tendency towards split cord malformation. The other child

presented with cervico-thoracic kyphoscoliosis and

paraparesis. Imaging demonstrated persistence of a cervico-

thoracic remnant of the primitive neurenteric canal through

the upper thoracic spine.

372. Prasad, V. S.; Reddy, D. R.; Murty, J. M. Cervico-thoracic

neurenteric cyst: clinicoradiological correlation with

embryogenesis. Childs-Nerv-Syst. 1996 Jan; 12(1): 48-51;

ISSN: 0256-7040.

GERMANY. Two cases of cervico-dorsal neurenteric cysts are

presented, one located dorsal and the other ventral to the

spinal cord, with associated Klippel-Feil anomaly,

meningocele, spinal dysraphism and possibly spinal cord

malformation. One patient was operated on as a neonate for a

cervico-thoracic meningocele and presented during

adolescence with spastic quadriparesis. Imaging revealed

spina bifida, a dorsally located neurenteric cyst and a

tendency towards split cord malformation. The other child

presented with cervico-thoracic kyphoscoliosis and

paraparesis. Imaging demonstrated persistence of a cervico-

thoracic remnant of the primitive neurenteric canal through

the upper thoracic spine.

373. Prentice, T. W.; Joynes, R. L.; Meagher, M. W.; Grau, J. W. Impact of

shock on pain reactivity: III. The magnitude of hypoalgesia

observed depends on test location. Behav-Neurosci. 1996 Jun;

110(3): 528-41; ISSN: 0735-7044.

UNITED-STATES. Pain reactivity is often assessed in rodents

by measuring the latency of tail withdrawal from radiant heat

(the tail-flick test). Using this test, the authors show that the

magnitude of antinociception observed in spinal rats depends

on test location; antinociception is observed at, and distal to,

where shock is applied, but not at more proximal sites

(Experiments 1 & 2). Experiment 3 evaluates the generality of

this observation by testing 3 other shock schedules that are

known to elicit distinct forms of antinociception. In all but 1

case, the magnitude of antinociception varied as a function of

test location. Experiment 4 shows that morphine also has a

greater impact at distal test locations. Experiment 5 assessed

the impact of tailshock on reactivity to radiant heat applied to

the foot. Of the 5 distinct forms of shock-induced

antinociception studied, only 2 produce a robust

antinociception at this test location.

374. Prentice, T. W.; Joynes, R. L.; Meagher, M. W.; Grau, J. W. Impact of

shock on pain reactivity: III. The magnitude of hypoalgesia

observed depends on test location. Behav-Neurosci. 1996 Jun;

110(3): 528-41; ISSN: 0735-7044.

UNITED-STATES. Pain reactivity is often assessed in rodents

by measuring the latency of tail withdrawal from radiant heat

(the tail-flick test). Using this test, the authors show that the

magnitude of antinociception observed in spinal rats depends

on test location; antinociception is observed at, and distal to,

where shock is applied, but not at more proximal sites

(Experiments 1 & 2). Experiment 3 evaluates the generality of

this observation by testing 3 other shock schedules that are

known to elicit distinct forms of antinociception. In all but 1

case, the magnitude of antinociception varied as a function of

test location. Experiment 4 shows that morphine also has a

greater impact at distal test locations. Experiment 5 assessed

the impact of tailshock on reactivity to radiant heat applied to

the foot. Of the 5 distinct forms of shock-induced

antinociception studied, only 2 produce a robust

antinociception at this test location.

375. Price, R. E.; Tinkey, P. T.; Leeds, N. E.; Hazle, J. D.; Langford, L. A.;

Stephens, L. C.; Ang, K. K. Glioblastoma multiforme arising in

the irradiated spinal cord of a rhesus monkey (Macaca

mulatta). J-Med-Primatol. 1996 Apr; 25(2): 140-5; ISSN:

0047-2565.

DENMARK. An adult female rhesus monkey that had received

44.0 Gy of cobalt 60 radiation to 8 cm of the cervical and

upper thoracic spinal cord approximately 2.8 years

postirradiation developed a sudden onset of self-mutilation

and loss of function of the right arm followed progressively by

loss of function of the left arm and terminally bilateral

paresis of the legs. Histopathologic examination of the

cervical spinal cord revealed a glioblastoma multiforme that

extended from the cervical medullary junction to the sixth

cervical vertebrae. Because of the infrequent occurrence of

spontaneous neoplasia in rhesus monkeys and the location in

the radiation field, the glioblastoma is believed to be

radiation induced.. 0; 0; 67-43-6; 7440-54-2; 80529-93-7.

376. Price, R. E.; Tinkey, P. T.; Leeds, N. E.; Hazle, J. D.; Langford, L. A.;

Stephens, L. C.; Ang, K. K. Glioblastoma multiforme arising in

the irradiated spinal cord of a rhesus monkey (Macaca

mulatta). J-Med-Primatol. 1996 Apr; 25(2): 140-5; ISSN:

0047-2565.

DENMARK. An adult female rhesus monkey that had received

44.0 Gy of cobalt 60 radiation to 8 cm of the cervical and

upper thoracic spinal cord approximately 2.8 years

postirradiation developed a sudden onset of self-mutilation

and loss of function of the right arm followed progressively by

loss of function of the left arm and terminally bilateral

paresis of the legs. Histopathologic examination of the

cervical spinal cord revealed a glioblastoma multiforme that

extended from the cervical medullary junction to the sixth

cervical vertebrae. Because of the infrequent occurrence of

spontaneous neoplasia in rhesus monkeys and the location in

the radiation field, the glioblastoma is believed to be

radiation induced.. 0; 0; 67-43-6; 7440-54-2; 80529-93-7.

377. Pringle, R. G. Traumatic spinal cord injuries in Istanbul [letter].

Spinal-Cord. 1996 Aug; 34(8): 498; ISSN: 1362-4393.

ENGLAND.

378. Pringle, R. G. Traumatic spinal cord injuries in Istanbul [letter].

Spinal-Cord. 1996 Aug; 34(8): 498; ISSN: 1362-4393.

ENGLAND.

379. Pugh, G. Jr; Smith, P. B.; Dombrowski, D. S.; Welch, S. P. The role of

endogenous opioids in enhancing the antinociception produced

by the combination of delta 9-tetrahydrocannabinol and

morphine in the spinal cord. J-Pharmacol-Exp-Ther. 1996 Nov;

279(2): 608-16; ISSN: 0022-3565.

UNITED-STATES. We have shown previously that intrathecal

(i.t.) administration of the combination of delta 9-

tetrahydrocannabinol (THC) and morphine results in a greater

than additive antinociceptive effect. Similarly, pretreating

mice with subthreshold doses of the kappa agonist, Dynorphin

A (1-8), produced a parallel, leftward shift of the morphine

dose-response curve, shifting the ED50 of morphine from 0.32

to 0.04 micrograms/mouse. A cocktail of enzyme inhibitors

used to prevent the metabolism of Dynorphin A (1-8) into the

delta receptor agonist, [Leu5]-enkephalin, attenuated the

enhancement of morphine-induced antinociception by delta 9-

THC. The enhanced antinociceptive effect observed after i.t.

administration of the combination of delta 9-THC and

morphine was also attenuated with antisera to Dynorphin A (1-

8) (10 micrograms/ mouse) and Dynorphin A (1-13) (10

micrograms/mouse). Antisera to Dynorphin A (1-8) and

Dynorphin A (1-17) blocked the antinociceptive effects of

delta 9-THC (50 micrograms i.t.) without producing any

significant alteration in the hypothermic and cataleptic

effects or hypomotility produced by delta 9-THC. The

antinociception produced by the combination of delta 9-THC

and morphine was blocked by the kappa antagonist, nor-

binaltorphimine (2 micrograms/ mouse), as well as the delta

antagonist, naltrindole (5 micrograms/ mouse). Thus, the

antinociception of morphine, which is mediated predominately

by mu receptors, may be enhanced by delta 9-THC through the

activation of kappa and delta receptors.. 0; 0; 0; 1972-08-3;

57-27-2; 7440-70-2; 74913-18-1.

380. Pugh, G. Jr; Smith, P. B.; Dombrowski, D. S.; Welch, S. P. The role of

endogenous opioids in enhancing the antinociception produced

by the combination of delta 9-tetrahydrocannabinol and

morphine in the spinal cord. J-Pharmacol-Exp-Ther. 1996 Nov;

279(2): 608-16; ISSN: 0022-3565.

UNITED-STATES. We have shown previously that intrathecal

(i.t.) administration of the combination of delta 9-

tetrahydrocannabinol (THC) and morphine results in a greater

than additive antinociceptive effect. Similarly, pretreating

mice with subthreshold doses of the kappa agonist, Dynorphin

A (1-8), produced a parallel, leftward shift of the morphine

dose-response curve, shifting the ED50 of morphine from 0.32

to 0.04 micrograms/mouse. A cocktail of enzyme inhibitors

used to prevent the metabolism of Dynorphin A (1-8) into the

delta receptor agonist, [Leu5]-enkephalin, attenuated the

enhancement of morphine-induced antinociception by delta 9-

THC. The enhanced antinociceptive effect observed after i.t.

administration of the combination of delta 9-THC and

morphine was also attenuated with antisera to Dynorphin A (1-

8) (10 micrograms/ mouse) and Dynorphin A (1-13) (10

micrograms/mouse). Antisera to Dynorphin A (1-8) and

Dynorphin A (1-17) blocked the antinociceptive effects of

delta 9-THC (50 micrograms i.t.) without producing any

significant alteration in the hypothermic and cataleptic

effects or hypomotility produced by delta 9-THC. The

antinociception produced by the combination of delta 9-THC

and morphine was blocked by the kappa antagonist, nor-

binaltorphimine (2 micrograms/ mouse), as well as the delta

antagonist, naltrindole (5 micrograms/ mouse). Thus, the

antinociception of morphine, which is mediated predominately

by mu receptors, may be enhanced by delta 9-THC through the

activation of kappa and delta receptors.. 0; 0; 0; 1972-08-3;

57-27-2; 7440-70-2; 74913-18-1.

381. Puschel, A. W.; Adams, R. H.; Betz, H. The sensory innervation of

the mouse spinal cord may be patterned by differential

expression of and differential responsiveness to semaphorins.

Mol-Cell-Neurosci. 1996 May; 7(5): 419-31; ISSN: 1044-7431.

UNITED-STATES. To better understand the regulatory

processes underlying axonal pathfinding we analyzed the

embryonic expression of seven murine semaphorin genes by in

situ hybridization In the spinal cord, transcripts of all seven

semaphorin genes were detected from Embryonic Day 11.5

(E11.5) onward and restricted to distinct regions at E15.5.

Interestingly, semE, F, and G mRNAs were in addition

differentially expressed in the ventricular zone of the

telencephalon. In order to correlate these expression patterns

to the behavior of different types of sensory afferents, we

tested their response to recombinant semaphorin proteins.

Specific subpopulations of dorsal root ganglion sensory

neurons displayed a developmentally regulated differential

response to Sem D. Whereas extension of both NGF- and NT-3-

dependent neurites was inhibited by Sem D at E12.5, only

neurites formed in the presence of NGF responded at E14.5.

This suggests that Sem D may be involved in preventing an

early penetration of the spinal cord by sensory afferents and

subsequently shaping their lamina-specific termination.. 0; 0;

0; 0; 0.

382. Puschel, A. W.; Adams, R. H.; Betz, H. The sensory innervation of

the mouse spinal cord may be patterned by differential

expression of and differential responsiveness to semaphorins.

Mol-Cell-Neurosci. 1996 May; 7(5): 419-31; ISSN: 1044-7431.

UNITED-STATES. To better understand the regulatory

processes underlying axonal pathfinding we analyzed the

embryonic expression of seven murine semaphorin genes by in

situ hybridization In the spinal cord, transcripts of all seven

semaphorin genes were detected from Embryonic Day 11.5

(E11.5) onward and restricted to distinct regions at E15.5.

Interestingly, semE, F, and G mRNAs were in addition

differentially expressed in the ventricular zone of the

telencephalon. In order to correlate these expression patterns

to the behavior of different types of sensory afferents, we

tested their response to recombinant semaphorin proteins.

Specific subpopulations of dorsal root ganglion sensory

neurons displayed a developmentally regulated differential

response to Sem D. Whereas extension of both NGF- and NT-3-

dependent neurites was inhibited by Sem D at E12.5, only

neurites formed in the presence of NGF responded at E14.5.

This suggests that Sem D may be involved in preventing an

early penetration of the spinal cord by sensory afferents and

subsequently shaping their lamina-specific termination.. 0; 0;

0; 0; 0.

383. Quencer, R. M.; Bunge, R. P. The injured spinal cord: imaging,

histopathologic clinical correlates, and basic science

approaches to enhancing neural function after spinal cord

injury. Spine. 1996 Sep 15; 21(18): 2064-6; ISSN: 0362-2436.

UNITED-STATES.

384. Quencer, R. M.; Bunge, R. P. The injured spinal cord: imaging,

histopathologic clinical correlates, and basic science

approaches to enhancing neural function after spinal cord

injury. Spine. 1996 Sep 15; 21(18): 2064-6; ISSN: 0362-2436.

UNITED-STATES.

385. Raastad, M.; Johnson, B. R.; Kiehn, O. The number of postsynaptic

currents necessary to produce locomotor-related cyclic

information in neurons in the neonatal rat spinal cord. Neuron.

1996 Oct; 17(4): 729-38; ISSN: 0896-6273.

UNITED-STATES. To understand better how synaptic signaling

contributes to network activity, we analyzed the potential

contribution of putative unitary postsynaptic currents (PSCs)

to locomotor-related information received by spinal

interneurons in neonatal rats. The average cyclic modulation of

the whole-cell current in 13 neurons was quantified as the

difference between the current integral (charge) during the

first and second halves of the cyclic locomotor network

output. Between 7.6 and 303 average unitary PSCs per second

were needed to produce the cyclic modulation. This number is

so low that very few (1-5) of the synapses contributing to the

cyclic information need to be active simultaneously. This

suggests that individual presynaptic cells in a central

locomotor network can have a powerful influence on other

neurons.. 50-67-9; 6384-92-5.

386. Raastad, M.; Johnson, B. R.; Kiehn, O. The number of postsynaptic

currents necessary to produce locomotor-related cyclic

information in neurons in the neonatal rat spinal cord. Neuron.

1996 Oct; 17(4): 729-38; ISSN: 0896-6273.

UNITED-STATES. To understand better how synaptic signaling

contributes to network activity, we analyzed the potential

contribution of putative unitary postsynaptic currents (PSCs)

to locomotor-related information received by spinal

interneurons in neonatal rats. The average cyclic modulation of

the whole-cell current in 13 neurons was quantified as the

difference between the current integral (charge) during the

first and second halves of the cyclic locomotor network

output. Between 7.6 and 303 average unitary PSCs per second

were needed to produce the cyclic modulation. This number is

so low that very few (1-5) of the synapses contributing to the

cyclic information need to be active simultaneously. This

suggests that individual presynaptic cells in a central

locomotor network can have a powerful influence on other

neurons.. 50-67-9; 6384-92-5.

387. Ralston, HJ 3rd; Ohara, P. T.; Meng, X. W.; Wells, J.; Ralston, D. D.

Transneuronal changes of the inhibitory circuitry in the

macaque somatosensory thalamus following lesions of the

dorsal column nuclei. J-Comp-Neurol. 1996 Jul 22; 371(2):

325-35; ISSN: 0021-9967.

UNITED-STATES. The inhibitory circuitry of the

ventroposterolateral nucleus (VPL) of the macaque

somatosensory thalamus was analyzed in normal animals and

in those surviving for a few days or several weeks following a

unilateral lesion of the cuneate nucleus, the source of medial

lemniscal (ML) axons carrying information from the

contralateral upper extremity. Inhibitory synaptic terminals in

the VPL were defined as those that contain flattened or

pleomorphic synaptic vesicles and that can be shown to be

immunoreactive for gamma-aminobutyric acid (GABA). There

are two types of these profiles: F axon terminals that arise

from neurons of the thalamic reticular nucleus, and perhaps

from VPL local circuit neurons (LCNs); and the dendritic

appendages of LCNs that form presynaptic dendrites (PSDs). ML

terminals normally have extensive synaptic interactions with

PSDs but not with F axon terminals. Electron microscopic

analyses revealed that cuneatus lesions resulted in a rapid

loss of ML terminals and a statistically significant reduction

in both F and PSD synaptic profiles. Confocal scanning

microscopy also demonstrated a profound loss of GABA

immunoreactivity in the deafferented VPL. These changes

persisted for more than 20 weeks, without any evidence of

reactive synaptogenesis of surviving sensory afferents or of

inhibitory synapses. The changes in GABA circuitry are

transneuronal, and the possible mechanisms that may underlie

them are discussed. It is suggested that the altered GABAergic

circuitry of the VPL in the monkey may serve as a model for

understanding changes in somatic sensation in the human

following peripheral or central deafferentation.. 56-12-2.

388. Ralston, HJ 3rd; Ohara, P. T.; Meng, X. W.; Wells, J.; Ralston, D. D.

Transneuronal changes of the inhibitory circuitry in the

macaque somatosensory thalamus following lesions of the

dorsal column nuclei. J-Comp-Neurol. 1996 Jul 22; 371(2):

325-35; ISSN: 0021-9967.

UNITED-STATES. The inhibitory circuitry of the

ventroposterolateral nucleus (VPL) of the macaque

somatosensory thalamus was analyzed in normal animals and

in those surviving for a few days or several weeks following a

unilateral lesion of the cuneate nucleus, the source of medial

lemniscal (ML) axons carrying information from the

contralateral upper extremity. Inhibitory synaptic terminals in

the VPL were defined as those that contain flattened or

pleomorphic synaptic vesicles and that can be shown to be

immunoreactive for gamma-aminobutyric acid (GABA). There

are two types of these profiles: F axon terminals that arise

from neurons of the thalamic reticular nucleus, and perhaps

from VPL local circuit neurons (LCNs); and the dendritic

appendages of LCNs that form presynaptic dendrites (PSDs). ML

terminals normally have extensive synaptic interactions with

PSDs but not with F axon terminals. Electron microscopic

analyses revealed that cuneatus lesions resulted in a rapid

loss of ML terminals and a statistically significant reduction

in both F and PSD synaptic profiles. Confocal scanning

microscopy also demonstrated a profound loss of GABA

immunoreactivity in the deafferented VPL. These changes

persisted for more than 20 weeks, without any evidence of

reactive synaptogenesis of surviving sensory afferents or of

inhibitory synapses. The changes in GABA circuitry are

transneuronal, and the possible mechanisms that may underlie

them are discussed. It is suggested that the altered GABAergic

circuitry of the VPL in the monkey may serve as a model for

understanding changes in somatic sensation in the human

following peripheral or central deafferentation.. 56-12-2.

389. Ransom, C. B.; Sontheimer, H.; Janigro, D. Astrocytic inwardly

rectifying potassium currents are dependent on external

sodium ions. J-Neurophysiol. 1996 Jul; 76(1): 626-30; ISSN:

0022-3077.

UNITED-STATES. 1. Two subtypes of astrocytes that expressed

distinctly different ion channel complements were identified

in primary cultures from rat spinal cord and hippocampus

using whole cell patch-clamp techniques. One population of

cells expressed voltage-activated Na+ currents and displayed

outwardly rectifying I-V relationships; the other group of

cells had no detectable Na+ currents and pronounced inwardly

rectifying I-V curves. 2. Astrocytes expressing Na+ currents

were hyperpolarized (by approximately 7 mV) upon removal of

external sodium, suggesting a resting Na+ conductance in these

cells. In contrast, cells expressing primarily inwardly

rectifying K+ currents, Kir, depolarized (by approximately 4-6

mV) in low-sodium solutions. 3. Removal of external Na+ ions

increased the input resistance (189% of control) and reduced

the whole cell current amplitude (60% of control at -120 mV)

of cells with Kir. The reduction in current amplitude was

dose-dependent and became apparent after a 10% reduction of

[Na+]0 in 7/7 cells tested. At -120 mV, the effect was near

maximal in response to a 50% reduction of [Na+]0. 4. The

outward potassium currents of cells expressing Na(+)-currents

were unaffected by removal of bath Na+. 5. We conclude that

the conductance of glial inwardly rectifying K+ channels is

dependent on external sodium ions via a mechanism that does

not involve sodium ion permeation or blockade of these

channels.. 0; 7440-23-5.

390. Ransom, C. B.; Sontheimer, H.; Janigro, D. Astrocytic inwardly

rectifying potassium currents are dependent on external

sodium ions. J-Neurophysiol. 1996 Jul; 76(1): 626-30; ISSN:

0022-3077.

UNITED-STATES. 1. Two subtypes of astrocytes that expressed

distinctly different ion channel complements were identified

in primary cultures from rat spinal cord and hippocampus

using whole cell patch-clamp techniques. One population of

cells expressed voltage-activated Na+ currents and displayed

outwardly rectifying I-V relationships; the other group of

cells had no detectable Na+ currents and pronounced inwardly

rectifying I-V curves. 2. Astrocytes expressing Na+ currents

were hyperpolarized (by approximately 7 mV) upon removal of

external sodium, suggesting a resting Na+ conductance in these

cells. In contrast, cells expressing primarily inwardly

rectifying K+ currents, Kir, depolarized (by approximately 4-6

mV) in low-sodium solutions. 3. Removal of external Na+ ions

increased the input resistance (189% of control) and reduced

the whole cell current amplitude (60% of control at -120 mV)

of cells with Kir. The reduction in current amplitude was

dose-dependent and became apparent after a 10% reduction of

[Na+]0 in 7/7 cells tested. At -120 mV, the effect was near

maximal in response to a 50% reduction of [Na+]0. 4. The

outward potassium currents of cells expressing Na(+)-currents

were unaffected by removal of bath Na+. 5. We conclude that

the conductance of glial inwardly rectifying K+ channels is

dependent on external sodium ions via a mechanism that does

not involve sodium ion permeation or blockade of these

channels.. 0; 7440-23-5.

391. Reinoso, M. A.; Sieck, G. C.; Hubmayr, R. D. Respiratory muscle

coordination in acute spinal dogs. Respir-Physiol. 1996 Apr;

104(1): 29-37; ISSN: 0034-5687.

NETHERLANDS. Our objectives were (1) to test whether

respiratory muscles of spinal dogs can generate the

alternating pattern of activation seen in intact animals and (2)

to characterize the responsiveness of spinal rhythms to

mechanical ventilation. We recorded the electromyographic

activities of inspiratory muscles (diaphragm and parasternal

intercostals) and expiratory muscles (triangularis sterni and

transversus abdominis) in ten anesthetized dogs before and

after transection of the cervical cord at levels C1-C2 (n = 2),

C2-C3 (n = 6), and C8 (n = 2). In 9/10 dogs, we observed short

lasting (3-4 min) rhythmic ventilatory muscle activity for up

to 3 h after transection. Inspiratory and expiratory muscles

contracted simultaneously, suggesting an absence of

mechanism(s) responsible for reciprocal muscle activation on

a spinal level. Five of ten dogs showed tonic rib cage activity

during apnea that was phasically modulated during mechanical

ventilation. From the absence of alternating inspiratory and

expiratory muscle activity in acute spinalized dogs, we

conclude that dogs do not have a spinal pattern generator for

respiration.

392. Reinoso, M. A.; Sieck, G. C.; Hubmayr, R. D. Respiratory muscle

coordination in acute spinal dogs. Respir-Physiol. 1996 Apr;

104(1): 29-37; ISSN: 0034-5687.

NETHERLANDS. Our objectives were (1) to test whether

respiratory muscles of spinal dogs can generate the

alternating pattern of activation seen in intact animals and (2)

to characterize the responsiveness of spinal rhythms to

mechanical ventilation. We recorded the electromyographic

activities of inspiratory muscles (diaphragm and parasternal

intercostals) and expiratory muscles (triangularis sterni and

transversus abdominis) in ten anesthetized dogs before and

after transection of the cervical cord at levels C1-C2 (n = 2),

C2-C3 (n = 6), and C8 (n = 2). In 9/10 dogs, we observed short

lasting (3-4 min) rhythmic ventilatory muscle activity for up

to 3 h after transection. Inspiratory and expiratory muscles

contracted simultaneously, suggesting an absence of

mechanism(s) responsible for reciprocal muscle activation on

a spinal level. Five of ten dogs showed tonic rib cage activity

during apnea that was phasically modulated during mechanical

ventilation. From the absence of alternating inspiratory and

expiratory muscle activity in acute spinalized dogs, we

conclude that dogs do not have a spinal pattern generator for

respiration.

393. Rosenberg, L. J.; Jordan, R. S.; Gross, G. W.; Emery, D. G.; Lucas, J.

H. Effects of methylprednisolone on lesioned and uninjured

mammalian spinal neurons: viability, ultrastructure, and

network electrophysiology. J-Neurotrauma. 1996 Aug; 13(8):

417-37; ISSN: 0897-7151.

UNITED-STATES. An in vitro investigation was undertaken to

provide information regarding the effectiveness of

methylprednisolone sodium succinate (MPSS) as a treatment

for the primary mechanical injury of spinal cord (SC) trauma.

Exposure of uninjured mouse SC cells to MPSS for 24 h caused

neuronal stress when the concentration exceeded 150

micrograms/mL; neuronal death occurred at concentrations

above 600 micrograms/mL. The concentration range for MPSS

protection of SC neurons subjected to a defined physical injury

(laser microbeam transection of a primary dendrite 100

microns from the perikaryon) was very narrow: survival in the

30 micrograms/mL group differed significantly from the

untreated control group (68.5% +/- 14.1 vs. 47.1% +/- 14.1),

treatment with 20 or 60 micrograms/mL MPSS did not

increase survival, and treatment with 100 micrograms/mL

MPSS accelerated ultrastructural deterioration and increased

the likelihood of death. Enhanced survival of lesioned neurons

was observed when 30 micrograms/mL MPSS was applied

within 15 min of dendrotomy but not when MPSS was

administered 2 h after lesioning. Multimicroelectrode plate

(MMEP) studies of SC network electrical activity indicated

that MPSS associated readily with neuronal membranes. This

finding was consistent with the hypothesis that MPSS may

protect lesioned neurons by stabilizing damaged membranes,

enhancing lesion resealing, and limiting the spread of ion-

mediated damage. However, comparisons of neurite die-back

24 h after dendrotomy found no significant difference between

MPSS-treated and control neurons. Application of 30 or 100

micrograms/mL MPSS increased the spontaneous burst activity

of SC networks grown on MMEPs, however, there was no

evidence that the increased excitability at these

concentrations was the result of specific actions of MPSS on

GABA or NMDA synapses.. 2921-57-5.

394. Rosenberg, L. J.; Jordan, R. S.; Gross, G. W.; Emery, D. G.; Lucas, J.

H. Effects of methylprednisolone on lesioned and uninjured

mammalian spinal neurons: viability, ultrastructure, and

network electrophysiology. J-Neurotrauma. 1996 Aug; 13(8):

417-37; ISSN: 0897-7151.

UNITED-STATES. An in vitro investigation was undertaken to

provide information regarding the effectiveness of

methylprednisolone sodium succinate (MPSS) as a treatment

for the primary mechanical injury of spinal cord (SC) trauma.

Exposure of uninjured mouse SC cells to MPSS for 24 h caused

neuronal stress when the concentration exceeded 150

micrograms/mL; neuronal death occurred at concentrations

above 600 micrograms/mL. The concentration range for MPSS

protection of SC neurons subjected to a defined physical injury

(laser microbeam transection of a primary dendrite 100

microns from the perikaryon) was very narrow: survival in the

30 micrograms/mL group differed significantly from the

untreated control group (68.5% +/- 14.1 vs. 47.1% +/- 14.1),

treatment with 20 or 60 micrograms/mL MPSS did not

increase survival, and treatment with 100 micrograms/mL

MPSS accelerated ultrastructural deterioration and increased

the likelihood of death. Enhanced survival of lesioned neurons

was observed when 30 micrograms/mL MPSS was applied

within 15 min of dendrotomy but not when MPSS was

administered 2 h after lesioning. Multimicroelectrode plate

(MMEP) studies of SC network electrical activity indicated

that MPSS associated readily with neuronal membranes. This

finding was consistent with the hypothesis that MPSS may

protect lesioned neurons by stabilizing damaged membranes,

enhancing lesion resealing, and limiting the spread of ion-

mediated damage. However, comparisons of neurite die-back

24 h after dendrotomy found no significant difference between

MPSS-treated and control neurons. Application of 30 or 100

micrograms/mL MPSS increased the spontaneous burst activity

of SC networks grown on MMEPs, however, there was no

evidence that the increased excitability at these

concentrations was the result of specific actions of MPSS on

GABA or NMDA synapses.. 2921-57-5.

395. Rosin, D. L.; Talley, E. M.; Lee, A.; Stornetta, R. L.; Gaylinn, B. D.;

Guyenet, P. G.; Lynch, K. R. Distribution of alpha 2C-adrenergic

receptor-like immunoreactivity in the rat central nervous

system. J-Comp-Neurol. 1996 Aug 12; 372(1): 135-65; ISSN:

0021-9967.

UNITED-STATES. The distribution of alpha 2C-adrenergic

receptors (ARs) in rat brain and spinal cord was examined

immunohistochemically by using an affinity purified

polyclonal antibody. The antibody was directed against a

recombinant fusion protein consisting of a 70-amino-acid

polypeptide portion of the third intracellular loop of the alpha

2C-AR fused to glutathione-S-transferase. Selectivity and

subtype specificity of the antibody were demonstrated by

immunoprecipitation of [125I]-photoaffinity-labeled alpha 2-

AR and by immunohistochemical labeling of COS cells

expressing the individual rat alpha 2-AR subtypes. In both

cases the antibody recognized only the alpha 2C-AR subtype,

and immunoreactivity was eliminated by preadsorption of the

antibody with excess antigen. In rat brain, alpha 2C-AR-like

immunoreactivity (alpha 2C-AR-LI) was found primarily in

neuronal perikarya, with some labeling of proximal dendrites;

analysis by confocal microscopy revealed the intracellular

localization of some of the immunoreactivity. Areas of dense

immunoreactivity include anterior olfactory nucleus, piriform

cortex, septum, diagonal band, pallidum, preoptic areas,

supraoptic nucleus, suprachiasmatic nucleus, paraventricular

nucleus, amygdala, hippocampus (CA1 and dentate gyrus),

substantia nigra, ventral tegmental area, raphe (pontine and

medullary), motor trigeminal nucleus, facial nucleus,

vestibular nucleus, dorsal motor nucleus of the vagus, and

hypoglossal nucleus. Labeling was found in specific laminae

throughout the cortex, and a sparse distribution of very darkly

labeled cells was observed in the striatum. At all levels of the

spinal cord there were small numbers of large, darkly labeled

cells in layer IX and much smaller cells in layer X. In general,

the pattern of alpha 2C-LI throughout the neuraxis is

consistent with previously published reports of the

distribution of receptor mRNA detected by hybridization

histochemistry.. 0.

396. Rosin, D. L.; Talley, E. M.; Lee, A.; Stornetta, R. L.; Gaylinn, B. D.;

Guyenet, P. G.; Lynch, K. R. Distribution of alpha 2C-adrenergic

receptor-like immunoreactivity in the rat central nervous

system. J-Comp-Neurol. 1996 Aug 12; 372(1): 135-65; ISSN:

0021-9967.

UNITED-STATES. The distribution of alpha 2C-adrenergic

receptors (ARs) in rat brain and spinal cord was examined

immunohistochemically by using an affinity purified

polyclonal antibody. The antibody was directed against a

recombinant fusion protein consisting of a 70-amino-acid

polypeptide portion of the third intracellular loop of the alpha

2C-AR fused to glutathione-S-transferase. Selectivity and

subtype specificity of the antibody were demonstrated by

immunoprecipitation of [125I]-photoaffinity-labeled alpha 2-

AR and by immunohistochemical labeling of COS cells

expressing the individual rat alpha 2-AR subtypes. In both

cases the antibody recognized only the alpha 2C-AR subtype,

and immunoreactivity was eliminated by preadsorption of the

antibody with excess antigen. In rat brain, alpha 2C-AR-like

immunoreactivity (alpha 2C-AR-LI) was found primarily in

neuronal perikarya, with some labeling of proximal dendrites;

analysis by confocal microscopy revealed the intracellular

localization of some of the immunoreactivity. Areas of dense

immunoreactivity include anterior olfactory nucleus, piriform

cortex, septum, diagonal band, pallidum, preoptic areas,

supraoptic nucleus, suprachiasmatic nucleus, paraventricular

nucleus, amygdala, hippocampus (CA1 and dentate gyrus),

substantia nigra, ventral tegmental area, raphe (pontine and

medullary), motor trigeminal nucleus, facial nucleus,

vestibular nucleus, dorsal motor nucleus of the vagus, and

hypoglossal nucleus. Labeling was found in specific laminae

throughout the cortex, and a sparse distribution of very darkly

labeled cells was observed in the striatum. At all levels of the

spinal cord there were small numbers of large, darkly labeled

cells in layer IX and much smaller cells in layer X. In general,

the pattern of alpha 2C-LI throughout the neuraxis is

consistent with previously published reports of the

distribution of receptor mRNA detected by hybridization

histochemistry.. 0.

397. Roychowdhury, S. M.; Fields, H. L. Endogenous opioids acting at a

medullary mu-opioid receptor contribute to the behavioral

antinociception produced by GABA antagonism in the midbrain

periaqueductal gray. Neuroscience. 1996 Oct; 74(3): 863-72;

ISSN: 0306-4522.

UNITED-STATES. This study examined the contribution of

endogenous opioids to the antinociception produced by

microinjection of the GABAA receptor antagonist, bicuculline,

into the rat midbrain ventrolateral periaqueductal gray region.

Microinjection of bicuculline (40 ng/0.4 microliter) into the

periaqueductal gray produced robust antinociception as

measured by the tail-flick latency to noxious heat. This

antinociception was partially reversed by intravenous

administration of the non-selective opioid antagonist naloxone

hydrochloride (1 and 5 mg/kg), indicating that endogenous

opioid release is necessary for this effect. To determine

whether opioid release in the rostral ventromedial medulla, a

major projection target of the periaqueductal gray,

contributes to this effect, we microinjected another opioid

antagonist, naltrexone, into the rostral ventromedial medulla.

Naltrexone in the rostral ventromedial medulla (5 and 10

micrograms/microliter) significantly attenuated bicuculline

antinociception elicited from the periaqueductal gray. Cys2,

tyr3, orn5, pen7-amide (26.5 nmol), a selective mu-opioid

receptor antagonist, also reversed the antinociception when

microinjected into the rostral ventromedial medulla.

Microinjections of naltrexone (10 micrograms/microliter) or

cys2, tyr3, orn5, pen7-amide at sites in the medulla dorsal to

the rostral ventromedial medulla were ineffective. None of the

antagonists altered baseline tail-flick latencies. These

results support the hypothesis that a population of

periaqueductal gray neurons produces antinociception through

a mu-opioid receptor-mediated action of endogenous opioids in

the rostral ventromedial medulla. Thus, two opioid-sensitive

pain-modulating brainstem sites are linked by an endogenous

opioid synapse in the rostral ventromedial medulla.. 0; 0; 0;

103429-31-8; 16590-41-3; 465-65-6; 485-49-4; 51110-01-

1.

398. Roychowdhury, S. M.; Fields, H. L. Endogenous opioids acting at a

medullary mu-opioid receptor contribute to the behavioral

antinociception produced by GABA antagonism in the midbrain

periaqueductal gray. Neuroscience. 1996 Oct; 74(3): 863-72;

ISSN: 0306-4522.

UNITED-STATES. This study examined the contribution of

endogenous opioids to the antinociception produced by

microinjection of the GABAA receptor antagonist, bicuculline,

into the rat midbrain ventrolateral periaqueductal gray region.

Microinjection of bicuculline (40 ng/0.4 microliter) into the

periaqueductal gray produced robust antinociception as

measured by the tail-flick latency to noxious heat. This

antinociception was partially reversed by intravenous

administration of the non-selective opioid antagonist naloxone

hydrochloride (1 and 5 mg/kg), indicating that endogenous

opioid release is necessary for this effect. To determine

whether opioid release in the rostral ventromedial medulla, a

major projection target of the periaqueductal gray,

contributes to this effect, we microinjected another opioid

antagonist, naltrexone, into the rostral ventromedial medulla.

Naltrexone in the rostral ventromedial medulla (5 and 10

micrograms/microliter) significantly attenuated bicuculline

antinociception elicited from the periaqueductal gray. Cys2,

tyr3, orn5, pen7-amide (26.5 nmol), a selective mu-opioid

receptor antagonist, also reversed the antinociception when

microinjected into the rostral ventromedial medulla.

Microinjections of naltrexone (10 micrograms/microliter) or

cys2, tyr3, orn5, pen7-amide at sites in the medulla dorsal to

the rostral ventromedial medulla were ineffective. None of the

antagonists altered baseline tail-flick latencies. These

results support the hypothesis that a population of

periaqueductal gray neurons produces antinociception through

a mu-opioid receptor-mediated action of endogenous opioids in

the rostral ventromedial medulla. Thus, two opioid-sensitive

pain-modulating brainstem sites are linked by an endogenous

opioid synapse in the rostral ventromedial medulla.. 0; 0; 0;

103429-31-8; 16590-41-3; 465-65-6; 485-49-4; 51110-01-

1.

399. Rutberg, M.; Modig, C.; Wallin, M. Detyrosination of tubulin is not

correlated to cold-adaptation of microtubules in cultured cells

from the Atlantic cod (Gadus morhua). Histochem-J. 1996 Jul;

28(7): 511-21; ISSN: 0018-2214.

ENGLAND. Isolated cod brain microtubules from the cold-

adapted Atlantic cod (Gadus morhua) have previously been

shown to be highly detyrosinated, a post-translational

modification of tubulin usually found in stable subsets of

microtubules. In this study we found this was not restricted

only to isolated brain microtubules. Microtubules in primary

cultures of brain and skin cells were composed of both

tyrosinated (Tyr)- and detyrosinated (Glu)-tubulin seen by

immunocytochemistry. Immunoelectron microscopy of isolated

microtubules showed that individual microtubules were

composed of a mixture of Tyr- and Glu-tubulin. Leukocytes

with extending lamellopodia contained only microtubules

stained with the antibody against Tyr-tubulin, and isolated

heart tubulin lacked both Tyr- and Glu-tubulin, suggesting that

a relative high level of detyrosination is a characteristic of

most, but not all, cod microtubules. Brain cell microtubules

were more resistant to mitotic inhibitors than skin cell

microtubules, but this was not correlated to a difference in

detyrosination. Brain and skin cell microtubules were only

partially disassembled when incubated at 0 degrees C. Upon

reassembly of microtubules at 12 degrees C, microtubules

were still made of mixtures of Tyr- and Glu-tubulin,

indicating that detyrosination of assembled microtubules is

rapid and/or that in cod cells in contrast to mammalian cells,

Glu-tubulin can reassemble to microtubules. Our data show

that most cod microtubules are highly detyrosinated, but this

is not the cause of their cold adaptation or drug stability.. 0.

400. Rutberg, M.; Modig, C.; Wallin, M. Detyrosination of tubulin is not

correlated to cold-adaptation of microtubules in cultured cells

from the Atlantic cod (Gadus morhua). Histochem-J. 1996 Jul;

28(7): 511-21; ISSN: 0018-2214.

ENGLAND. Isolated cod brain microtubules from the cold-

adapted Atlantic cod (Gadus morhua) have previously been

shown to be highly detyrosinated, a post-translational

modification of tubulin usually found in stable subsets of

microtubules. In this study we found this was not restricted

only to isolated brain microtubules. Microtubules in primary

cultures of brain and skin cells were composed of both

tyrosinated (Tyr)- and detyrosinated (Glu)-tubulin seen by

immunocytochemistry. Immunoelectron microscopy of isolated

microtubules showed that individual microtubules were

composed of a mixture of Tyr- and Glu-tubulin. Leukocytes

with extending lamellopodia contained only microtubules

stained with the antibody against Tyr-tubulin, and isolated

heart tubulin lacked both Tyr- and Glu-tubulin, suggesting that

a relative high level of detyrosination is a characteristic of

most, but not all, cod microtubules. Brain cell microtubules

were more resistant to mitotic inhibitors than skin cell

microtubules, but this was not correlated to a difference in

detyrosination. Brain and skin cell microtubules were only

partially disassembled when incubated at 0 degrees C. Upon

reassembly of microtubules at 12 degrees C, microtubules

were still made of mixtures of Tyr- and Glu-tubulin,

indicating that detyrosination of assembled microtubules is

rapid and/or that in cod cells in contrast to mammalian cells,

Glu-tubulin can reassemble to microtubules. Our data show

that most cod microtubules are highly detyrosinated, but this

is not the cause of their cold adaptation or drug stability.. 0.

401. Safi, H. J. Role of the BioMedicus pump and distal aortic perfusion

in thoracoabdominal aortic aneurysm repair. Artif-Organs.

1996 Jun; 20(6): 694-9; ISSN: 0160-564X.

UNITED-STATES. We reviewed the role of the BioMedicus pump

in the reduction of neurologic complications following the

repair of Type 1 and Type 2 thoracoabdominal aortic

aneurysms. Since 1991, we have used several different

methods for the repair of thoracoabdominal aortic aneurysms

including simple cross-clamping, selective use of the

BioMedicus pump, cardiopulmonary bypass with or without

profound hypothermia, and most recently, distal aortic

perfusion using the BioMedicus pump combined with cerebral

spinal fluid drainage. This latter method has been the most

promising in rectifying the side effects of aortic clamping and

in providing the time necessary for thorough thoracoabdominal

aortic aneurysm repair. On our service, the ongoing study of

the BioMedicus pump and distal aortic perfusion in conjunction

with cerebral spinal fluid drainage has shown that these

adjuncts can extend the tolerance of the spinal cord to

ischemia and lower the overall rate of neurologic

complications for Type 1 and Type 2 thoracoabdominal aortic

aneurysm repairs to a rate of 5% (early results) and 3% (late

results). We highly recommend distal aortic perfusion using

the BioMedicus pump combined with cerebral spinal fluid

drainage for thoracoabdominal aortic aneurysm repair.

402. Safi, H. J. Role of the BioMedicus pump and distal aortic perfusion

in thoracoabdominal aortic aneurysm repair. Artif-Organs.

1996 Jun; 20(6): 694-9; ISSN: 0160-564X.

UNITED-STATES. We reviewed the role of the BioMedicus pump

in the reduction of neurologic complications following the

repair of Type 1 and Type 2 thoracoabdominal aortic

aneurysms. Since 1991, we have used several different

methods for the repair of thoracoabdominal aortic aneurysms

including simple cross-clamping, selective use of the

BioMedicus pump, cardiopulmonary bypass with or without

profound hypothermia, and most recently, distal aortic

perfusion using the BioMedicus pump combined with cerebral

spinal fluid drainage. This latter method has been the most

promising in rectifying the side effects of aortic clamping and

in providing the time necessary for thorough thoracoabdominal

aortic aneurysm repair. On our service, the ongoing study of

the BioMedicus pump and distal aortic perfusion in conjunction

with cerebral spinal fluid drainage has shown that these

adjuncts can extend the tolerance of the spinal cord to

ischemia and lower the overall rate of neurologic

complications for Type 1 and Type 2 thoracoabdominal aortic

aneurysm repairs to a rate of 5% (early results) and 3% (late

results). We highly recommend distal aortic perfusion using

the BioMedicus pump combined with cerebral spinal fluid

drainage for thoracoabdominal aortic aneurysm repair.

403. Sakurada, T.; Sugiyama, A.; Sakurada, C.; Tanno, K.; Sakurada, S.;

Kisara, K.; Hara, A.; Abiko, Y. Involvement of nitric oxide in

spinally mediated capsaicin- and glutamate-induced

behavioural responses in the mouse. Neurochem-Int. 1996 Sep;

29(3): 271-8; ISSN: 0197-0186.

ENGLAND. The intrathecal (i.t.) injection of capsaicin (0.1

nmol/mouse) through a lumbar puncture elicited scratching,

biting and licking responses. Pretreatment with the nitric

oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-

NAME) (320 nmol), by i.t. injection, resulted in a significant

inhibition of the behavioural response produced by i.t.

capsaicin (0.1 nmol/mouse). Similar behavioural responses

were induced by i.t. injections of NMDA (0.4 nmol), kainate

(0.05 nmol) or AMPA (0.05 nmol), which were all inhibited by

co-administration of L-NAME (20-80 nmol). L-Arginine (600

mg/kg, i.p.) but not D-arginine (600 mg/kg, i.p.) reversed the

inhibitory effect of L-NAME on capsaicin-, NMDA-, kainate-

and AMPA-induced behavioural response. Scratching, biting and

licking responses induced by tachykinin receptor agonists,

substance P, [Sar9,Met(O2)11]substance P, neurokinin A and

neurokinin B were not affected by co-administration of L-

NAME (40 and 80 nmol). These results suggest that spinal

nitric oxide may play a significant role in mechanisms of the

behavioural response to capsaicin, probably through the

release of glutamate, but not tachykinins.. EC 1.14.13.39; 0; 0;

0; 10102-43-9; 404-86-4; 487-79-6; 50903-99-6; 56-86-0;

6384-92-5; 77521-29-0.

404. Sakurada, T.; Sugiyama, A.; Sakurada, C.; Tanno, K.; Sakurada, S.;

Kisara, K.; Hara, A.; Abiko, Y. Involvement of nitric oxide in

spinally mediated capsaicin- and glutamate-induced

behavioural responses in the mouse. Neurochem-Int. 1996 Sep;

29(3): 271-8; ISSN: 0197-0186.

ENGLAND. The intrathecal (i.t.) injection of capsaicin (0.1

nmol/mouse) through a lumbar puncture elicited scratching,

biting and licking responses. Pretreatment with the nitric

oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-

NAME) (320 nmol), by i.t. injection, resulted in a significant

inhibition of the behavioural response produced by i.t.

capsaicin (0.1 nmol/mouse). Similar behavioural responses

were induced by i.t. injections of NMDA (0.4 nmol), kainate

(0.05 nmol) or AMPA (0.05 nmol), which were all inhibited by

co-administration of L-NAME (20-80 nmol). L-Arginine (600

mg/kg, i.p.) but not D-arginine (600 mg/kg, i.p.) reversed the

inhibitory effect of L-NAME on capsaicin-, NMDA-, kainate-

and AMPA-induced behavioural response. Scratching, biting and

licking responses induced by tachykinin receptor agonists,

substance P, [Sar9,Met(O2)11]substance P, neurokinin A and

neurokinin B were not affected by co-administration of L-

NAME (40 and 80 nmol). These results suggest that spinal

nitric oxide may play a significant role in mechanisms of the

behavioural response to capsaicin, probably through the

release of glutamate, but not tachykinins.. EC 1.14.13.39; 0; 0;

0; 10102-43-9; 404-86-4; 487-79-6; 50903-99-6; 56-86-0;

6384-92-5; 77521-29-0.

405. Sakurada, T.; Wako, K.; Sakurada, C.; Manome, Y.; Tan, no K.;

Sakurada, S.; Kisara, K. Spinally-mediated behavioural

responses evoked by intrathecal high-dose morphine: possible

involvement of substance P in the mouse spinal cord. Brain-

Res. 1996 Jun 17; 724(2): 213-21; ISSN: 0006-8993.

NETHERLANDS. Intrathecal (i.t.) administration of morphine in

the spinal subarachnoid space of mice produced a severe

hindlimb scratching followed by biting and licking. The onset

of the scratching behaviour was observed 60-70 s after i.t.

injection of morphine (60 and 90 nmol), and had a duration of

3-4 min. The morphine-induced behaviour was increased

additively by i.t. co-administration of substance P (SP). This

characteristic behavioural response was inhibited dose-

dependently by i.t. co-administration of the tachykinin NK-1

receptor antagonists, sendide and CP-96,345. Significant

antagonistic effects of SP (1-7), a putative antagonist for NK-

1 receptors and [D-Phe7, D-His9]SP (6-11), a selective

antagonist for SP receptors, were observed against the

morphine-induced behaviour. Pretreatment with i.t. SP

antiserum and i.t. capsaicin resulted in reduction of the

response to morphine. I.t. administration of somatostatin

(SOM) antiserum, cysteamine, a relatively selective depletor

of SOM and cyclo-SOM, a SOM receptor antagonist, produced no

inhibitory effect on the morphine-induced behaviour. These

results demonstrate that a spinal system of neurones

containing SP may be involved in elicitation of the behavioural

episode following i.t. injection of morphine in mice.. 0; 0; 0; 0;

0; 33507-63-0; 404-86-4; 51-85-4; 51110-01-1; 57-27-2.

406. Sakurada, T.; Wako, K.; Sakurada, C.; Manome, Y.; Tan, no K.;

Sakurada, S.; Kisara, K. Spinally-mediated behavioural

responses evoked by intrathecal high-dose morphine: possible

involvement of substance P in the mouse spinal cord. Brain-

Res. 1996 Jun 17; 724(2): 213-21; ISSN: 0006-8993.

NETHERLANDS. Intrathecal (i.t.) administration of morphine in

the spinal subarachnoid space of mice produced a severe

hindlimb scratching followed by biting and licking. The onset

of the scratching behaviour was observed 60-70 s after i.t.

injection of morphine (60 and 90 nmol), and had a duration of

3-4 min. The morphine-induced behaviour was increased

additively by i.t. co-administration of substance P (SP). This

characteristic behavioural response was inhibited dose-

dependently by i.t. co-administration of the tachykinin NK-1

receptor antagonists, sendide and CP-96,345. Significant

antagonistic effects of SP (1-7), a putative antagonist for NK-

1 receptors and [D-Phe7, D-His9]SP (6-11), a selective

antagonist for SP receptors, were observed against the

morphine-induced behaviour. Pretreatment with i.t. SP

antiserum and i.t. capsaicin resulted in reduction of the

response to morphine. I.t. administration of somatostatin

(SOM) antiserum, cysteamine, a relatively selective depletor

of SOM and cyclo-SOM, a SOM receptor antagonist, produced no

inhibitory effect on the morphine-induced behaviour. These

results demonstrate that a spinal system of neurones

containing SP may be involved in elicitation of the behavioural

episode following i.t. injection of morphine in mice.. 0; 0; 0; 0;

0; 33507-63-0; 404-86-4; 51-85-4; 51110-01-1; 57-27-2.

407. Schmidt, C.; Kunemund, V.; Wintergerst, E. S.; Schmitz, B.;

Schachner, M. CD9 of mouse brain is implicated in neurite

outgrowth and cell migration in vitro and is associated with

the alpha 6/beta 1 integrin and the neural adhesion molecule

L1. J-Neurosci-Res. 1996 Jan 1; 43(1): 12-31; ISSN: 0360-

4012.

UNITED-STATES. We describe here a novel monoclonal antibody

(mab H6) which recognizes CD9, an integral cell surface

constituent previously described in cells of the hematopoietic

lineage and involved in the aggregation of platelets. Mab H6

was raised against membranes of immature mouse astrocytes

and reacted with a protein of 25-27 kD in detergent extracts

of adult mouse brain membranes. Sequence analysis of the N-

terminal amino acids revealed an identity of 96% with CD9

from mouse kidney. CD9 was localized in the central and

peripheral mouse nervous systems: in the spinal cord of 11-

day-old mouse embryos, CD9 was strongly expressed in the

floor and roof plates. In the adult mouse sciatic nerve, myelin

sheaths were highly CD9-immunoreactive. Mab H6 reacted with

the cell surfaces of both glial cells and neurons in culture and

inhibited migration of neuronal cell bodies, neurite

fasciculation and outgrowth of astrocytic processes from

cerebellar microexplants. Neurite outgrowth from isolated

small cerebellar neurons was increased in the presence of mab

H6 on substrate-coated laminin, but not on substrate-coated

poly-L-lysine. Addition of mab H6 elicited an increase in

intracellular Ca2+ concentration in these cells on substrate-

coated laminin. Immunoprecipitates of CD9 from cultured

mouse neuroblastoma N2A cells contained the alpha 6/beta 1

integrin. Moreover, preparations of CD9 immunoaffinity-

purified from adult mouse brain using a mab H6 column

contained the neural adhesion molecule L1, but not other

neural adhesion molecules. CD9 bound to L1, but not to NCAM or

MAG. Both the alpha 6/beta 1 integrin and L1 could be induced

to coredistribute with CD9 on the surface of cultured

neuroblastoma N2A cells. The combined observations suggest

that CD9 can associate with L1 and alpha 6/beta 1 integrin to

influence neural cell interactions in vitro.. 0; 0; 0; 0; 0; 0; 0;

0; 0; 147785-22-6; 25104-18-1; 7440-70-2.

408. Schmidt, C.; Kunemund, V.; Wintergerst, E. S.; Schmitz, B.;

Schachner, M. CD9 of mouse brain is implicated in neurite

outgrowth and cell migration in vitro and is associated with

the alpha 6/beta 1 integrin and the neural adhesion molecule

L1. J-Neurosci-Res. 1996 Jan 1; 43(1): 12-31; ISSN: 0360-

4012.

UNITED-STATES. We describe here a novel monoclonal antibody

(mab H6) which recognizes CD9, an integral cell surface

constituent previously described in cells of the hematopoietic

lineage and involved in the aggregation of platelets. Mab H6

was raised against membranes of immature mouse astrocytes

and reacted with a protein of 25-27 kD in detergent extracts

of adult mouse brain membranes. Sequence analysis of the N-

terminal amino acids revealed an identity of 96% with CD9

from mouse kidney. CD9 was localized in the central and

peripheral mouse nervous systems: in the spinal cord of 11-

day-old mouse embryos, CD9 was strongly expressed in the

floor and roof plates. In the adult mouse sciatic nerve, myelin

sheaths were highly CD9-immunoreactive. Mab H6 reacted with

the cell surfaces of both glial cells and neurons in culture and

inhibited migration of neuronal cell bodies, neurite

fasciculation and outgrowth of astrocytic processes from

cerebellar microexplants. Neurite outgrowth from isolated

small cerebellar neurons was increased in the presence of mab

H6 on substrate-coated laminin, but not on substrate-coated

poly-L-lysine. Addition of mab H6 elicited an increase in

intracellular Ca2+ concentration in these cells on substrate-

coated laminin. Immunoprecipitates of CD9 from cultured

mouse neuroblastoma N2A cells contained the alpha 6/beta 1

integrin. Moreover, preparations of CD9 immunoaffinity-

purified from adult mouse brain using a mab H6 column

contained the neural adhesion molecule L1, but not other

neural adhesion molecules. CD9 bound to L1, but not to NCAM or

MAG. Both the alpha 6/beta 1 integrin and L1 could be induced

to coredistribute with CD9 on the surface of cultured

neuroblastoma N2A cells. The combined observations suggest

that CD9 can associate with L1 and alpha 6/beta 1 integrin to

influence neural cell interactions in vitro.. 0; 0; 0; 0; 0; 0; 0;

0; 0; 147785-22-6; 25104-18-1; 7440-70-2.

409. Schotland, J. L.; Shupliakov, O.; Grillner, S.; Brodin, L. Synaptic and

nonsynaptic monoaminergic neuron systems in the lamprey

spinal cord. J-Comp-Neurol. 1996 Aug 19; 372(2): 229-44;

ISSN: 0021-9967.

UNITED-STATES. In the lamprey spinal cord, dopamine- (DA)

and 5-hydroxytryptamine-(5-HT) containing cells appear to

play an important role in controlling the firing properties of

motoneurons and interneurons and, thereby, in modulating the

efferent motor pattern. To determine the detailed morphology

and synaptic connectivity of the intraspinal DA and 5-HT

systems in Lampetra fluviatilis and Ichthyomyzon unicuspis,

DA and 5-HT antisera were used in light and electron

microscopic immunocytochemical experiments. Two main

groups of labeled cells were distinguished: DA-containing

liquor-contacting (LC) cells distributed along the central

canal, and 5-HT+DA-containing multipolar cells located near

the midline ventral to the central canal. Both types were

synaptically connected with other neuronal elements. The DA-

immunoreactive LC cells, which extended a ciliated process

into the central canal, received symmetrical synapses from

unlabeled terminals containing small synaptic vesicles. The

distal process of the LC cells could be traced to the lateral

cell column, to the ventral aspect of the dorsal column, or to

the ventromedial area. Ultrastructural analysis of DA fibers in

these regions showed the presence of labeled terminals

containing numerous small synaptic vesicles and a few dense-

core vesicles. These terminals formed symmetrical synapses

with unlabeled cell bodies and dendrites, with GABA-

immunopositive LC cells, and with the multipolar DA+5-HT

cells. The multipolar DA+5-HT cells also received input from

unlabeled synapses. Intracellular recording from these cells

showed that they received excitatory postsynaptic potentials

in response to stimulation of fibers in the ventromedial tracts

and dorsal roots. The terminals of the multipolar DA+5-HT

neurons in the ventromedial spinal cord contained numerous

dense-core vesicles and small synaptic vesicles, but no

synaptic specializations could be detected. In addition, a small

number of larger DA-immunoreactive cells were observed in

the lateral cell column at rostral levels. The lamprey spinal

cord thus contains distinct populations of synaptically

interconnected monoaminergic neurons. Dopamine-containing

LC cells synapse onto DA+5-HT-containing multipolar cells, in

addition to GABAergic LC cells and unidentified spinal neurons.

In contrast, the multipolar cells appear to exert their

influence by nonsynaptic mechanisms.. 0; 51-61-6; 56-12-2.

410. Schotland, J. L.; Shupliakov, O.; Grillner, S.; Brodin, L. Synaptic and

nonsynaptic monoaminergic neuron systems in the lamprey

spinal cord. J-Comp-Neurol. 1996 Aug 19; 372(2): 229-44;

ISSN: 0021-9967.

UNITED-STATES. In the lamprey spinal cord, dopamine- (DA)

and 5-hydroxytryptamine-(5-HT) containing cells appear to

play an important role in controlling the firing properties of

motoneurons and interneurons and, thereby, in modulating the

efferent motor pattern. To determine the detailed morphology

and synaptic connectivity of the intraspinal DA and 5-HT

systems in Lampetra fluviatilis and Ichthyomyzon unicuspis,

DA and 5-HT antisera were used in light and electron

microscopic immunocytochemical experiments. Two main

groups of labeled cells were distinguished: DA-containing

liquor-contacting (LC) cells distributed along the central

canal, and 5-HT+DA-containing multipolar cells located near

the midline ventral to the central canal. Both types were

synaptically connected with other neuronal elements. The DA-

immunoreactive LC cells, which extended a ciliated process

into the central canal, received symmetrical synapses from

unlabeled terminals containing small synaptic vesicles. The

distal process of the LC cells could be traced to the lateral

cell column, to the ventral aspect of the dorsal column, or to

the ventromedial area. Ultrastructural analysis of DA fibers in

these regions showed the presence of labeled terminals

containing numerous small synaptic vesicles and a few dense-

core vesicles. These terminals formed symmetrical synapses

with unlabeled cell bodies and dendrites, with GABA-

immunopositive LC cells, and with the multipolar DA+5-HT

cells. The multipolar DA+5-HT cells also received input from

unlabeled synapses. Intracellular recording from these cells

showed that they received excitatory postsynaptic potentials

in response to stimulation of fibers in the ventromedial tracts

and dorsal roots. The terminals of the multipolar DA+5-HT

neurons in the ventromedial spinal cord contained numerous

dense-core vesicles and small synaptic vesicles, but no

synaptic specializations could be detected. In addition, a small

number of larger DA-immunoreactive cells were observed in

the lateral cell column at rostral levels. The lamprey spinal

cord thus contains distinct populations of synaptically

interconnected monoaminergic neurons. Dopamine-containing

LC cells synapse onto DA+5-HT-containing multipolar cells, in

addition to GABAergic LC cells and unidentified spinal neurons.

In contrast, the multipolar cells appear to exert their

influence by nonsynaptic mechanisms.. 0; 51-61-6; 56-12-2.

411. Schroder, J. M.; Kaldenbach, T.; Piroth, W. Nuclear and

mitochondrial changes of co-cultivated spinal cord, spinal

ganglia and muscle fibers following treatment with various

doses of zidovudine. Acta-Neuropathol-Berl. 1996 Aug; 92(2):

138-49; ISSN: 0001-6322.

GERMANY. Long-term zidovudine (also termed azidothymidine,

AZT) treatment of AIDS patients may cause severe myopathy

characterized by conspicuous mitochondrial and nuclear

changes. The mitochondrial changes are attributed to an

inhibitory effect of AZT on the mitochondrial gamma-

polymerase in a variety of cells. Inhibition of the nuclear

alpha-polymerase is another well-known side effect of AZT,

whereas the (nuclear) beta-polymerase appears to be rather

insensitive. The nuclear changes seen in AIDS patients are

usually considered secondary to the human immunodeficiency

virus infection. To eliminate the influence of the virus on the

nuclei, we studied the effect of AZT on non-infected,

organotypic co-cultures of spinal ganglia, spinal cord, and

skeletal muscle from fetal rats. We noted significant changes

not only in the mitochondria but also in the nuclei of spinal

ganglia, spinal cord, and muscle cells, which depended more on

the duration of AZT application (1, 3, 5, and 8 days) than on the

concentration (0.1, 1, 10, 100 and 1000 microM). The

alterations of the mitochondria consisted mainly of swelling,

loss of cristae and, finally, disappearance. The nuclei showed

nucleolar segregation, marginal condensation of

heterochromatin, formation of interchromatin and

perichromatin granules, nuclear protrusions and

pseudoinclusions and, finally, disintegration. The changes were

not as pleomorphic as those seen in biopsy specimens from

AIDS patients who had received long-term treatment with AZT.

However, this difference can easily be attributed to the short

duration of drug application in tissue culture compared to the

long-term medication in patients.. 30516-87-1.

412. Schroder, J. M.; Kaldenbach, T.; Piroth, W. Nuclear and

mitochondrial changes of co-cultivated spinal cord, spinal

ganglia and muscle fibers following treatment with various

doses of zidovudine. Acta-Neuropathol-Berl. 1996 Aug; 92(2):

138-49; ISSN: 0001-6322.

GERMANY. Long-term zidovudine (also termed azidothymidine,

AZT) treatment of AIDS patients may cause severe myopathy

characterized by conspicuous mitochondrial and nuclear

changes. The mitochondrial changes are attributed to an

inhibitory effect of AZT on the mitochondrial gamma-

polymerase in a variety of cells. Inhibition of the nuclear

alpha-polymerase is another well-known side effect of AZT,

whereas the (nuclear) beta-polymerase appears to be rather

insensitive. The nuclear changes seen in AIDS patients are

usually considered secondary to the human immunodeficiency

virus infection. To eliminate the influence of the virus on the

nuclei, we studied the effect of AZT on non-infected,

organotypic co-cultures of spinal ganglia, spinal cord, and

skeletal muscle from fetal rats. We noted significant changes

not only in the mitochondria but also in the nuclei of spinal

ganglia, spinal cord, and muscle cells, which depended more on

the duration of AZT application (1, 3, 5, and 8 days) than on the

concentration (0.1, 1, 10, 100 and 1000 microM). The

alterations of the mitochondria consisted mainly of swelling,

loss of cristae and, finally, disappearance. The nuclei showed

nucleolar segregation, marginal condensation of

heterochromatin, formation of interchromatin and

perichromatin granules, nuclear protrusions and

pseudoinclusions and, finally, disintegration. The changes were

not as pleomorphic as those seen in biopsy specimens from

AIDS patients who had received long-term treatment with AZT.

However, this difference can easily be attributed to the short

duration of drug application in tissue culture compared to the

long-term medication in patients.. 30516-87-1.

413. Scudder, C. A.; Moschovakis, A. K.; Karabelas, A. B.; Highstein, S. M.

Anatomy and physiology of saccadic long-lead burst neurons

recorded in the alert squirrel monkey. II. Pontine neurons. J-

Neurophysiol. 1996 Jul; 76(1): 353-70; ISSN: 0022-3077.

UNITED-STATES. 1. The discharge patterns and axonal

projections of saccadic long-lead burst neurons (LLBNs) with

somata in the pontine reticular formation were studied in

alert squirrel monkeys with the use of the method of

intraaxonal recording and horseradish peroxidase injection. 2.

The largest population of stained neurons were afferents to

the cerebellum. They originated in the dorsomedial nucleus

reticularis tegmenti pontis (NRTP) including its dorsal cell

group (N = 5), the preabducens intrafascicular nucleus (N = 5),

and the raphe pontis (N = 1). Axons of all neurons coursed under

NRTP and entered brachium pontis without having synapsed in

the brain stem. Three axons sent collaterals to the floccular

lobe, but other more distant targets of these and the other

cerebellar afferents could not be determined. Movement fields

of these neurons were intermediate between vectorial and

directional types. 3. Four neurons had their somata in nucleus

reticularis pontis oralis and terminations in the brain stem

reticular formation. Each neuron was different, but all

terminated in the region containing excitatory burst neurons,

and most terminated in the region containing inhibitory burst

neurons. Other targets include nucleus reticularis pontis oralis

and caudalis, NRTP, raphe interpositus, and the spinal cord.

Discharge patterns included both vectorial and directional

types. 4. Two reticulospinal neurons had large multipolar

somata either just rostral or ventral to the abducens nucleus.

These neurons also projected to the medullary reticular

formation, caudal nucleus prepositus hypoglossi, and dorsal

and ventral paramedian reticular nucleus. 5. The functional

implications of the connections of these LLBNs and those

reported in the companion paper are extensively discussed. The

fact that the efferents of the superior colliculus target the

regions containing medium-lead saccadic burst neurons

confirms the role of the colliculus in saccade generation.

However, the finding that many other neurons project to these

regions and the finding that superior colliculus efferents

project more heavily to areas containing reticulospinal

neurons argue for a diminished role of the superior colliculus

in saccade generation but an augmented role in head movement

control.

414. Scudder, C. A.; Moschovakis, A. K.; Karabelas, A. B.; Highstein, S. M.

Anatomy and physiology of saccadic long-lead burst neurons

recorded in the alert squirrel monkey. II. Pontine neurons. J-

Neurophysiol. 1996 Jul; 76(1): 353-70; ISSN: 0022-3077.

UNITED-STATES. 1. The discharge patterns and axonal

projections of saccadic long-lead burst neurons (LLBNs) with

somata in the pontine reticular formation were studied in

alert squirrel monkeys with the use of the method of

intraaxonal recording and horseradish peroxidase injection. 2.

The largest population of stained neurons were afferents to

the cerebellum. They originated in the dorsomedial nucleus

reticularis tegmenti pontis (NRTP) including its dorsal cell

group (N = 5), the preabducens intrafascicular nucleus (N = 5),

and the raphe pontis (N = 1). Axons of all neurons coursed under

NRTP and entered brachium pontis without having synapsed in

the brain stem. Three axons sent collaterals to the floccular

lobe, but other more distant targets of these and the other

cerebellar afferents could not be determined. Movement fields

of these neurons were intermediate between vectorial and

directional types. 3. Four neurons had their somata in nucleus

reticularis pontis oralis and terminations in the brain stem

reticular formation. Each neuron was different, but all

terminated in the region containing excitatory burst neurons,

and most terminated in the region containing inhibitory burst

neurons. Other targets include nucleus reticularis pontis oralis

and caudalis, NRTP, raphe interpositus, and the spinal cord.

Discharge patterns included both vectorial and directional

types. 4. Two reticulospinal neurons had large multipolar

somata either just rostral or ventral to the abducens nucleus.

These neurons also projected to the medullary reticular

formation, caudal nucleus prepositus hypoglossi, and dorsal

and ventral paramedian reticular nucleus. 5. The functional

implications of the connections of these LLBNs and those

reported in the companion paper are extensively discussed. The

fact that the efferents of the superior colliculus target the

regions containing medium-lead saccadic burst neurons

confirms the role of the colliculus in saccade generation.

However, the finding that many other neurons project to these

regions and the finding that superior colliculus efferents

project more heavily to areas containing reticulospinal

neurons argue for a diminished role of the superior colliculus

in saccade generation but an augmented role in head movement

control.

415. Serafini, T.; Colamarino, S. A.; Leonardo, E. D.; Wang, H.;

Beddington, R.; Skarnes, W. C.; Tessier Lavigne, M. Netrin-1 is

required for commissural axon guidance in the developing

vertebrate nervous system. Cell. 1996 Dec 13; 87(6): 1001-14;

ISSN: 0092-8674.

UNITED-STATES. During nervous system development, spinal

commissural axons project toward floor plate cells and

trochlear motor axons extend away from these cells. Netrin-1,

a diffusible protein made by floor plate cells, can attract

spinal commissural axons and repel trochlear axons in vitro,

but its role in vivo is unknown. Netrin-1 deficient mice exhibit

defects in spinal commissural axon projections that are

consistent with netrin-1 guiding these axons. Defects in

several forebrain commissures are also observed, suggesting

additional guidance roles for netrin-1. Trochlear axon

projections are largely normal, predicting the existence of

additional cues for these axons, and evidence is provided for a

distinct trochlear axon chemorepellent produced by floor plate

cells. These results establish netrin-1 as a guidance cue that

likely collaborates with other diffusible cues to guide axons in

vivo.. 0; 158651-98-0.

416. Serafini, T.; Colamarino, S. A.; Leonardo, E. D.; Wang, H.;

Beddington, R.; Skarnes, W. C.; Tessier Lavigne, M. Netrin-1 is

required for commissural axon guidance in the developing

vertebrate nervous system. Cell. 1996 Dec 13; 87(6): 1001-14;

ISSN: 0092-8674.

UNITED-STATES. During nervous system development, spinal

commissural axons project toward floor plate cells and

trochlear motor axons extend away from these cells. Netrin-1,

a diffusible protein made by floor plate cells, can attract

spinal commissural axons and repel trochlear axons in vitro,

but its role in vivo is unknown. Netrin-1 deficient mice exhibit

defects in spinal commissural axon projections that are

consistent with netrin-1 guiding these axons. Defects in

several forebrain commissures are also observed, suggesting

additional guidance roles for netrin-1. Trochlear axon

projections are largely normal, predicting the existence of

additional cues for these axons, and evidence is provided for a

distinct trochlear axon chemorepellent produced by floor plate

cells. These results establish netrin-1 as a guidance cue that

likely collaborates with other diffusible cues to guide axons in

vivo.. 0; 158651-98-0.

417. Shepherd, G. M. The dendritic spine: a multifunctional integrative

unit. J-Neurophysiol. 1996 Jun; 75(6): 2197-210; ISSN: 0022-

3077.

UNITED-STATES.

418. Shepherd, G. M. The dendritic spine: a multifunctional integrative

unit. J-Neurophysiol. 1996 Jun; 75(6): 2197-210; ISSN: 0022-

3077.

UNITED-STATES.

419. Shindo, M. [Spinal neural mechanisms in voluntary movements].

Rinsho-Shinkeigaku. 1995 Dec; 35(12): 1509-11; ISSN: 0009-

918X.

JAPAN. Spinal circuits are utilized not only in reflex

movements but also in voluntary movements. Their functions

are many-fold such as reciprocal inhibition, output control of

motoneurones, integration of central and peripheral inputs in

motoneurones, or increase in selectivity of muscle contraction

etc. The brain controls the activity of spinal circuits

depending on the movements required, by controlling the

activity of interneurones in the reflex pathways. In the case of

the soleus, the activity of reciprocal Ia inhibition and Ib

inhibition increases during voluntary contraction of the

antagonists. The increase in both inhibition takes place during

contraction as weak as 1-2% of the maximum, suggesting that

the interneurones can be fired by the descending commands

alone without any peripheral inputs. Such central control is

beneficial in suppressing stretch reflexes in the antagonistic

muscles which follows voluntary movements. On the other

hand, the activity of recurrent inhibition of the soleus is

enhanced during weak contraction of the muscle, but depressed

during medium strength contraction and strongly depressed

during strong contraction. Such supraspinal control of Renshaw

cells improves the balance between the preciseness in

controlling movements and the crude muscle power required.

Importance of spinal circuitry during voluntary movement

should be emphasized.

420. Shindo, M. [Spinal neural mechanisms in voluntary movements].

Rinsho-Shinkeigaku. 1995 Dec; 35(12): 1509-11; ISSN: 0009-

918X.

JAPAN. Spinal circuits are utilized not only in reflex

movements but also in voluntary movements. Their functions

are many-fold such as reciprocal inhibition, output control of

motoneurones, integration of central and peripheral inputs in

motoneurones, or increase in selectivity of muscle contraction

etc. The brain controls the activity of spinal circuits

depending on the movements required, by controlling the

activity of interneurones in the reflex pathways. In the case of

the soleus, the activity of reciprocal Ia inhibition and Ib

inhibition increases during voluntary contraction of the

antagonists. The increase in both inhibition takes place during

contraction as weak as 1-2% of the maximum, suggesting that

the interneurones can be fired by the descending commands

alone without any peripheral inputs. Such central control is

beneficial in suppressing stretch reflexes in the antagonistic

muscles which follows voluntary movements. On the other

hand, the activity of recurrent inhibition of the soleus is

enhanced during weak contraction of the muscle, but depressed

during medium strength contraction and strongly depressed

during strong contraction. Such supraspinal control of Renshaw

cells improves the balance between the preciseness in

controlling movements and the crude muscle power required.

Importance of spinal circuitry during voluntary movement

should be emphasized.

421. Shinoda, M.; Hoffer, B. J.; Olson, L. Interactions of neurotrophic

factors GDNF and NT-3, but not BDNF, with the immune system

following fetal spinal cord transplantation. Brain-Res. 1996

May 25; 722(1-2): 153-67; ISSN: 0006-8993.

NETHERLANDS. Glial cell line-derived neurotrophic factor

(GDNF) is known to stimulate survival of dopaminergic and

spinal cord motor neurons. However, little is known of the

possible immune sequelae of GDNF exposure, or that of other

putative trophic factors. To address these questions we

utilized in oculo grafts of spinal cord, wherein we could

induce different levels of immune responses via allogeneic vs.

syngeneic combinations. Adult female Sprague-Dawley and

Fisher rats were used as hosts for allogeneic and syngeneic

grafts, respectively. Embryonic age 14-15-day-old fetuses

were taken from pregnant dams of each strain, and cervical

spinal cords were removed and dissected. Pieces of the spinal

cord were transplanted into the anterior chamber of the eye

within each strain. At 5-day intervals, 0.5 microgram of GDNF,

brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-

3) or cytochrome c (CC) was injected into the anterior

chamber of the eye and the sizes of the transplants were

measured for the Sprague-Dawley rats. The same injections

and measurements, but only for GDNF and CC, were carried out

using Fisher rats. As expected, GDNF increased transplant

survival and growth in both the Sprague-Dawley and Fisher

animals. At day 41-42, all rats were sacrificed. Cameral graft

appearance was evaluated by cresyl violet and

immunohistochemically using antibodies against

neurofilament (NF), calcitonin gene-related peptide (CGRP) and

glial fibrillary acidic protein (GFAP). To monitor immune

responses, the following monoclonal antibodies were used:

OX38 against CD4, OX18 against MHC class I (MHCI), OX8

against CD8, OX6 against MHC class II (MHCII), OX42 against

CD11b, R73 against alpha and beta T cell receptor (TcR), and

ED1. In the Sprague-Dawley grafts, significantly higher

amounts of CD8+, T lymphocyte+, MHCI+ and MHCII+ antigen-

presenting cells (APC) were observed in GDNF-treated

transplants. These markers were also increased in NT-3-

treated groups. There were two types of OX-42+ cells, one was

the ordinary ramified microglial cell, the other appeared to be

a phagocytic cell, looking like the interstitial proliferating

variety. Interestingly, the phagocytic OX-42+ cells had the

same distribution as ED1+ and MHCII+ cells. In contrast, there

were few immunoreactive cells after GDNF treatment in the

inbred Fisher animals, similar to the CC control group. These

results suggest that GDNF and to some extent NT-3, can

activate the immune system in allogeneic graft combinations,

but that these trophic factors do not produce overt rejection,

and do not per se induce immune responses.. 0; 0; 0; 0; 0; 0.

422. Shinoda, M.; Hoffer, B. J.; Olson, L. Interactions of neurotrophic

factors GDNF and NT-3, but not BDNF, with the immune system

following fetal spinal cord transplantation. Brain-Res. 1996

May 25; 722(1-2): 153-67; ISSN: 0006-8993.

NETHERLANDS. Glial cell line-derived neurotrophic factor

(GDNF) is known to stimulate survival of dopaminergic and

spinal cord motor neurons. However, little is known of the

possible immune sequelae of GDNF exposure, or that of other

putative trophic factors. To address these questions we

utilized in oculo grafts of spinal cord, wherein we could

induce different levels of immune responses via allogeneic vs.

syngeneic combinations. Adult female Sprague-Dawley and

Fisher rats were used as hosts for allogeneic and syngeneic

grafts, respectively. Embryonic age 14-15-day-old fetuses

were taken from pregnant dams of each strain, and cervical

spinal cords were removed and dissected. Pieces of the spinal

cord were transplanted into the anterior chamber of the eye

within each strain. At 5-day intervals, 0.5 microgram of GDNF,

brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-

3) or cytochrome c (CC) was injected into the anterior

chamber of the eye and the sizes of the transplants were

measured for the Sprague-Dawley rats. The same injections

and measurements, but only for GDNF and CC, were carried out

using Fisher rats. As expected, GDNF increased transplant

survival and growth in both the Sprague-Dawley and Fisher

animals. At day 41-42, all rats were sacrificed. Cameral graft

appearance was evaluated by cresyl violet and

immunohistochemically using antibodies against

neurofilament (NF), calcitonin gene-related peptide (CGRP) and

glial fibrillary acidic protein (GFAP). To monitor immune

responses, the following monoclonal antibodies were used:

OX38 against CD4, OX18 against MHC class I (MHCI), OX8

against CD8, OX6 against MHC class II (MHCII), OX42 against

CD11b, R73 against alpha and beta T cell receptor (TcR), and

ED1. In the Sprague-Dawley grafts, significantly higher

amounts of CD8+, T lymphocyte+, MHCI+ and MHCII+ antigen-

presenting cells (APC) were observed in GDNF-treated

transplants. These markers were also increased in NT-3-

treated groups. There were two types of OX-42+ cells, one was

the ordinary ramified microglial cell, the other appeared to be

a phagocytic cell, looking like the interstitial proliferating

variety. Interestingly, the phagocytic OX-42+ cells had the

same distribution as ED1+ and MHCII+ cells. In contrast, there

were few immunoreactive cells after GDNF treatment in the

inbred Fisher animals, similar to the CC control group. These

results suggest that GDNF and to some extent NT-3, can

activate the immune system in allogeneic graft combinations,

but that these trophic factors do not produce overt rejection,

and do not per se induce immune responses.. 0; 0; 0; 0; 0; 0.

423. Shinoda, Y.; Kakei, S.; Muto, N. Morphology of single axons of

tectospinal and reticulospinal neurons in the upper cervical

spinal cord. Prog-Brain-Res. 1996; 112: 71-84; ISSN: 0079-

6123.

NETHERLANDS. Single axons of tectospinal (TS) and

reticulospinal (RS) neurons were stained with intraaxonal

injection of HRP after electrophysiological identification, and

their axonal trajectory was reconstructed at C1-C3 of the cat.

TS neurons were located in the intermediate or deep layers of

the caudal two-thirds of the superior colliculus (SC) and had

multiple axon collaterals (up to seven collaterals) per stem

axon). Collaterals had a simple structure, ramified several

times mainly in the transverse plane, and terminated in the

lateral parts of laminae V-VIII. More than half also had

terminals in lamina IX. Terminals of TS neurons did not appear

to make contacts with either the somas or proximal dendrites

of retrogradely-labeled motoneurons in lamina IX, but clear

contacts were found on counterstained interneurons in the

lateral part of laminae V-VIII. Here, we examined three

stained spinal interneurons receiving monosynaptic excitation

from the SC. These interneurons had multiple axon collaterals

mainly in laminae VII-IX, and made extensive contacts with

retrogradely-labeled motoneurons of multiple neck muscles.

Stem axons of single RS neurons receiving input from the

contralateral SC ran in the ventromedial funiculus and gave off

multiple axon collaterals to laminae VII-IX over at least

several cervical segments. Their terminal boutons appeared to

make contact with both the somas and proximal dendrites of

retrogradely-labeled neck motoneurons. Single RS neurons

made contacts with motoneurons of different neck muscles.

These results provide evidence for functional synergies at the

level of single RS neurons and spinal interneurons for neck

movements. The present finding indicates that the direct TS

projection to the spinal cord may influence the activity of

multiple neck muscles mainly via spinal interneurons, and

plays an important role in control of head movement in

parallel with the tecto-reticulospinal system.

424. Shinoda, Y.; Kakei, S.; Muto, N. Morphology of single axons of

tectospinal and reticulospinal neurons in the upper cervical

spinal cord. Prog-Brain-Res. 1996; 112: 71-84; ISSN: 0079-

6123.

NETHERLANDS. Single axons of tectospinal (TS) and

reticulospinal (RS) neurons were stained with intraaxonal

injection of HRP after electrophysiological identification, and

their axonal trajectory was reconstructed at C1-C3 of the cat.

TS neurons were located in the intermediate or deep layers of

the caudal two-thirds of the superior colliculus (SC) and had

multiple axon collaterals (up to seven collaterals) per stem

axon). Collaterals had a simple structure, ramified several

times mainly in the transverse plane, and terminated in the

lateral parts of laminae V-VIII. More than half also had

terminals in lamina IX. Terminals of TS neurons did not appear

to make contacts with either the somas or proximal dendrites

of retrogradely-labeled motoneurons in lamina IX, but clear

contacts were found on counterstained interneurons in the

lateral part of laminae V-VIII. Here, we examined three

stained spinal interneurons receiving monosynaptic excitation

from the SC. These interneurons had multiple axon collaterals

mainly in laminae VII-IX, and made extensive contacts with

retrogradely-labeled motoneurons of multiple neck muscles.

Stem axons of single RS neurons receiving input from the

contralateral SC ran in the ventromedial funiculus and gave off

multiple axon collaterals to laminae VII-IX over at least

several cervical segments. Their terminal boutons appeared to

make contact with both the somas and proximal dendrites of

retrogradely-labeled neck motoneurons. Single RS neurons

made contacts with motoneurons of different neck muscles.

These results provide evidence for functional synergies at the

level of single RS neurons and spinal interneurons for neck

movements. The present finding indicates that the direct TS

projection to the spinal cord may influence the activity of

multiple neck muscles mainly via spinal interneurons, and

plays an important role in control of head movement in

parallel with the tecto-reticulospinal system.

425. Shinomiya, K.; Mochida, K.; Komori, H.; Mutoh, N.; Okawa, A.

Monitoring of anterior cervical spinal cord function. J-Spinal-

Disord. 1996 Jun; 9(3): 187-94; ISSN: 0895-0385.

UNITED-STATES. Anterior surgery is frequently chosen for

treatment of cervical myelopathy. However, intraoperative

spinal cord recording has rarely been used to monitor the

function of the ventral columns. We report a method of

monitoring evoked spinal cord potentials useful for detection

of minor injury of the anterior spinal cord. Evoked spinal cord

potentials elicited in cats by thoracic spinal cord and

labyrinth stimulation were studied. Evoked intraspinal field

potentials recorded after labyrinth stimulation were

confirmed to originate from the vestibulospinal tract in the

ventral columns. Low-amplitude potentials were recorded

from the posterior epidural space. However, this method has

not been used clinically because of difficulty in obtaining

selective stimulation in humans. Spinal cord potentials evoked

by thoracic stimulation were recorded from the anterior and

posterior epidural spaces. The amplitude of the potentials was

large enough to permit quantitation of neural function. We

confirmed that anterior recording was more sensitive in

detecting ventral column injury than posterior recording was.

Based on these findings, we used anterior recording from the

disc clinically for anterior spinal cord monitoring during

anterior cervical surgery.

426. Shinomiya, K.; Mochida, K.; Komori, H.; Mutoh, N.; Okawa, A.

Monitoring of anterior cervical spinal cord function. J-Spinal-

Disord. 1996 Jun; 9(3): 187-94; ISSN: 0895-0385.

UNITED-STATES. Anterior surgery is frequently chosen for

treatment of cervical myelopathy. However, intraoperative

spinal cord recording has rarely been used to monitor the

function of the ventral columns. We report a method of

monitoring evoked spinal cord potentials useful for detection

of minor injury of the anterior spinal cord. Evoked spinal cord

potentials elicited in cats by thoracic spinal cord and

labyrinth stimulation were studied. Evoked intraspinal field

potentials recorded after labyrinth stimulation were

confirmed to originate from the vestibulospinal tract in the

ventral columns. Low-amplitude potentials were recorded

from the posterior epidural space. However, this method has

not been used clinically because of difficulty in obtaining

selective stimulation in humans. Spinal cord potentials evoked

by thoracic stimulation were recorded from the anterior and

posterior epidural spaces. The amplitude of the potentials was

large enough to permit quantitation of neural function. We

confirmed that anterior recording was more sensitive in

detecting ventral column injury than posterior recording was.

Based on these findings, we used anterior recording from the

disc clinically for anterior spinal cord monitoring during

anterior cervical surgery.

427. Sim, K. B.; Wang, K. C.; Cho, B. K. Terminal myelocystocele--a case

report. J-Korean-Med-Sci. 1996 Apr; 11(2): 197-202; ISSN:

1011-8934.

KOREA. Terminal myelocystocele is a rare form of occult

spinal dysraphism in which the hydromyelic caudal spinal cord

and the subarachnoid space are hemiated through a posterior

spina bifida. A 1.5 month old boy presented with a large

lumbosacral mass and urinary incontinence. The magnetic

resonance imaging, operative findings and pathological

findings revealed a low lying conus with a dilated central

canal dorsally attached to the subcutaneous tissue. Ventral

subarachnoid space was enlarged and herniated through the

laminar defect of the sacrum. The lesion was typical of a

terminal myelocystocele. The clinical features are different

from those of myelomeningocele in many aspects. Though the

incidence is low, terminal myelocystocele should be included

in the differential diagnosis of congenital lesions presenting

as a lumbosacral mass.

428. Sim, K. B.; Wang, K. C.; Cho, B. K. Terminal myelocystocele--a case

report. J-Korean-Med-Sci. 1996 Apr; 11(2): 197-202; ISSN:

1011-8934.

KOREA. Terminal myelocystocele is a rare form of occult

spinal dysraphism in which the hydromyelic caudal spinal cord

and the subarachnoid space are hemiated through a posterior

spina bifida. A 1.5 month old boy presented with a large

lumbosacral mass and urinary incontinence. The magnetic

resonance imaging, operative findings and pathological

findings revealed a low lying conus with a dilated central

canal dorsally attached to the subcutaneous tissue. Ventral

subarachnoid space was enlarged and herniated through the

laminar defect of the sacrum. The lesion was typical of a

terminal myelocystocele. The clinical features are different

from those of myelomeningocele in many aspects. Though the

incidence is low, terminal myelocystocele should be included

in the differential diagnosis of congenital lesions presenting

as a lumbosacral mass.

429. Sloan, T. B. Evoked potential monitoring. Int-Anesthesiol-Clin.

1996 Jun; 34(3): 109-36; ISSN: 0020-5907.

UNITED-STATES.

430. Sloan, T. B. Evoked potential monitoring. Int-Anesthesiol-Clin.

1996 Jun; 34(3): 109-36; ISSN: 0020-5907.

UNITED-STATES.

431. Snow, D. M.; Brown, E. M.; Letourneau, P. C. Growth cone behavior in

the presence of soluble chondroitin sulfate proteoglycan

(CSPG), compared to behavior on CSPG bound to laminin or

fibronectin. Int-J-Dev-Neurosci. 1996 Jun; 14(3): 331-49;

ISSN: 0736-5748.

ENGLAND. Proteoglycans (PGs) are complex macromolecules of

the extracellular matrix (ECM) that have a wide variety of

effects on developing and regenerating neurons in vivo and in

vitro. One hypothesis regarding the mechanisms of PG

regulation of neuronal behavior states that the conformation

of PGs may be critical, and thus that ECM- or cell surface-

bound PGs may operate differently than secreted (soluble) PGs.

Therefore, this study examined differences between the

effects of soluble chondroitin sulfate proteoglycan (CSPG) and

substratum-bound CSPG on neuronal growth cone behavior.

Dissociated chicken dorsal root ganglion (DRG) neurons were

cultured on either laminin (LN) or fibronectin (FN), both

sensory neurite outgrowth-promotin glycoproteins. CSPG (or

chondroitin sulfate alone) was either bound to FN or LN, or was

added to the culture media. Subsequently, using time lapse

video microscopy and image analysis, this study measured: (1)

neuronal attachment, (2) neurite outgrowth, (3) rate of neurite

elongation, and (4) filopodial length and lifespan. To determine

the site of CSPG action, DRG neurons were grown on either:

CS-1, a FN peptide [Humphries M. J. et al. (1987) J. biol. Chem.

262, 6886-6892], or a recombinant FN protein, RFNIIIcs

(Maejne, submitted), both of which permit DRG attachment and

outgrowth but do not have recognized CSPG binding sites, and

the resulting neuronal behavior was compared to that of DRG

neurons grown on intact FN. The results of these studies

confirm that the effect of CSPG on DRG neurons is

concentration-, conformation- and substratum-dependent. On

I.N, soluble CSPG had little to no effect on neurite initiation or

outgrowth, while substratum-bound CSPG inhibited neurite

outgrowth. In contrast, on FN, soluble CSPG inhibited neurite

outgrowth and decreased the rate of neurite elongation.

Soluble CSPG did not affect the length of sensory growth cone

filopodia or filopodial lifespan on either LN or FN. From the FN

fragment experiments, we found that: (1) soluble CSPG reduces

neurite outgrowth on FN or FN fragments, but not on LN, up to

80%, and reduces elongation rate on FN up to 50%, and (2)

soluble CSPG regulates neuronal behavior by binding directly

to growth cones elongating on FN. Given that substratum-bound

CSPG from a variety of sources is inhibitory to neurite

outgrowth and to the rate of neurite elongation, while soluble

CSPG often has different effects on growth cone behavior, the

regulation of growth cone behavior by CSPGs may be dependent

upon CSPG conformation. Further, CSPG may affect growth

cone behavior by either binding to the substratum or by binding

directly to growth cones.. 0; 0; 0; 9007-28-7.

432. Snow, D. M.; Brown, E. M.; Letourneau, P. C. Growth cone behavior in

the presence of soluble chondroitin sulfate proteoglycan

(CSPG), compared to behavior on CSPG bound to laminin or

fibronectin. Int-J-Dev-Neurosci. 1996 Jun; 14(3): 331-49;

ISSN: 0736-5748.

ENGLAND. Proteoglycans (PGs) are complex macromolecules of

the extracellular matrix (ECM) that have a wide variety of

effects on developing and regenerating neurons in vivo and in

vitro. One hypothesis regarding the mechanisms of PG

regulation of neuronal behavior states that the conformation

of PGs may be critical, and thus that ECM- or cell surface-

bound PGs may operate differently than secreted (soluble) PGs.

Therefore, this study examined differences between the

effects of soluble chondroitin sulfate proteoglycan (CSPG) and

substratum-bound CSPG on neuronal growth cone behavior.

Dissociated chicken dorsal root ganglion (DRG) neurons were

cultured on either laminin (LN) or fibronectin (FN), both

sensory neurite outgrowth-promotin glycoproteins. CSPG (or

chondroitin sulfate alone) was either bound to FN or LN, or was

added to the culture media. Subsequently, using time lapse

video microscopy and image analysis, this study measured: (1)

neuronal attachment, (2) neurite outgrowth, (3) rate of neurite

elongation, and (4) filopodial length and lifespan. To determine

the site of CSPG action, DRG neurons were grown on either:

CS-1, a FN peptide [Humphries M. J. et al. (1987) J. biol. Chem.

262, 6886-6892], or a recombinant FN protein, RFNIIIcs

(Maejne, submitted), both of which permit DRG attachment and

outgrowth but do not have recognized CSPG binding sites, and

the resulting neuronal behavior was compared to that of DRG

neurons grown on intact FN. The results of these studies

confirm that the effect of CSPG on DRG neurons is

concentration-, conformation- and substratum-dependent. On

I.N, soluble CSPG had little to no effect on neurite initiation or

outgrowth, while substratum-bound CSPG inhibited neurite

outgrowth. In contrast, on FN, soluble CSPG inhibited neurite

outgrowth and decreased the rate of neurite elongation.

Soluble CSPG did not affect the length of sensory growth cone

filopodia or filopodial lifespan on either LN or FN. From the FN

fragment experiments, we found that: (1) soluble CSPG reduces

neurite outgrowth on FN or FN fragments, but not on LN, up to

80%, and reduces elongation rate on FN up to 50%, and (2)

soluble CSPG regulates neuronal behavior by binding directly

to growth cones elongating on FN. Given that substratum-bound

CSPG from a variety of sources is inhibitory to neurite

outgrowth and to the rate of neurite elongation, while soluble

CSPG often has different effects on growth cone behavior, the

regulation of growth cone behavior by CSPGs may be dependent

upon CSPG conformation. Further, CSPG may affect growth

cone behavior by either binding to the substratum or by binding

directly to growth cones.. 0; 0; 0; 9007-28-7.

433. Soffe, S. R. Motor patterns for two distinct rhythmic behaviors

evoked by excitatory amino acid agonists in the Xenopus

embryo spinal cord. J-Neurophysiol. 1996 May; 75(5): 1815-25;

ISSN: 0022-3077.

UNITED-STATES. 1. Mechanisms underlying the selective

expression of different motor patterns in vertebrates are

poorly understood. Immobilized, spinal Xenopus embryos are

used here to examine the motor patterns evoked by various

concentrations of excitatory amino acids. 2. Relatively low

concentrations of N-methyl-D-aspartate (NMDA) (40-60

microM), kainate (7-8 microM), and alpha-amino-3-hydroxy-5-

methyl-4-isoxazolepropionate (AMPA) (5 microM) evoked

motor root discharge characteristic of swimming. Brief

applications of higher concentrations of kainate (20-40

microM), AMPA (25-30 microM), quisqualate (5 microM), and

glutamate (1-4 mM) evoked sequences of a different motor

pattern: struggling. This is characterized by a longer cycle

period, increased burst duration, and a reversed longitudinal

pattern of motor root discharge. The struggling pattern was

never evoked by higher concentrations of NMDA (300-500

microM), but was evoked by 30 microM AMPA or 5 microM

quisqualate in the presence of 50 microM D-2-amino-5-

phosphonopentanoic acid. 3. Intracellular recordings from

presumed spinal motoneurons showed different patterns of

activity during agonist-evoked swimming and struggling. The

patterns were like those described previously during sensory-

evoked behavior. 4. Caudal applications of excitatory amino

acids that produced struggling discharge did so only at caudal

motor roots, whereas caudal applications of NMDA evoked

swimming activity throughout the spinal cord. 5. During

excitatory-amino-acid-evoked struggling, sensory Rohon-

Beard neurons depolarized up to 7 mV, but did not fire. 6. The

results show that expression of the struggling pattern, like

swimming, is not critically dependent on sensory discharge.

The results are also consistent with the idea that expression

of the two very different motor patterns for swimming or

struggling in this simple vertebrate preparation can be

controlled by the level of excitation within the spinal motor

circuitry, and need not involve the activity of a specific

external neuromodulator.. 0; 0.

434. Soffe, S. R. Motor patterns for two distinct rhythmic behaviors

evoked by excitatory amino acid agonists in the Xenopus

embryo spinal cord. J-Neurophysiol. 1996 May; 75(5): 1815-25;

ISSN: 0022-3077.

UNITED-STATES. 1. Mechanisms underlying the selective

expression of different motor patterns in vertebrates are

poorly understood. Immobilized, spinal Xenopus embryos are

used here to examine the motor patterns evoked by various

concentrations of excitatory amino acids. 2. Relatively low

concentrations of N-methyl-D-aspartate (NMDA) (40-60

microM), kainate (7-8 microM), and alpha-amino-3-hydroxy-5-

methyl-4-isoxazolepropionate (AMPA) (5 microM) evoked

motor root discharge characteristic of swimming. Brief

applications of higher concentrations of kainate (20-40

microM), AMPA (25-30 microM), quisqualate (5 microM), and

glutamate (1-4 mM) evoked sequences of a different motor

pattern: struggling. This is characterized by a longer cycle

period, increased burst duration, and a reversed longitudinal

pattern of motor root discharge. The struggling pattern was

never evoked by higher concentrations of NMDA (300-500

microM), but was evoked by 30 microM AMPA or 5 microM

quisqualate in the presence of 50 microM D-2-amino-5-

phosphonopentanoic acid. 3. Intracellular recordings from

presumed spinal motoneurons showed different patterns of

activity during agonist-evoked swimming and struggling. The

patterns were like those described previously during sensory-

evoked behavior. 4. Caudal applications of excitatory amino

acids that produced struggling discharge did so only at caudal

motor roots, whereas caudal applications of NMDA evoked

swimming activity throughout the spinal cord. 5. During

excitatory-amino-acid-evoked struggling, sensory Rohon-

Beard neurons depolarized up to 7 mV, but did not fire. 6. The

results show that expression of the struggling pattern, like

swimming, is not critically dependent on sensory discharge.

The results are also consistent with the idea that expression

of the two very different motor patterns for swimming or

struggling in this simple vertebrate preparation can be

controlled by the level of excitation within the spinal motor

circuitry, and need not involve the activity of a specific

external neuromodulator.. 0; 0.

435. Stanfa, L. C.; Misra, C.; Dickenson, A. H. Amplification of spinal

nociceptive transmission depends on the generation of nitric

oxide in normal and carrageenan rats. Brain-Res. 1996 Oct 21;

737(1-2): 92-8; ISSN: 0006-8993.

NETHERLANDS. It has been proposed that nitric oxide (NO) is

involved in the spinal transmission of nociceptive information,

particularly following the development of peripheral

inflammation. In this electrophysiological study the ability of

the nitric oxide synthase inhibitor 7-nitro indazole (7-NI),

which does not block endothelial nitric oxide in vivo, to inhibit

the electrically evoked responses of dorsal horn neurones

recorded in both normal animals and in animals 3 h after the

injection of carrageenan into the ipsilateral hind paw, was

investigated. In both normal and carrageenan inflamed animals,

7-NI (1-100 micrograms), administered intrathecally, strongly

inhibited the NMDA receptor mediated wind-up and post-

discharge of the neurones, having relatively little effect on

the acute C- or A beta-fibre evoked activity of the neurones.

This inhibitory action of 7-NI on the noxious evoked responses

of the neurones was completely blocked by the prior

intrathecal administration of 500 micrograms of L-arginine.

Inflammation did not alter the effects of 7-NI since there was

no difference in the dose-response curve between the normal

and carrageenan animals. In normal animals, stimuli of

sufficient duration/intensity to enable the activation of NMDA

receptors to occur, shown in this study by the occurrence of

wind-up, also lead to the generation of nitric oxide, which

then participates in nociceptive transmission. These effects

appear to be independent of the vascular effects of NO.

Inflammation-induced changes could facilitate activation of

spinal NMDA receptors, such that nitric oxide is now generated

by stimuli previously sub-threshold for this event. Previous

studies, reporting a unique role of NO in nociceptive

transmission following the development of peripheral

inflammation, may have resulted from inadequate stimuli in

the normal animal.. 0; 0; 0; 10102-43-9; 2942-42-9; 7004-

12-8; 9000-07-1.

436. Stanfa, L. C.; Misra, C.; Dickenson, A. H. Amplification of spinal

nociceptive transmission depends on the generation of nitric

oxide in normal and carrageenan rats. Brain-Res. 1996 Oct 21;

737(1-2): 92-8; ISSN: 0006-8993.

NETHERLANDS. It has been proposed that nitric oxide (NO) is

involved in the spinal transmission of nociceptive information,

particularly following the development of peripheral

inflammation. In this electrophysiological study the ability of

the nitric oxide synthase inhibitor 7-nitro indazole (7-NI),

which does not block endothelial nitric oxide in vivo, to inhibit

the electrically evoked responses of dorsal horn neurones

recorded in both normal animals and in animals 3 h after the

injection of carrageenan into the ipsilateral hind paw, was

investigated. In both normal and carrageenan inflamed animals,

7-NI (1-100 micrograms), administered intrathecally, strongly

inhibited the NMDA receptor mediated wind-up and post-

discharge of the neurones, having relatively little effect on

the acute C- or A beta-fibre evoked activity of the neurones.

This inhibitory action of 7-NI on the noxious evoked responses

of the neurones was completely blocked by the prior

intrathecal administration of 500 micrograms of L-arginine.

Inflammation did not alter the effects of 7-NI since there was

no difference in the dose-response curve between the normal

and carrageenan animals. In normal animals, stimuli of

sufficient duration/intensity to enable the activation of NMDA

receptors to occur, shown in this study by the occurrence of

wind-up, also lead to the generation of nitric oxide, which

then participates in nociceptive transmission. These effects

appear to be independent of the vascular effects of NO.

Inflammation-induced changes could facilitate activation of

spinal NMDA receptors, such that nitric oxide is now generated

by stimuli previously sub-threshold for this event. Previous

studies, reporting a unique role of NO in nociceptive

transmission following the development of peripheral

inflammation, may have resulted from inadequate stimuli in

the normal animal.. 0; 0; 0; 10102-43-9; 2942-42-9; 7004-

12-8; 9000-07-1.

437. Stebbins, C. L. Mechanisms underlying spinal neuromodulation of

the exercise pressor reflex. Adv-Exp-Med-Biol. 1995; 381:

209-13; ISSN: 0065-2598.

UNITED-STATES. 0; 113-79-1; 50-56-6.

438. Stebbins, C. L. Mechanisms underlying spinal neuromodulation of

the exercise pressor reflex. Adv-Exp-Med-Biol. 1995; 381:

209-13; ISSN: 0065-2598.

UNITED-STATES. 0; 113-79-1; 50-56-6.

439. Struijk, J. J.; Holsheimer, J. Transverse tripolar spinal cord

stimulation: theoretical performance of a dual channel system.

Med-Biol-Eng-Comput. 1996 Jul; 34(4): 273-9; ISSN: 0140-

0118.

ENGLAND. A new approach to spinal cord stimulation is

presented, by which several serious problems of conventional

methods can be solved. A transverse tripolar electrode with a

dual-channel voltage stimulator is evaluated theoretically by

means of a volume conductor model, combined with nerve fibre

models. The simulations predict that a high degree of freedom

in the control of activation of dorsal spinal pathways may be

obtained with the described system. This implies an easier

control of paraesthesia coverage of skin areas and the

possibility to correct undesired paraesthesia patterns, caused

by lead migration, tissue growth, or anatomical asymmetries,

for example, without surgical intervention. It will also be

possible to preferentially activate either dorsal column or

dorsal root fibres, which has some important clinical

advantages. Compared to conventional stimulation systems,

the new system has a relatively high current drain.

440. Struijk, J. J.; Holsheimer, J. Transverse tripolar spinal cord

stimulation: theoretical performance of a dual channel system.

Med-Biol-Eng-Comput. 1996 Jul; 34(4): 273-9; ISSN: 0140-

0118.

ENGLAND. A new approach to spinal cord stimulation is

presented, by which several serious problems of conventional

methods can be solved. A transverse tripolar electrode with a

dual-channel voltage stimulator is evaluated theoretically by

means of a volume conductor model, combined with nerve fibre

models. The simulations predict that a high degree of freedom

in the control of activation of dorsal spinal pathways may be

obtained with the described system. This implies an easier

control of paraesthesia coverage of skin areas and the

possibility to correct undesired paraesthesia patterns, caused

by lead migration, tissue growth, or anatomical asymmetries,

for example, without surgical intervention. It will also be

possible to preferentially activate either dorsal column or

dorsal root fibres, which has some important clinical

advantages. Compared to conventional stimulation systems,

the new system has a relatively high current drain.

441. Takada, T.; Denda, S.; Baba, H.; Fujioka, H.; Yamakura, T.; Fujihara,

H.; Taga, K.; Fukuda, S.; Shimoji, K. Somatosensory evoked

potentials recorded from the posterior pharynx to stimulation

of the median nerve and cauda equina. Electroencephalogr-

Clin-Neurophysiol. 1996 Nov; 100(6): 493-9; ISSN: 0013-4694.

IRELAND. Somatosensory evoked potentials (ppSEPs) in

response to stimulation of the median nerve at the wrist and

the cauda equina at the epidural space (the L4 level) were

recorded from the posterior wall of the pharynx in 15 patients

who underwent spinal surgery under general anesthesia, using

disc electrodes attached to the endotracheal tube, and

compared with segmental spinal cord potentials (seg-SCPs)

that were recorded simultaneously from the posterior epidural

space (PES). ppSEPs consisted of the initially positive spike

(P9) followed by slow positive (P13) and negative (N22)

waves. The P13 and N22 of ppSEPs had phase reversal

relationship with the P2 and N2 recorded from the PES,

respectively. The peak latencies of P9 (9.40 +/- 0.7 ms) (mean

+/- SD), P13 (13.1 +/- 0.9 ms), and N22 (22.0 +/- 2.1 ms) of

ppSEPs coincided with those of P1, N1 and P2 of seg-SCPs,

respectively, ppSEPs were recorded more clearly with a

reference electrode on the dorsal surface of the neck than

with the reference electrode at the earlobe or back of the

hand. The threshold and maximal stimulus intensities were

also similar between the ppSEPs and seg-SCPs. Thus, the P9,

P13, and N22 components of ppSEPs were thought to have the

same origin as the P1, N1 and P2 of seg-SCPs, respectively.

Therefore, the P9, P13 and N22 of ppSEPs may reflect

incoming volleys through the root, synchronized activities of

the interneurons and primary afferent depolarizations (PAD),

respectively. ppSEPs in response to cauda equina stimulation

showed that the latencies of the two initial components (4.6

+/- 0.4 and 6.4 +/- 0.6 ms) corresponded to those of the SCPs

recorded from the PES (4.6 +/- 0.3 and 6.3 +/- 0.5 ms),

suggesting that these potentials reflect impulses conducting

through the spinal cord, similar to epidurally recorded SCPs.

442. Takada, T.; Denda, S.; Baba, H.; Fujioka, H.; Yamakura, T.; Fujihara,

H.; Taga, K.; Fukuda, S.; Shimoji, K. Somatosensory evoked

potentials recorded from the posterior pharynx to stimulation

of the median nerve and cauda equina. Electroencephalogr-

Clin-Neurophysiol. 1996 Nov; 100(6): 493-9; ISSN: 0013-4694.

IRELAND. Somatosensory evoked potentials (ppSEPs) in

response to stimulation of the median nerve at the wrist and

the cauda equina at the epidural space (the L4 level) were

recorded from the posterior wall of the pharynx in 15 patients

who underwent spinal surgery under general anesthesia, using

disc electrodes attached to the endotracheal tube, and

compared with segmental spinal cord potentials (seg-SCPs)

that were recorded simultaneously from the posterior epidural

space (PES). ppSEPs consisted of the initially positive spike

(P9) followed by slow positive (P13) and negative (N22)

waves. The P13 and N22 of ppSEPs had phase reversal

relationship with the P2 and N2 recorded from the PES,

respectively. The peak latencies of P9 (9.40 +/- 0.7 ms) (mean

+/- SD), P13 (13.1 +/- 0.9 ms), and N22 (22.0 +/- 2.1 ms) of

ppSEPs coincided with those of P1, N1 and P2 of seg-SCPs,

respectively, ppSEPs were recorded more clearly with a

reference electrode on the dorsal surface of the neck than

with the reference electrode at the earlobe or back of the

hand. The threshold and maximal stimulus intensities were

also similar between the ppSEPs and seg-SCPs. Thus, the P9,

P13, and N22 components of ppSEPs were thought to have the

same origin as the P1, N1 and P2 of seg-SCPs, respectively.

Therefore, the P9, P13 and N22 of ppSEPs may reflect

incoming volleys through the root, synchronized activities of

the interneurons and primary afferent depolarizations (PAD),

respectively. ppSEPs in response to cauda equina stimulation

showed that the latencies of the two initial components (4.6

+/- 0.4 and 6.4 +/- 0.6 ms) corresponded to those of the SCPs

recorded from the PES (4.6 +/- 0.3 and 6.3 +/- 0.5 ms),

suggesting that these potentials reflect impulses conducting

through the spinal cord, similar to epidurally recorded SCPs.

443. Takeuchi, Y.; Itoh, M.; Miki, T.; Chen, X. H.; Sun, W. Hypoglossal

afferents to lamina I neurons of the cervical spinal cord

projecting to the parabrachial nucleus in the cat. Somatosens-

Mot-Res. 1995; 12(3-4): 191-8; ISSN: 0899-0220.

ENGLAND. Attempts were made to determine the hypoglossal

sensory inputs to the parabrachial nucleus (PBN) through the

spinal cord. Wheatgerm agglutinin conjugated to horseradish

peroxidase (WGA:HRP) was injected into the cat hypoglossal

nerve. HRP-labeled fibers, predominantly derived from the

glossopharyngeal and vagal nerves, were observed to terminate

in lamina I of the upper cervical spinal cord. A few fibers were

also distributed to laminae IV-V and VII-VIII ipsilaterally.

WGA:HRP injection into the lateral portion of the PBN also

resulted in retrograde labeling in lamina I with ipsilateral

predominance. Light-microscopic data raised the possibility of

a relay of hypoglossal sensory information to the PBN in

lamina I of the cervical spinal cord. In order to confirm the

spinal relay, electron-microscopic observations were carried

out on lamina I of C1 spinal cord after sectioning of the

hypoglossal nerve and WGA:HRP injection into the lateral

portion of the PBN on the same side in each animal. It was of

particular interest that degenerated hypoglossal afferent

fibers made synaptic contacts with lamina I neurons, which

were retrogradely labeled with HRP.

444. Takeuchi, Y.; Itoh, M.; Miki, T.; Chen, X. H.; Sun, W. Hypoglossal

afferents to lamina I neurons of the cervical spinal cord

projecting to the parabrachial nucleus in the cat. Somatosens-

Mot-Res. 1995; 12(3-4): 191-8; ISSN: 0899-0220.

ENGLAND. Attempts were made to determine the hypoglossal

sensory inputs to the parabrachial nucleus (PBN) through the

spinal cord. Wheatgerm agglutinin conjugated to horseradish

peroxidase (WGA:HRP) was injected into the cat hypoglossal

nerve. HRP-labeled fibers, predominantly derived from the

glossopharyngeal and vagal nerves, were observed to terminate

in lamina I of the upper cervical spinal cord. A few fibers were

also distributed to laminae IV-V and VII-VIII ipsilaterally.

WGA:HRP injection into the lateral portion of the PBN also

resulted in retrograde labeling in lamina I with ipsilateral

predominance. Light-microscopic data raised the possibility of

a relay of hypoglossal sensory information to the PBN in

lamina I of the cervical spinal cord. In order to confirm the

spinal relay, electron-microscopic observations were carried

out on lamina I of C1 spinal cord after sectioning of the

hypoglossal nerve and WGA:HRP injection into the lateral

portion of the PBN on the same side in each animal. It was of

particular interest that degenerated hypoglossal afferent

fibers made synaptic contacts with lamina I neurons, which

were retrogradely labeled with HRP.

445. Tanabe, Y.; Jessell, T. M. Diversity and pattern in the developing

spinal cord. Science. 1996 Nov 15; 274(5290): 1115-23; ISSN:

0036-8075.

UNITED-STATES. The generation of distinct neuronal cell

types in appropriate numbers and at precise positions

underlies the assembly of neural circuits that encode animal

behavior. Despite the complexity of the vertebrate central

nervous system, advances have been made in defining the

principles that control the diversification and patterning of

its component cells. A combination of molecular genetic,

biochemical, and embryological assays has begun to reveal the

identity and mechanism of action of molecules that induce and

pattern neural tissue and the role of transcription factors in

establishing generic and specific neuronal fates. Some of

these advances are discussed here, focusing on the spinal cord

as a model system for analyzing the molecular control of

central nervous system development in vertebrates.. 0.

446. Tanabe, Y.; Jessell, T. M. Diversity and pattern in the developing

spinal cord. Science. 1996 Nov 15; 274(5290): 1115-23; ISSN:

0036-8075.

UNITED-STATES. The generation of distinct neuronal cell

types in appropriate numbers and at precise positions

underlies the assembly of neural circuits that encode animal

behavior. Despite the complexity of the vertebrate central

nervous system, advances have been made in defining the

principles that control the diversification and patterning of

its component cells. A combination of molecular genetic,

biochemical, and embryological assays has begun to reveal the

identity and mechanism of action of molecules that induce and

pattern neural tissue and the role of transcription factors in

establishing generic and specific neuronal fates. Some of

these advances are discussed here, focusing on the spinal cord

as a model system for analyzing the molecular control of

central nervous system development in vertebrates.. 0.

447. Tani, T.; Ushida, T.; Yamamoto, H.; Okuhara, Y. Waveform changes

due to conduction block and their underlying mechanism in

spinal somatosensory evoked potential: a computer simulation.

Technical note. J-Neurosurg. 1997 Feb; 86(2): 303-10; ISSN:

0022-3085.

UNITED-STATES. Based on a square-wave solid-angle analysis,

a simplified mathematical model was produced for computing

a sequence of potential change in a volume conductor

generated by an impulse traveling along a nerve fiber. A

conduction block was simulated as a phenomenon in which a

depolarization wavefront stops traveling when it reaches a

certain point, although the following repolarization wavefront

continues to travel until it reaches the same point. The spinal

somatosensory evoked potential (SSEP) was produced as an

algebraic sum of simulated nerve fiber action potentials

(NFAPs). With a conduction block, an NFAP that was normally

triphasic showed a positive-negative diphasic wave with

reduced negativity at the point of the block, diphasic waves

with enhanced negativity at points immediately preceding the

block, and initial-positive waves alone or abolition of any

wave at points beyond the block. The absence of their

terminal-positive phases paradoxically enhanced the negative

peak of the spinal SSEPs in a partial block that involved only

the constituent fastest fibers, because phase cancellation of

the phases between the terminal-positive phases of the

fastest fibers and the negative phases of the slower fibers,

which normally happens, failed to occur. At the points

immediately preceding the block, the identical mechanism

sustained the spinal SSEP enhancement even when every fiber

was included in the block. The computer model predicted that

localization of the precise site of conduction block can be

achieved by demonstrating an abrupt reduction in the

amplitude of the spinal SSEP, which is accompanied by an

increased negative wave caudally and an enhanced monophasic

positive wave rostrally.

448. Tani, T.; Ushida, T.; Yamamoto, H.; Okuhara, Y. Waveform changes

due to conduction block and their underlying mechanism in

spinal somatosensory evoked potential: a computer simulation.

Technical note. J-Neurosurg. 1997 Feb; 86(2): 303-10; ISSN:

0022-3085.

UNITED-STATES. Based on a square-wave solid-angle analysis,

a simplified mathematical model was produced for computing

a sequence of potential change in a volume conductor

generated by an impulse traveling along a nerve fiber. A

conduction block was simulated as a phenomenon in which a

depolarization wavefront stops traveling when it reaches a

certain point, although the following repolarization wavefront

continues to travel until it reaches the same point. The spinal

somatosensory evoked potential (SSEP) was produced as an

algebraic sum of simulated nerve fiber action potentials

(NFAPs). With a conduction block, an NFAP that was normally

triphasic showed a positive-negative diphasic wave with

reduced negativity at the point of the block, diphasic waves

with enhanced negativity at points immediately preceding the

block, and initial-positive waves alone or abolition of any

wave at points beyond the block. The absence of their

terminal-positive phases paradoxically enhanced the negative

peak of the spinal SSEPs in a partial block that involved only

the constituent fastest fibers, because phase cancellation of

the phases between the terminal-positive phases of the

fastest fibers and the negative phases of the slower fibers,

which normally happens, failed to occur. At the points

immediately preceding the block, the identical mechanism

sustained the spinal SSEP enhancement even when every fiber

was included in the block. The computer model predicted that

localization of the precise site of conduction block can be

achieved by demonstrating an abrupt reduction in the

amplitude of the spinal SSEP, which is accompanied by an

increased negative wave caudally and an enhanced monophasic

positive wave rostrally.

449. Tantisira, B.; Alstermark, B.; Isa, T.; Kummel, H.; Pinter, M.

Motoneuronal projection pattern of single C3-C4 propriospinal

neurones. Can-J-Physiol-Pharmacol. 1996 Apr; 74(4): 518-30;

ISSN: 0008-4212.

CANADA. The pattern of motoneuronal projection and

termination of single C3-C4 propriospinal neurones in the

forelimb segments C6-T1 of the cat was investigated by

intra-axonal injection of horseradish peroxidase into stem

axons. Twelve well-stained axons were used for analysis.

Termination was observed in the estimated location of motor

nuclei innervating pure shoulder muscles in 10 cases. Among

motoneurones innervating shoulder, elbow, wrist, and digit

muscles, projection and termination were observed in motor

nuclei controlling muscles of two or three joints in the

following combinations: shoulder + elbow, shoulder + wrist,

shoulder + elbow + wrist, shoulder + elbow + digit, and elbow +

wrist + digit. In one case it was difficult to exclude the

possibility of projection and termination in motor nuclei

controlling muscles at all four joints. These patterns of

motoneuronal projection from C3-C4 propriospinal neurones

are compatible with their function in mediating the descending

command for visually guided target reaching movements with

the forelimb. In addition, it was found that the C3-C4

propriospinal neurones project and terminate in the region of

ventral and ventromedial motor nuclei, which innervate axial

muscles acting on the trunk. This was confirmed by

intracellular recording from presumed ventromedial

motoneurones in the C6-C7 segments. It is postulated that the

C3-C4 propriospinal neurones, in addition to their control of

forelimb movements, provide for conjoint control of axial

muscles to stabilize the trunk during target reaching.. EC

1.11.1.-.

450. Tantisira, B.; Alstermark, B.; Isa, T.; Kummel, H.; Pinter, M.

Motoneuronal projection pattern of single C3-C4 propriospinal

neurones. Can-J-Physiol-Pharmacol. 1996 Apr; 74(4): 518-30;

ISSN: 0008-4212.

CANADA. The pattern of motoneuronal projection and

termination of single C3-C4 propriospinal neurones in the

forelimb segments C6-T1 of the cat was investigated by

intra-axonal injection of horseradish peroxidase into stem

axons. Twelve well-stained axons were used for analysis.

Termination was observed in the estimated location of motor

nuclei innervating pure shoulder muscles in 10 cases. Among

motoneurones innervating shoulder, elbow, wrist, and digit

muscles, projection and termination were observed in motor

nuclei controlling muscles of two or three joints in the

following combinations: shoulder + elbow, shoulder + wrist,

shoulder + elbow + wrist, shoulder + elbow + digit, and elbow +

wrist + digit. In one case it was difficult to exclude the

possibility of projection and termination in motor nuclei

controlling muscles at all four joints. These patterns of

motoneuronal projection from C3-C4 propriospinal neurones

are compatible with their function in mediating the descending

command for visually guided target reaching movements with

the forelimb. In addition, it was found that the C3-C4

propriospinal neurones project and terminate in the region of

ventral and ventromedial motor nuclei, which innervate axial

muscles acting on the trunk. This was confirmed by

intracellular recording from presumed ventromedial

motoneurones in the C6-C7 segments. It is postulated that the

C3-C4 propriospinal neurones, in addition to their control of

forelimb movements, provide for conjoint control of axial

muscles to stabilize the trunk during target reaching.. EC

1.11.1.-.

451. Tekavcic, I.; Smrkolj, V. A. The path of a wounding missile along

the spinal canal: a case report. Spine. 1996 Mar 1; 21(5): 639-

41; ISSN: 0362-2436.

UNITED-STATES. STUDY DESIGN: The authors report a

penetrating gunshot injury to the cervical spine at the C6

level, with retention of the missile within the spinal canal at

the T10 level. OBJECTIVES: The treatment of this patient

involved debridement of entrance wound on the day of

admission and laminectomies in the cervical and thoracic

levels 3 days after the incident. SUMMARY OF BACKGROUND

DATA: The migration of a foreign body along the intracranial

part of the central nervous system has been reported in the

literature, but we have found no report of an intercanal

gunshot wound measuring 30 cm with complete liquefaction of

the cord. METHODS: On admission, a 21-year-old man had an

entrance wound on the right side of neck. He had complete

paraplegia and could not flex the wrist. The cervical spine

radiograph revealed a fracture of the C5 arch and metallic

fragments in the spinal canal. A radiograph of the thoracic and

lumbar spine disclosed a bullet trapped at the T10 level.

Laminectomies at C6-C7 and T9-T10 were performed and the

bullet and its fragments were removed. The ruptured dura was

replaced by lyophilized dura. RESULTS: The wounds healed

without infection. On discharges the patient's neurologic

status was unchanged. CONCLUSIONS: Laminectomies and

removal of metallic foreign bodies were performed to reduce

the risk of infection in the spinal canal and to prevent toxic

effects of dissolved metals on uninjured parts of the central

nervous system.. 31112-62-6.

452. Tekavcic, I.; Smrkolj, V. A. The path of a wounding missile along

the spinal canal: a case report. Spine. 1996 Mar 1; 21(5): 639-

41; ISSN: 0362-2436.

UNITED-STATES. STUDY DESIGN: The authors report a

penetrating gunshot injury to the cervical spine at the C6

level, with retention of the missile within the spinal canal at

the T10 level. OBJECTIVES: The treatment of this patient

involved debridement of entrance wound on the day of

admission and laminectomies in the cervical and thoracic

levels 3 days after the incident. SUMMARY OF BACKGROUND

DATA: The migration of a foreign body along the intracranial

part of the central nervous system has been reported in the

literature, but we have found no report of an intercanal

gunshot wound measuring 30 cm with complete liquefaction of

the cord. METHODS: On admission, a 21-year-old man had an

entrance wound on the right side of neck. He had complete

paraplegia and could not flex the wrist. The cervical spine

radiograph revealed a fracture of the C5 arch and metallic

fragments in the spinal canal. A radiograph of the thoracic and

lumbar spine disclosed a bullet trapped at the T10 level.

Laminectomies at C6-C7 and T9-T10 were performed and the

bullet and its fragments were removed. The ruptured dura was

replaced by lyophilized dura. RESULTS: The wounds healed

without infection. On discharges the patient's neurologic

status was unchanged. CONCLUSIONS: Laminectomies and

removal of metallic foreign bodies were performed to reduce

the risk of infection in the spinal canal and to prevent toxic

effects of dissolved metals on uninjured parts of the central

nervous system.. 31112-62-6.

453. Teoh, H.; Malcangio, M.; Fowler, L. J.; Bowery, N. G. Evidence for

release of glutamic acid, aspartic acid and substance P but not

gamma-aminobutyric acid from primary afferent fibres in rat

spinal cord. Eur-J-Pharmacol. 1996 Apr 29; 302(1-3): 27-36;

ISSN: 0014-2999.

NETHERLANDS. In vitro superfusion release experiments and

autoradiography were carried out on spinal cords of neonatally

capsaicin-treated rats. Electrical and chemical stimulations

significantly increased the release of aspartate, glutamate

and gamma-aminobutyric acid (GABA) from hemisected dorsal

horn slices of vehicle-treated animals. In capsaicin-treated

rats, the evoked release of aspartate, glutamate and substance

P but not GABA, were significantly lower. Capsaicin (1

microM) stimulated the release of aspartate and glutamate, as

reported for substance P, in control slices but this effect was

not as apparent in tissues from capsaicin-treated rats. Evoked

GABA release was not affected in either case. alpha-Amino-3-

hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate,

dizocilpine and GABAB binding sites were highly localised in

the substantia gelatinosa. Capsaicin treatment did not affect

the affinity of the binding sites in all four cases but

significantly reduced the density of kainate, dizocilpine and

GABAB binding sites. The data suggest that capsaicin-

sensitive primary afferent fibres release aspartate, glutamate

and Substance P following high-intensity stimulations and

that this release might be modulated by presynaptic glutamate

and GABAB receptors present on these terminals.. 0; 33507-

63-0; 404-86-4; 56-12-2; 56-84-8; 56-86-0.

454. Teoh, H.; Malcangio, M.; Fowler, L. J.; Bowery, N. G. Evidence for

release of glutamic acid, aspartic acid and substance P but not

gamma-aminobutyric acid from primary afferent fibres in rat

spinal cord. Eur-J-Pharmacol. 1996 Apr 29; 302(1-3): 27-36;

ISSN: 0014-2999.

NETHERLANDS. In vitro superfusion release experiments and

autoradiography were carried out on spinal cords of neonatally

capsaicin-treated rats. Electrical and chemical stimulations

significantly increased the release of aspartate, glutamate

and gamma-aminobutyric acid (GABA) from hemisected dorsal

horn slices of vehicle-treated animals. In capsaicin-treated

rats, the evoked release of aspartate, glutamate and substance

P but not GABA, were significantly lower. Capsaicin (1

microM) stimulated the release of aspartate and glutamate, as

reported for substance P, in control slices but this effect was

not as apparent in tissues from capsaicin-treated rats. Evoked

GABA release was not affected in either case. alpha-Amino-3-

hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate,

dizocilpine and GABAB binding sites were highly localised in

the substantia gelatinosa. Capsaicin treatment did not affect

the affinity of the binding sites in all four cases but

significantly reduced the density of kainate, dizocilpine and

GABAB binding sites. The data suggest that capsaicin-

sensitive primary afferent fibres release aspartate, glutamate

and Substance P following high-intensity stimulations and

that this release might be modulated by presynaptic glutamate

and GABAB receptors present on these terminals.. 0; 33507-

63-0; 404-86-4; 56-12-2; 56-84-8; 56-86-0.

455. Terao, S.; Sobue, G.; Hashizume, Y.; Li, M.; Inagaki, T.; Mitsuma, T.

Age-related changes in human spinal ventral horn cells with

special reference to the loss of small neurons in the

intermediate zone: a quantitative analysis. Acta-Neuropathol-

Berl. 1996 Aug; 92(2): 109-14; ISSN: 0001-6322.

GERMANY. A cytoarchitectonic study of spinal ventral horn

cells was performed to identify age-related changes. The

diameter distribution of ventral horn neurons of the fourth

lumbar segment of the spinal cord and their size and

topographical distributions were investigated in 14 autopsy

cases. These cases represented patients of 18-100 years of

age who had died of non-neurological diseases. The results

indicate that small neurons widely distributed in the

intermediate zone of the ventral horn significantly diminished

with aging (P < 0.0005, r = -0.898), whereas medium-sized and

large neurons located in the medial and lateral nuclei showed

only a slight decrease with advancing age. The total number of

neurons in the whole ventral horn was also noted to decrease

significantly with aging (P < 0.0005, r = -0.899). While small

neurons in the intermediate zone of the ventral horn are

thought to be mostly interneurons, their physiological function

still remains obscure in many respects. The findings of this

study provide insight into age-related cell loss in terms of

size and location.

456. Terao, S.; Sobue, G.; Hashizume, Y.; Li, M.; Inagaki, T.; Mitsuma, T.

Age-related changes in human spinal ventral horn cells with

special reference to the loss of small neurons in the

intermediate zone: a quantitative analysis. Acta-Neuropathol-

Berl. 1996 Aug; 92(2): 109-14; ISSN: 0001-6322.

GERMANY. A cytoarchitectonic study of spinal ventral horn

cells was performed to identify age-related changes. The

diameter distribution of ventral horn neurons of the fourth

lumbar segment of the spinal cord and their size and

topographical distributions were investigated in 14 autopsy

cases. These cases represented patients of 18-100 years of

age who had died of non-neurological diseases. The results

indicate that small neurons widely distributed in the

intermediate zone of the ventral horn significantly diminished

with aging (P < 0.0005, r = -0.898), whereas medium-sized and

large neurons located in the medial and lateral nuclei showed

only a slight decrease with advancing age. The total number of

neurons in the whole ventral horn was also noted to decrease

significantly with aging (P < 0.0005, r = -0.899). While small

neurons in the intermediate zone of the ventral horn are

thought to be mostly interneurons, their physiological function

still remains obscure in many respects. The findings of this

study provide insight into age-related cell loss in terms of

size and location.

457. Thomson, D. B.; Ikegami, H.; Wilson, V. J. Effect of MLF transection

on the vertical vestibulocollic reflex in decerebrate cats. J-

Neurophysiol. 1995 Oct; 74(4): 1815-8; ISSN: 0022-3077.

UNITED-STATES. 1. In the cat, motoneurons supplying biventer

cervicis, complexus and rectus capitis posterior receive

disynaptic input from the posterior semicircular canals and

from the contralateral anterior canal via the medial

vestibulospinal tract (MVST). Disynaptic excitation from the

ipsilateral anterior canal reaches these motoneurons via the

lateral vestibulospinal tract. 2. We hypothesized that if the

MVST has a unique role in the production of the vertical

vestibulocollic reflex (VCR) in these muscles then interruption

of this tract by transection of the medial longitudinal

fasciculus (MLF) would change the VCR responses. Specifically,

response vector orientations would shift toward the plane of

the ipsilateral anterior canal, and response gains would drop

at high frequencies. 3. We lesioned the MLF bilaterally and

observed no substantial effect on neck-muscle responses.

Response vector orientations did not shift systematically

toward a single plane, nor was there a consistent decrease in

response gains at high frequencies. 4. As in the horizontal VCR,

there is no unique contribution from MVST neurons; parallel

pathways must play an important role in the vertical VCR.

458. Thomson, D. B.; Ikegami, H.; Wilson, V. J. Effect of MLF transection

on the vertical vestibulocollic reflex in decerebrate cats. J-

Neurophysiol. 1995 Oct; 74(4): 1815-8; ISSN: 0022-3077.

UNITED-STATES. 1. In the cat, motoneurons supplying biventer

cervicis, complexus and rectus capitis posterior receive

disynaptic input from the posterior semicircular canals and

from the contralateral anterior canal via the medial

vestibulospinal tract (MVST). Disynaptic excitation from the

ipsilateral anterior canal reaches these motoneurons via the

lateral vestibulospinal tract. 2. We hypothesized that if the

MVST has a unique role in the production of the vertical

vestibulocollic reflex (VCR) in these muscles then interruption

of this tract by transection of the medial longitudinal

fasciculus (MLF) would change the VCR responses. Specifically,

response vector orientations would shift toward the plane of

the ipsilateral anterior canal, and response gains would drop

at high frequencies. 3. We lesioned the MLF bilaterally and

observed no substantial effect on neck-muscle responses.

Response vector orientations did not shift systematically

toward a single plane, nor was there a consistent decrease in

response gains at high frequencies. 4. As in the horizontal VCR,

there is no unique contribution from MVST neurons; parallel

pathways must play an important role in the vertical VCR.

459. Tian, G. F.; Duffin, J. Spinal connections of ventral-group

bulbospinal inspiratory neurons studied with cross-correlation

in the decerebrate rat. Exp-Brain-Res. 1996 Sep; 111(2): 178-

86; ISSN: 0014-4819.

GERMANY. We examined the synaptic connections from

ventral-group bulbospinal inspiratory neurons to upper-

cervical inspiratory neurons and phrenic and intercostal

motoneurons in decerebrate rats using cross-correlation.

Inspiratory neurons were recorded in the medulla (n = 28) at

the level of the obex and from the upper-cervical segments (C1

and C2) of the spinal cord (n = 29) in 18 vagotomized,

paralyzed, ventilated, and decerebrated rats. The neurons were

identified by their inspiratory firing pattern and antidromic

activation from the spinal cord at C7. Whole-nerve recordings

were made using bipolar electrodes from the central cut ends

of the C5 phrenic nerve and the external and internal

intercostal nerves at various thoracic levels. Cross-

correlation histograms were computed between these

recordings to detect short time scale synchronizations

indicative of synaptic connections. Cross-correlation

histograms (n = 20), computed between the activities of

ventral-group bulbospinal inspiratory neurons and the phrenic

nerve, all showed peaks (mean half-amplitude width +/- SD,

1.1 +/- 0.3 ms) at short latencies (mean latency +/- SD, 2.0

+/- 0.6 ms) suggestive of monosynaptic excitation. Cross-

correlation histograms (n = 33), computed between the

activities of ventral-group bulbospinal inspiratory neurons and

upper-cervical inspiratory neurons, displayed four (12%) peaks

(mean half-amplitude width +/- SD, 0.9 +/- 0.1 ms) at short

latencies (mean latency +/- SD, 1.8 +/- 0.6 ms) suggestive of

monosynaptic excitation, and six (18%) peaks (mean half-

amplitude width +/- SD, 1.4 +/- 0.4 ms) at latencies near zero

suggestive of excitation from a common source. Cross-

correlation histograms (n = 34), computed between the

activities of ventral-group bulbospinal inspiratory neurons and

the internal and external intercostal nerves at various

thoracic levels (T2-8), showed six (18%) peaks (mean half-

amplitude width +/- SD, 2.5 +/- 0.5 ms) at short latency (mean

latency +/- SD, 4.5 +/- 1.1 ms) suggestive of oligosynaptic

connections. Cross-correlation histograms (n = 42) computed

between activities of intercostal nerves at various levels of

the thoracic spinal cord showed central peaks suggestive of

excitation from a common source. Although the size of the

peaks decreased with segmental separation, the displacement

of the peaks from time zero did not increase with segmental

separation (mean displacement +/- SD, 0.6 +/- 0.6 ms) as

would be expected if the common excitation resulted from a

descending monosynaptic excitation by a source such as the

ventral-group bulbospinal inspiratory neurons. We conclude

that all ventral-group bulbospinal inspiratory neurons make

monosynaptic connections to phrenic motoneurons, a few make

monosynaptic connections to upper-cervical, inspiratory

neurons, but connections to intercostal motoneurons are made

via interneurons.

460. Tian, G. F.; Duffin, J. Spinal connections of ventral-group

bulbospinal inspiratory neurons studied with cross-correlation

in the decerebrate rat. Exp-Brain-Res. 1996 Sep; 111(2): 178-

86; ISSN: 0014-4819.

GERMANY. We examined the synaptic connections from

ventral-group bulbospinal inspiratory neurons to upper-

cervical inspiratory neurons and phrenic and intercostal

motoneurons in decerebrate rats using cross-correlation.

Inspiratory neurons were recorded in the medulla (n = 28) at

the level of the obex and from the upper-cervical segments (C1

and C2) of the spinal cord (n = 29) in 18 vagotomized,

paralyzed, ventilated, and decerebrated rats. The neurons were

identified by their inspiratory firing pattern and antidromic

activation from the spinal cord at C7. Whole-nerve recordings

were made using bipolar electrodes from the central cut ends

of the C5 phrenic nerve and the external and internal

intercostal nerves at various thoracic levels. Cross-

correlation histograms were computed between these

recordings to detect short time scale synchronizations

indicative of synaptic connections. Cross-correlation

histograms (n = 20), computed between the activities of

ventral-group bulbospinal inspiratory neurons and the phrenic

nerve, all showed peaks (mean half-amplitude width +/- SD,

1.1 +/- 0.3 ms) at short latencies (mean latency +/- SD, 2.0

+/- 0.6 ms) suggestive of monosynaptic excitation. Cross-

correlation histograms (n = 33), computed between the

activities of ventral-group bulbospinal inspiratory neurons and

upper-cervical inspiratory neurons, displayed four (12%) peaks

(mean half-amplitude width +/- SD, 0.9 +/- 0.1 ms) at short

latencies (mean latency +/- SD, 1.8 +/- 0.6 ms) suggestive of

monosynaptic excitation, and six (18%) peaks (mean half-

amplitude width +/- SD, 1.4 +/- 0.4 ms) at latencies near zero

suggestive of excitation from a common source. Cross-

correlation histograms (n = 34), computed between the

activities of ventral-group bulbospinal inspiratory neurons and

the internal and external intercostal nerves at various

thoracic levels (T2-8), showed six (18%) peaks (mean half-

amplitude width +/- SD, 2.5 +/- 0.5 ms) at short latency (mean

latency +/- SD, 4.5 +/- 1.1 ms) suggestive of oligosynaptic

connections. Cross-correlation histograms (n = 42) computed

between activities of intercostal nerves at various levels of

the thoracic spinal cord showed central peaks suggestive of

excitation from a common source. Although the size of the

peaks decreased with segmental separation, the displacement

of the peaks from time zero did not increase with segmental

separation (mean displacement +/- SD, 0.6 +/- 0.6 ms) as

would be expected if the common excitation resulted from a

descending monosynaptic excitation by a source such as the

ventral-group bulbospinal inspiratory neurons. We conclude

that all ventral-group bulbospinal inspiratory neurons make

monosynaptic connections to phrenic motoneurons, a few make

monosynaptic connections to upper-cervical, inspiratory

neurons, but connections to intercostal motoneurons are made

via interneurons.

461. Tortori Donati, P.; Fondelli, M. P.; Rossi, A.; Andreussi, L.;

Brisigotti, M.; Garre, M. L. MRI in an unusual case of congenital

spinal mesenchymal proliferation. Neuroradiology. 1996 May;

38 Suppl 1: S196-9; ISSN: 0028-3940.

GERMANY. We report a child aged 2 years presenting with

delayed motor development. A thoracolumbar subcutaneous

mass was noticed in the first months of life. MRI showed a low

conus medullaris, confirmed the presence of the mass and

detected a second solid lesion in the intradural space. Surgery

confirmed that the two lesions were distinct, as on MRI. The

histopathological features were in common with fibrous

hamartoma of infancy, giant cell angioblastoma and the

"diffuse type" of infantile fibromatosis. The presence of a low

conus medullaris associated with a congenital clinical

presentation suggested a disontogenetic aetiology.

462. Tortori Donati, P.; Fondelli, M. P.; Rossi, A.; Andreussi, L.;

Brisigotti, M.; Garre, M. L. MRI in an unusual case of congenital

spinal mesenchymal proliferation. Neuroradiology. 1996 May;

38 Suppl 1: S196-9; ISSN: 0028-3940.

GERMANY. We report a child aged 2 years presenting with

delayed motor development. A thoracolumbar subcutaneous

mass was noticed in the first months of life. MRI showed a low

conus medullaris, confirmed the presence of the mass and

detected a second solid lesion in the intradural space. Surgery

confirmed that the two lesions were distinct, as on MRI. The

histopathological features were in common with fibrous

hamartoma of infancy, giant cell angioblastoma and the

"diffuse type" of infantile fibromatosis. The presence of a low

conus medullaris associated with a congenital clinical

presentation suggested a disontogenetic aetiology.

463. Traub, R. J.; Sengupta, J. N.; Gebhart, G. F. Differential c-fos

expression in the nucleus of the solitary tract and spinal cord

following noxious gastric distention in the rat. Neuroscience.

1996 Oct; 74(3): 873-84; ISSN: 0306-4522.

UNITED-STATES. c-Fos has been used as a marker for activity

in the spinal cord following noxious somatic or visceral

stimulation. Although the viscera receive dual afferent

innervation, distention of hollow organs (i.e. esophagus,

stomach, descending colon and rectum) induces significantly

more c-Fos in second order neurons in the nucleus of the

solitary tract and lumbosacral spinal cord, which receive

parasympathetic afferent input (vagus, pelvic nerves), than the

thoracolumbar spinal cord, which receives sympathetic

afferent input (splanchnic nerves). The purpose of this study

was to determine the contribution of sympathetic and

parasympathetic afferent input to c-Fos expression in the

nucleus of the solitary tract and spinal cord, and the influence

of supraspinal pathways on Fos induction in the thoracolumbar

spinal cord. Noxious gastric distention to 80 mmHg (gastric

distension/80) was produced by repetitive inflation of a

chronically implanted gastric balloon. Gastric distension/80

induced c-Fos throughout the nucleus of the solitary tract,

with the densest labeling observed within 300 microns of the

rostral pole of the area postrema. This area was analysed

quantitatively following several manipulations. Gastric

distension/80 induced a mean of 724 c-Fos-immunoreactive

nuclei per section. Following subdiaphragmatic vagotomy plus

distention (vagotomy/80), the induction of c-Fos-

immunoreactive nuclei was reduced to 293 per section, while

spinal transection at T2 plus distention (spinal

transection/80) induced a mean of 581 nuclei per nucleus of

the solitary tract section. Gastric distension/80 and

vagotomy/80 induced minimal c-Fos in the T8-T10 spinal cord

(50 nuclei/section), but spinal transection/80 induced 200

nuclei per section. Repetitive bolus injections of

norepinephrine produced transient pressor responses

mimicking the pressor response produced by gastric

distension/80. This manipulation induced minimal c-Fos in the

nucleus of the solitary tract and none in the spinal cord. It is

concluded that noxious visceral input via parasympathetic

vagal afferents, and to a lesser extent sympathetic afferents

and the spinosolitary tract, contribute to gastric distention-

induced c-Fos in the nucleus of the solitary tract. The

induction of c-Fos in the nucleus of the solitary tract is

significantly greater than in the viscerotopic segments of the

spinal cord, which is partially under tonic descending

inhibition, but is not subject to modulation by vagal gastric

afferents. Distention pressures produced by noxious gastric

distention are much greater than those produced during

feeding, suggesting that c-Fos induction in the nucleus of the

solitary tract to noxious distention is not associated with

physiological mechanisms of feeding and satiety. The large

vagal nerve-mediated induction of c-Fos in the nucleus of the

solitary tract following gastric distension suggests that

parasympathetic afferents contribute to the processing of

noxious visceral stimuli, perhaps by contributing to the

affective-emotional component of visceral pain.. 0; 51-41-2.

464. Traub, R. J.; Sengupta, J. N.; Gebhart, G. F. Differential c-fos

expression in the nucleus of the solitary tract and spinal cord

following noxious gastric distention in the rat. Neuroscience.

1996 Oct; 74(3): 873-84; ISSN: 0306-4522.

UNITED-STATES. c-Fos has been used as a marker for activity

in the spinal cord following noxious somatic or visceral

stimulation. Although the viscera receive dual afferent

innervation, distention of hollow organs (i.e. esophagus,

stomach, descending colon and rectum) induces significantly

more c-Fos in second order neurons in the nucleus of the

solitary tract and lumbosacral spinal cord, which receive

parasympathetic afferent input (vagus, pelvic nerves), than the

thoracolumbar spinal cord, which receives sympathetic

afferent input (splanchnic nerves). The purpose of this study

was to determine the contribution of sympathetic and

parasympathetic afferent input to c-Fos expression in the

nucleus of the solitary tract and spinal cord, and the influence

of supraspinal pathways on Fos induction in the thoracolumbar

spinal cord. Noxious gastric distention to 80 mmHg (gastric

distension/80) was produced by repetitive inflation of a

chronically implanted gastric balloon. Gastric distension/80

induced c-Fos throughout the nucleus of the solitary tract,

with the densest labeling observed within 300 microns of the

rostral pole of the area postrema. This area was analysed

quantitatively following several manipulations. Gastric

distension/80 induced a mean of 724 c-Fos-immunoreactive

nuclei per section. Following subdiaphragmatic vagotomy plus

distention (vagotomy/80), the induction of c-Fos-

immunoreactive nuclei was reduced to 293 per section, while

spinal transection at T2 plus distention (spinal

transection/80) induced a mean of 581 nuclei per nucleus of

the solitary tract section. Gastric distension/80 and

vagotomy/80 induced minimal c-Fos in the T8-T10 spinal cord

(50 nuclei/section), but spinal transection/80 induced 200

nuclei per section. Repetitive bolus injections of

norepinephrine produced transient pressor responses

mimicking the pressor response produced by gastric

distension/80. This manipulation induced minimal c-Fos in the

nucleus of the solitary tract and none in the spinal cord. It is

concluded that noxious visceral input via parasympathetic

vagal afferents, and to a lesser extent sympathetic afferents

and the spinosolitary tract, contribute to gastric distention-

induced c-Fos in the nucleus of the solitary tract. The

induction of c-Fos in the nucleus of the solitary tract is

significantly greater than in the viscerotopic segments of the

spinal cord, which is partially under tonic descending

inhibition, but is not subject to modulation by vagal gastric

afferents. Distention pressures produced by noxious gastric

distention are much greater than those produced during

feeding, suggesting that c-Fos induction in the nucleus of the

solitary tract to noxious distention is not associated with

physiological mechanisms of feeding and satiety. The large

vagal nerve-mediated induction of c-Fos in the nucleus of the

solitary tract following gastric distension suggests that

parasympathetic afferents contribute to the processing of

noxious visceral stimuli, perhaps by contributing to the

affective-emotional component of visceral pain.. 0; 51-41-2.

465. Tseng, G. F.; Wang, Y. J.; Hu, M. E. Axotomy affects the retrograde

labeling of cervical and lumbar-cord-projecting rubrospinal

neurons differently. Anat-Embryol-Berl. 1996 Nov; 194(5):

457-64; ISSN: 0340-2061.

GERMANY. The effect of axotomy at cervical and lumbar spinal

levels upon the ability of rubrospinal neurons to retrogradely

transport tracer was compared. Unilateral rubrospinal

tractotomy was performed first at C5 and, after a few days, at

C2 vertebral levels. Different retrograde tracers were applied

at the lesioned sites right after tractotomy. Tracer applied at

C5 labeled both cervical and lumbar-cord-projecting neurons.

Tracer applied at C2 also labeled both groups of neurons if

performed 2 days after that at C5; however, only cervical-

cord-projecting neurons were labeled when it was performed 3

or 5 days after that at C5. In another set of experiments, a T10

tractotomy without tracer application was performed 2 or 5

days prior to the C5/C2, series of tract lesions. When preceded

by a T10 lesion 2 days in advance, tracer applied at C5 labeled

both cervical and lumbar-cord-projecting neurons. However, a

T10 lesion 5 days in advance resulted in the labeling of only

cervical-cord-projecting neurons by the tracer applied at C5.

In either case, tracer applied at C2 consistently labeled only

cervical-cord-projecting neurons, irrespective of the

intervals-2, 3, or 5 days-allowed between C5 and C2 lesions.

Most neurons labeled from C2 were also double-labeled by the

tracer applied at C5. Thus, unlike lumbar-cord-projecting

counterparts, cervical-cord-projecting rubrospinal neurons

retain the ability to uptake and/or transport retrograde tracer

several days following axotomy. This implies that cervical-

cord-projecting rubrospinal neurons survive in a different

functional state from their lumbar-cord-projecting

counterparts following axonal injury.

466. Tseng, G. F.; Wang, Y. J.; Hu, M. E. Axotomy affects the retrograde

labeling of cervical and lumbar-cord-projecting rubrospinal

neurons differently. Anat-Embryol-Berl. 1996 Nov; 194(5):

457-64; ISSN: 0340-2061.

GERMANY. The effect of axotomy at cervical and lumbar spinal

levels upon the ability of rubrospinal neurons to retrogradely

transport tracer was compared. Unilateral rubrospinal

tractotomy was performed first at C5 and, after a few days, at

C2 vertebral levels. Different retrograde tracers were applied

at the lesioned sites right after tractotomy. Tracer applied at

C5 labeled both cervical and lumbar-cord-projecting neurons.

Tracer applied at C2 also labeled both groups of neurons if

performed 2 days after that at C5; however, only cervical-

cord-projecting neurons were labeled when it was performed 3

or 5 days after that at C5. In another set of experiments, a T10

tractotomy without tracer application was performed 2 or 5

days prior to the C5/C2, series of tract lesions. When preceded

by a T10 lesion 2 days in advance, tracer applied at C5 labeled

both cervical and lumbar-cord-projecting neurons. However, a

T10 lesion 5 days in advance resulted in the labeling of only

cervical-cord-projecting neurons by the tracer applied at C5.

In either case, tracer applied at C2 consistently labeled only

cervical-cord-projecting neurons, irrespective of the

intervals-2, 3, or 5 days-allowed between C5 and C2 lesions.

Most neurons labeled from C2 were also double-labeled by the

tracer applied at C5. Thus, unlike lumbar-cord-projecting

counterparts, cervical-cord-projecting rubrospinal neurons

retain the ability to uptake and/or transport retrograde tracer

several days following axotomy. This implies that cervical-

cord-projecting rubrospinal neurons survive in a different

functional state from their lumbar-cord-projecting

counterparts following axonal injury.

467. Tseng, G. F.; Wang, Y. J.; Lai, Q. C. Perineuronal microglial

reactivity following proximal and distal axotomy of rat

rubrospinal neurons. Brain-Res. 1996 Apr 9; 715(1-2): 32-43;

ISSN: 0006-8993.

NETHERLANDS. Microglial reactivity in the red nucleus of rats

was studied following upper cervical and lower thoracic

rubrospinal tractotomy using the lectin binding method.

Following axotomy, the contralateral nucleus containing the

axotomized neurons was identified using the retrograde tracer

Fast blue. It was subdivided into dorsomedial (DM) and

ventrolateral (VL) portions known to project to the cervical

and lumbar spinal cord, respectively. Lectin-labeled microglial

cells and processes on the contralateral as well as in the

ipsilateral nucleus were then quantified. An early and a late

increase in microglial reactivity was observed in the nucleus

at 2-5 days and 2-8 weeks following thoracic and cervical

tractotomy with the latter producing a more pronounced

reactivity. In rats subjected to thoracic axotomy, a similar

microglial increase also occurred in the intact contralateral

DM nuclear area suggesting the possible action of diffusable

factor(s) that might have triggered the microglial activation

from the axotomized VL nuclear area. The uninjured ipsilateral

nucleus also exhibited a similar pattern of microglial

reactivity irrespective of the number of ipsilaterally

projecting neurons following both cervical and thoracic

axotomy. This could have been elicited by the retrograde

influence from the denervated targets carried by the intact

rubrospinal fibers of the opposite side since many of them in

fact terminate bilaterally (Antal, M. et al., J. Comp. Neurol.,

325 (1992) 22-37). In all the axotomized or intact nucleus,

microglial processes did not appear to surround neuronal cell

bodies. The characteristic responses of microglial cells in the

red nucleus may be related to the failure of rubrospinal

neurons to regenerate following the severance of their axons..

0; 0; 0; 0; 74749-42-1.

468. Tseng, G. F.; Wang, Y. J.; Lai, Q. C. Perineuronal microglial

reactivity following proximal and distal axotomy of rat

rubrospinal neurons. Brain-Res. 1996 Apr 9; 715(1-2): 32-43;

ISSN: 0006-8993.

NETHERLANDS. Microglial reactivity in the red nucleus of rats

was studied following upper cervical and lower thoracic

rubrospinal tractotomy using the lectin binding method.

Following axotomy, the contralateral nucleus containing the

axotomized neurons was identified using the retrograde tracer

Fast blue. It was subdivided into dorsomedial (DM) and

ventrolateral (VL) portions known to project to the cervical

and lumbar spinal cord, respectively. Lectin-labeled microglial

cells and processes on the contralateral as well as in the

ipsilateral nucleus were then quantified. An early and a late

increase in microglial reactivity was observed in the nucleus

at 2-5 days and 2-8 weeks following thoracic and cervical

tractotomy with the latter producing a more pronounced

reactivity. In rats subjected to thoracic axotomy, a similar

microglial increase also occurred in the intact contralateral

DM nuclear area suggesting the possible action of diffusable

factor(s) that might have triggered the microglial activation

from the axotomized VL nuclear area. The uninjured ipsilateral

nucleus also exhibited a similar pattern of microglial

reactivity irrespective of the number of ipsilaterally

projecting neurons following both cervical and thoracic

axotomy. This could have been elicited by the retrograde

influence from the denervated targets carried by the intact

rubrospinal fibers of the opposite side since many of them in

fact terminate bilaterally (Antal, M. et al., J. Comp. Neurol.,

325 (1992) 22-37). In all the axotomized or intact nucleus,

microglial processes did not appear to surround neuronal cell

bodies. The characteristic responses of microglial cells in the

red nucleus may be related to the failure of rubrospinal

neurons to regenerate following the severance of their axons..

0; 0; 0; 0; 74749-42-1.

469. Uematsu, J.; Ono, K.; Yamano, T.; Shimada, M. Development of

corticospinal tract fibers and their plasticity. II. Neonatal

unilateral cortical damage and subsequent development of the

corticospinal tract in mice. Brain-Dev. 1996 May; 18(3): 173-

8; ISSN: 0387-7604.

NETHERLANDS. In this study, the right cerebral cortices of

mice on postnatal day 0 (P0) were cryocoagulated with dry ice.

Subsequent development of the corticospinal tract (CST) was

studied morphologically and quantitatively, and was compared

with that in age-matched controls. When the pyramidal tract

was traced anterogradely by injecting HRP into the

sensorimotor area of the left cerebral cortex of adult operated

mice, the right CST originating from the healthy left

hemisphere showed remarkable hypertrophy. The number of

axons in the CST at the C4-C6 level became maximum on P14

in the control mice and rapidly decreased thereafter. In the

operated mice, the axonal number in the right CST also was

maximal on P14 and then rapidly decreased. However, the

decrease in axonal number after P21 was less in the operated

mice than in the controls. Moreover, the number of axons

showed a slight increase after P56. These results indicate

that the physiological elimination of the parent axons and

their collaterals is much lower in the operated mice than in

the controls, and that the increase in axon collaterals from

parent axons in the hypertrophic right CST persists a long time

in the operated mice.. EC 1.11.1.-.

470. Uematsu, J.; Ono, K.; Yamano, T.; Shimada, M. Development of

corticospinal tract fibers and their plasticity. II. Neonatal

unilateral cortical damage and subsequent development of the

corticospinal tract in mice. Brain-Dev. 1996 May; 18(3): 173-

8; ISSN: 0387-7604.

NETHERLANDS. In this study, the right cerebral cortices of

mice on postnatal day 0 (P0) were cryocoagulated with dry ice.

Subsequent development of the corticospinal tract (CST) was

studied morphologically and quantitatively, and was compared

with that in age-matched controls. When the pyramidal tract

was traced anterogradely by injecting HRP into the

sensorimotor area of the left cerebral cortex of adult operated

mice, the right CST originating from the healthy left

hemisphere showed remarkable hypertrophy. The number of

axons in the CST at the C4-C6 level became maximum on P14

in the control mice and rapidly decreased thereafter. In the

operated mice, the axonal number in the right CST also was

maximal on P14 and then rapidly decreased. However, the

decrease in axonal number after P21 was less in the operated

mice than in the controls. Moreover, the number of axons

showed a slight increase after P56. These results indicate

that the physiological elimination of the parent axons and

their collaterals is much lower in the operated mice than in

the controls, and that the increase in axon collaterals from

parent axons in the hypertrophic right CST persists a long time

in the operated mice.. EC 1.11.1.-.

471. Unsinn, K. M.; Mader, R.; Gassner, I.; Kreczy, A. Ventriculus

terminalis of the spinal cord in the neonate: a normal variant

on sonography [letter]. AJR-Am-J-Roentgenol. 1996 Nov;

167(5): 1341; ISSN: 0361-803X.

UNITED-STATES.

472. Unsinn, K. M.; Mader, R.; Gassner, I.; Kreczy, A. Ventriculus

terminalis of the spinal cord in the neonate: a normal variant

on sonography [letter]. AJR-Am-J-Roentgenol. 1996 Nov;

167(5): 1341; ISSN: 0361-803X.

UNITED-STATES.

473. Urban, M. O.; Jiang, M. C.; Gebhart, G. F. Participation of central

descending nociceptive facilitatory systems in secondary

hyperalgesia produced by mustard oil. Brain-Res. 1996 Oct 21;

737(1-2): 83-91; ISSN: 0006-8993.

NETHERLANDS. The present series of experiments were

designed to examine a potential role for central descending

pain facilitatory systems in mediating secondary hyperalgesia

produced by topical application of mustard oil and measuring

the nociceptive tail-flick reflex in awake rats. Topical

application of mustard oil (100%) to the lateral surface of the

hind leg produced a facilitation of the tail-flick reflex that

was significantly reduced in spinal transected animals.

Mustard oil hyperalgesia was also inhibited in animals that

had received electrolytic lesions in the rostral ventromedial

medulla (RVM). Intrathecal (i.t.) administration of the non-

selective cholecystokinin (CCK) receptor antagonist

proglumide (10 micrograms) prior to mustard oil application

completely blocked both the lesser and greater hyperalgesic

responses observed in spinal transected and normal animals,

respectively, and produced an inhibition of the tail-flick

reflex in normal animals. Administration of the selective CCKB

receptor antagonist L-365260 i.t. dose-dependently inhibited

mustard oil hyperalgesia (ID50 = 364 ng) at doses

approximately 5-fold less than the CCKA receptor antagonist

devazepide (ID50 = 1760 ng). Similar to spinal proglumide,

microinjection of the neurotensin antagonist SR48692 (3.5

micrograms) into the RVM blocked mustard oil hyperalgesia

and inhibited the tail-flick reflex. These data suggest that

secondary hyperalgesia produced by mustard oil is mediated

largely by a central, centrifugal descending pain facilitatory

system which involves neurotensin in the RVM and spinal CCK

(via CCKB receptors). The inhibition of the tail-flick reflex

produced by mustard oil following spinal or supraspinal

administration of receptor antagonists suggests concurrent

activation of central descending facilitatory and inhibitory

systems.. 0; 0; 0; 0; 0; 0; 0; 0; 103420-77-5; 118101-09-0;

146362-70-1; 39379-15-2; 6620-60-6; 8007-40-7; 9011-

97-6.

474. Urban, M. O.; Jiang, M. C.; Gebhart, G. F. Participation of central

descending nociceptive facilitatory systems in secondary

hyperalgesia produced by mustard oil. Brain-Res. 1996 Oct 21;

737(1-2): 83-91; ISSN: 0006-8993.

NETHERLANDS. The present series of experiments were

designed to examine a potential role for central descending

pain facilitatory systems in mediating secondary hyperalgesia

produced by topical application of mustard oil and measuring

the nociceptive tail-flick reflex in awake rats. Topical

application of mustard oil (100%) to the lateral surface of the

hind leg produced a facilitation of the tail-flick reflex that

was significantly reduced in spinal transected animals.

Mustard oil hyperalgesia was also inhibited in animals that

had received electrolytic lesions in the rostral ventromedial

medulla (RVM). Intrathecal (i.t.) administration of the non-

selective cholecystokinin (CCK) receptor antagonist

proglumide (10 micrograms) prior to mustard oil application

completely blocked both the lesser and greater hyperalgesic

responses observed in spinal transected and normal animals,

respectively, and produced an inhibition of the tail-flick

reflex in normal animals. Administration of the selective CCKB

receptor antagonist L-365260 i.t. dose-dependently inhibited

mustard oil hyperalgesia (ID50 = 364 ng) at doses

approximately 5-fold less than the CCKA receptor antagonist

devazepide (ID50 = 1760 ng). Similar to spinal proglumide,

microinjection of the neurotensin antagonist SR48692 (3.5

micrograms) into the RVM blocked mustard oil hyperalgesia

and inhibited the tail-flick reflex. These data suggest that

secondary hyperalgesia produced by mustard oil is mediated

largely by a central, centrifugal descending pain facilitatory

system which involves neurotensin in the RVM and spinal CCK

(via CCKB receptors). The inhibition of the tail-flick reflex

produced by mustard oil following spinal or supraspinal

administration of receptor antagonists suggests concurrent

activation of central descending facilitatory and inhibitory

systems.. 0; 0; 0; 0; 0; 0; 0; 0; 103420-77-5; 118101-09-0;

146362-70-1; 39379-15-2; 6620-60-6; 8007-40-7; 9011-

97-6.

475. Valentino, R. J.; Chen, S.; Zhu, Y.; Aston Jones, G. Evidence for

divergent projections to the brain noradrenergic system and

the spinal parasympathetic system from Barrington's nucleus.

Brain-Res. 1996 Sep 2; 732(1-2): 1-15; ISSN: 0006-8993.

NETHERLANDS. The present study was designed to determine

whether Barrington's nucleus, which lies ventromedial to the

locus coeruleus (LC) and projects to the sacral

parasympathetic nucleus, is a source of afferent projections

to the LC. Restricted injections of the anterograde tracer,

biocytin, into Barrington's nucleus labeled varicose fibers that

extended from the injection site into the LC. Consistent with

this, injections of the retrograde tracers, wheatgerm

agglutinin conjugated to horseradish peroxidase coupled to

gold particles (WGA-Au-HRP) or fluorescein-conjugated latex

beads, into the LC labeled numerous (approximately 10%)

Barrington's neurons that were also retrogradely labeled by

Fluoro-Gold (FG) injections in the spinal cord. Retrograde

tracing from the LC combined with corticotropin-releasing

hormone (CRH) immunohistochemistry revealed that at least

one third of the retrogradely labeled neurons in Barrington's

nucleus were CRH-immunoreactive (CRH-IR). Finally, in triple

labeling studies, CRH-Barrington's neurons were consistently

observed that were retrogradely labeled from both the and

spinal cord. These findings implicate Barrington's nucleus as

an LC afferent and a source of CRH-IR fibers in the LC.

Additionally, the results suggest that some Barrington's

neurons diverge to innervate both the spinal cord and the LC.

This divergent innervation may serve to coregulate the sacral

parasympathetic nervous system and brain noradrenergic

system, thus providing a mechanism for coordinating pelvic

visceral functions with forebrain activity.. 0; 0; 0; 0; 0; 0;

2321-07-5; 51-41-2; 56-87-1; 576-19-2; 82785-14-6;

9015-71-8.

476. Valentino, R. J.; Chen, S.; Zhu, Y.; Aston Jones, G. Evidence for

divergent projections to the brain noradrenergic system and

the spinal parasympathetic system from Barrington's nucleus.

Brain-Res. 1996 Sep 2; 732(1-2): 1-15; ISSN: 0006-8993.

NETHERLANDS. The present study was designed to determine

whether Barrington's nucleus, which lies ventromedial to the

locus coeruleus (LC) and projects to the sacral

parasympathetic nucleus, is a source of afferent projections

to the LC. Restricted injections of the anterograde tracer,

biocytin, into Barrington's nucleus labeled varicose fibers that

extended from the injection site into the LC. Consistent with

this, injections of the retrograde tracers, wheatgerm

agglutinin conjugated to horseradish peroxidase coupled to

gold particles (WGA-Au-HRP) or fluorescein-conjugated latex

beads, into the LC labeled numerous (approximately 10%)

Barrington's neurons that were also retrogradely labeled by

Fluoro-Gold (FG) injections in the spinal cord. Retrograde

tracing from the LC combined with corticotropin-releasing

hormone (CRH) immunohistochemistry revealed that at least

one third of the retrogradely labeled neurons in Barrington's

nucleus were CRH-immunoreactive (CRH-IR). Finally, in triple

labeling studies, CRH-Barrington's neurons were consistently

observed that were retrogradely labeled from both the and

spinal cord. These findings implicate Barrington's nucleus as

an LC afferent and a source of CRH-IR fibers in the LC.

Additionally, the results suggest that some Barrington's

neurons diverge to innervate both the spinal cord and the LC.

This divergent innervation may serve to coregulate the sacral

parasympathetic nervous system and brain noradrenergic

system, thus providing a mechanism for coordinating pelvic

visceral functions with forebrain activity.. 0; 0; 0; 0; 0; 0;

2321-07-5; 51-41-2; 56-87-1; 576-19-2; 82785-14-6;

9015-71-8.

477. Van, Den Pol AN; Obrietan, K.; Belousov, A. Glutamate

hyperexcitability and seizure-like activity throughout the

brain and spinal cord upon relief from chronic glutamate

receptor blockade in culture. Neuroscience. 1996 Oct; 74(3):

653-74; ISSN: 0306-4522.

UNITED-STATES. Cortical structures such as the hippocampus

and cerebral cortex are considered to be particularly

susceptible to seizure and epileptiform electrical activity

and, as such, are the focus of intense investigation relative to

hyperexcitability.To determine whether parallel glutamate-

mediated hyperexcitability and seizure-like activity in the rat

can be generated by neurons irrespective of their origin within

the CNS, we maintained cells from the spinal

cord,hippocampus, olfactory bulb, striatum, hypothalamus, and

cortex in the long-term presence of glutamate receptor

antagonists 2-amino-5-phosphonovalerate and 6-cyano-7-

nitroquinoxaline-2-3-dione. After removal of chronic (three to

11 weeks) glutamate receptor block, whole-cell patch-clamp

recordings from current-clamped neurons (n = 94) revealed an

immediate increase in large excitatory postsynaptic

potentials and a depolarization of 20-35 mV that was often

sustained for recording periods lasting 5 min (54% of 66

neurons from all six areas). The intense activity was not seen

in age-matched control neurons not subjected to chronic

glutamate receptor block. Selective blockade of ionotropic

glutamate receptors showed that the hyperexcitability was

due to an enhanced response through both AMPA/kainate and N-

methyl-D-aspartate receptors. Relief from chronic glutamate

receptor block also increased inhibitory activity, as revealed

by an increase in inhibitory postsynaptic currents while

neurons were voltage-clamped at -25 mV. These inhibitory

postsynaptic currents could be blocked with bicuculline,

indicating that they were mediated by an enhanced GABA

release. This enhanced GABA activity reduced, but did not

eliminate, the glutamate-mediated hyperactivity, shown by an

increase in both intracellular Ca2+ and excitatory electrical

activity when bicuculline was added. When the glutamate

receptor block was removed, cells (n > 1000) from all six

regions showed exaggerated Ca2+ activity, characterized by

abnormally high increases in intracellular Ca2+, rising from

basal levels of 50-100 nM up to 150-1600 nM. Cd2+ eliminated

the hyperexcitability by blocking Ca2+ channels, and reducing

excitatory transmitter release and response. Fura-2 digital

imaging revealed Ca2+ oscillations with periods ranging from

4 to 60 s. Ca2+ peaks in oscillations in oscillations were

synchronized among most neurons recorded simultaneously.

That synchronization was dependent on a mechanism involving

voltage-dependent Na+ channels was demonstrated with

experiments with tetrodotoxin that blocked Ca2+ rises and

synchronous cellular behavior. Removal of the glutamate

receptor antagonists resulted in the glutamate-mediated death

of 44% of the cells after 23 days of chronic block and 82% cell

death after 40 days of chronic block. Nimodipine substantially

reduced cell death, indicating that one mechanism responsible

for the enhanced cell death after relief from chronic

glutamate receptor block was increased intracellular Ca2+

entry through L-type voltage-gated calcium channels. These

data indicate that glutamate is released by neurons from all

areas studied, including the spinal cord. Sufficient amounts of

glutamate can be released from axon terminals from all areas

to cause cell hippocampal and cortical neurons, but also by

neurons from any of the brain regions tested after chronic

deprivation of glutamate receptor stimulation during

development. This hyperexcitability is mediated by

glutamatergic mechanisms independent of the specific

excitatory connections existing in vivo. The epileptiform

activity of neurons from one region is indistinguishable from

that of another in culture, underlining the importance of

synaptic connections in vivo that define the responses

characteristic of neurons from different brain regions.. 0; 0;

115066-14-3; 4368-28-9; 56-86-0; 7440-43-9; 7440-70-2;

76726-92-6.

478. Van, Den Pol AN; Obrietan, K.; Belousov, A. Glutamate

hyperexcitability and seizure-like activity throughout the

brain and spinal cord upon relief from chronic glutamate

receptor blockade in culture. Neuroscience. 1996 Oct; 74(3):

653-74; ISSN: 0306-4522.

UNITED-STATES. Cortical structures such as the hippocampus

and cerebral cortex are considered to be particularly

susceptible to seizure and epileptiform electrical activity

and, as such, are the focus of intense investigation relative to

hyperexcitability.To determine whether parallel glutamate-

mediated hyperexcitability and seizure-like activity in the rat

can be generated by neurons irrespective of their origin within

the CNS, we maintained cells from the spinal

cord,hippocampus, olfactory bulb, striatum, hypothalamus, and

cortex in the long-term presence of glutamate receptor

antagonists 2-amino-5-phosphonovalerate and 6-cyano-7-

nitroquinoxaline-2-3-dione. After removal of chronic (three to

11 weeks) glutamate receptor block, whole-cell patch-clamp

recordings from current-clamped neurons (n = 94) revealed an

immediate increase in large excitatory postsynaptic

potentials and a depolarization of 20-35 mV that was often

sustained for recording periods lasting 5 min (54% of 66

neurons from all six areas). The intense activity was not seen

in age-matched control neurons not subjected to chronic

glutamate receptor block. Selective blockade of ionotropic

glutamate receptors showed that the hyperexcitability was

due to an enhanced response through both AMPA/kainate and N-

methyl-D-aspartate receptors. Relief from chronic glutamate

receptor block also increased inhibitory activity, as revealed

by an increase in inhibitory postsynaptic currents while

neurons were voltage-clamped at -25 mV. These inhibitory

postsynaptic currents could be blocked with bicuculline,

indicating that they were mediated by an enhanced GABA

release. This enhanced GABA activity reduced, but did not

eliminate, the glutamate-mediated hyperactivity, shown by an

increase in both intracellular Ca2+ and excitatory electrical

activity when bicuculline was added. When the glutamate

receptor block was removed, cells (n > 1000) from all six

regions showed exaggerated Ca2+ activity, characterized by

abnormally high increases in intracellular Ca2+, rising from

basal levels of 50-100 nM up to 150-1600 nM. Cd2+ eliminated

the hyperexcitability by blocking Ca2+ channels, and reducing

excitatory transmitter release and response. Fura-2 digital

imaging revealed Ca2+ oscillations with periods ranging from

4 to 60 s. Ca2+ peaks in oscillations in oscillations were

synchronized among most neurons recorded simultaneously.

That synchronization was dependent on a mechanism involving

voltage-dependent Na+ channels was demonstrated with

experiments with tetrodotoxin that blocked Ca2+ rises and

synchronous cellular behavior. Removal of the glutamate

receptor antagonists resulted in the glutamate-mediated death

of 44% of the cells after 23 days of chronic block and 82% cell

death after 40 days of chronic block. Nimodipine substantially

reduced cell death, indicating that one mechanism responsible

for the enhanced cell death after relief from chronic

glutamate receptor block was increased intracellular Ca2+

entry through L-type voltage-gated calcium channels. These

data indicate that glutamate is released by neurons from all

areas studied, including the spinal cord. Sufficient amounts of

glutamate can be released from axon terminals from all areas

to cause cell hippocampal and cortical neurons, but also by

neurons from any of the brain regions tested after chronic

deprivation of glutamate receptor stimulation during

development. This hyperexcitability is mediated by

glutamatergic mechanisms independent of the specific

excitatory connections existing in vivo. The epileptiform

activity of neurons from one region is indistinguishable from

that of another in culture, underlining the importance of

synaptic connections in vivo that define the responses

characteristic of neurons from different brain regions.. 0; 0;

115066-14-3; 4368-28-9; 56-86-0; 7440-43-9; 7440-70-2;

76726-92-6.

479. Varzin, S. A.; Tikhonova, L. P. [The effect of vagotomy on neuronal

function in different sections of the autonomic nervous

system]. Vliianie vagotomii na sostoianie neironov

razlichnykh otdelov vegetativnoi nervnoi sistemy. Morfologiia.

1996; 110(4): 109-12; ISSN: 0004-1947.

RUSSIA. Neuronal structure was studied during a year after

the truncal subdiaphragmatic two-side vagotomy in nuclei of

vagal nerves and oblongated medulla. Jacobson nuclei in the

spinal cord lateral cornua and stomach and intestinal nerve

plexuses. Dynamics of structural changes in nervous system

different regions after vagotomy was shown. In intramural

nerve ganglionic structure repairs on late post operative

terms, while vagal nerve nuclei in the oblongated medulla

retain significant changes, one of which is the sharp decrease

of neuron number a year after vagotomy. Compensation of

Jacobson nuclei similar to nucl. intermediolateralis was taken

into consideration. So vagotomy is a surgical intervention into

nervous system and into endocrine system associated with it.

480. Varzin, S. A.; Tikhonova, L. P. [The effect of vagotomy on neuronal

function in different sections of the autonomic nervous

system]. Vliianie vagotomii na sostoianie neironov

razlichnykh otdelov vegetativnoi nervnoi sistemy. Morfologiia.

1996; 110(4): 109-12; ISSN: 0004-1947.

RUSSIA. Neuronal structure was studied during a year after

the truncal subdiaphragmatic two-side vagotomy in nuclei of

vagal nerves and oblongated medulla. Jacobson nuclei in the

spinal cord lateral cornua and stomach and intestinal nerve

plexuses. Dynamics of structural changes in nervous system

different regions after vagotomy was shown. In intramural

nerve ganglionic structure repairs on late post operative

terms, while vagal nerve nuclei in the oblongated medulla

retain significant changes, one of which is the sharp decrease

of neuron number a year after vagotomy. Compensation of

Jacobson nuclei similar to nucl. intermediolateralis was taken

into consideration. So vagotomy is a surgical intervention into

nervous system and into endocrine system associated with it.

481. Vaught, J. L.; Contreras, P. C.; Glicksman, M. A.; Neff, N. T.

Potential utility of rhIGF-1 in neuromuscular and/or

degenerative disease. Ciba-Found-Symp. 1996; 196: 18-27;

discussion 27-38; ISSN: 0300-5208.

NETHERLANDS. Neuromuscular/neurodegenerative disorders,

such as the death of spinal cord motor neurons in amyotrophic

lateral sclerosis (ALS) or the degeneration of spinal cord

motor neuron axons in certain peripheral neuropathies, present

a unique opportunity for therapeutic intervention with

neurotrophic proteins. We have found that in mixed rat

embryonic spinal cord cultures or in purified motor neuron

preparations, recombinant human insulin-like growth factor 1

(rhIGF-1) enhances the survival of motor neurons at EC50

concentrations of 2 nM, consistent with an interaction at the

tyrosine kinase-coupled rhIGF-1 receptor. In a model of

programmed cell death in ovo, administration of rhIGF-1

produces a marked survival of motor neurons. In a variety of

models of predominantly motor neuron or nerve injury in

rodents, administration of rhIGF-1 prevents the death of motor

neurons in neonatal facial nerve lesions, attenuates the loss of

cholinergic phenotype in adult hypoglossal nerve axotomy and

hastens recovery from sciatic nerve crush in mice. In a genetic

model of motor neuron compromise, the wobbler mouse, rhIGF-

1 (1 mg/kg s.c. daily) delayed the deterioration of grip

strength and provided for a more normal distribution of fibre

types. In addition, rhIGF-1 (0.3-1.0 mg/kg s.c. daily) prevents

the motor and/or sensory neuropathy in rodents caused by

vincristine, cisplatinum or Taxol. These combined data

indicate that rhIGF-1 has marked effects on the survival of

compromised motor neurons and the maintenance of their

axons and functional connections. They also suggest the

potential utility of rhIGF-1 for the treatment of diseases such

as ALS and certain neuropathies.. EC 2.3.1.6; 0; 67763-96-6.

482. Vaught, J. L.; Contreras, P. C.; Glicksman, M. A.; Neff, N. T.

Potential utility of rhIGF-1 in neuromuscular and/or

degenerative disease. Ciba-Found-Symp. 1996; 196: 18-27;

discussion 27-38; ISSN: 0300-5208.

NETHERLANDS. Neuromuscular/neurodegenerative disorders,

such as the death of spinal cord motor neurons in amyotrophic

lateral sclerosis (ALS) or the degeneration of spinal cord

motor neuron axons in certain peripheral neuropathies, present

a unique opportunity for therapeutic intervention with

neurotrophic proteins. We have found that in mixed rat

embryonic spinal cord cultures or in purified motor neuron

preparations, recombinant human insulin-like growth factor 1

(rhIGF-1) enhances the survival of motor neurons at EC50

concentrations of 2 nM, consistent with an interaction at the

tyrosine kinase-coupled rhIGF-1 receptor. In a model of

programmed cell death in ovo, administration of rhIGF-1

produces a marked survival of motor neurons. In a variety of

models of predominantly motor neuron or nerve injury in

rodents, administration of rhIGF-1 prevents the death of motor

neurons in neonatal facial nerve lesions, attenuates the loss of

cholinergic phenotype in adult hypoglossal nerve axotomy and

hastens recovery from sciatic nerve crush in mice. In a genetic

model of motor neuron compromise, the wobbler mouse, rhIGF-

1 (1 mg/kg s.c. daily) delayed the deterioration of grip

strength and provided for a more normal distribution of fibre

types. In addition, rhIGF-1 (0.3-1.0 mg/kg s.c. daily) prevents

the motor and/or sensory neuropathy in rodents caused by

vincristine, cisplatinum or Taxol. These combined data

indicate that rhIGF-1 has marked effects on the survival of

compromised motor neurons and the maintenance of their

axons and functional connections. They also suggest the

potential utility of rhIGF-1 for the treatment of diseases such

as ALS and certain neuropathies.. EC 2.3.1.6; 0; 67763-96-6.

483. Vela, J. M.; Dalmau, I.; Acarin, L.; Gonzalez, B.; Castellano, B.

Microglial cell reaction in the gray and white matter in spinal

cords from jimpy mice. An enzyme histochemical study at the

light and electron microscope level. Brain-Res. 1995 Oct 2;

694(1-2): 287-98; ISSN: 0006-8993.

NETHERLANDS. Jimpy is a genetic disorder which results in a

severe hypomyelination in the central nervous system

associated with a variety of astroglial and oligodendroglial

abnormalities. In this study, we examined the morphology and

distribution of microglial cells in spinal cord sections from

jimpy and normal mice at 10-12 and 20-22 days postnatal

using a specific microglial marker, the nucleoside

diphosphatase staining. Compared to those of normal

littermates, the spinal cords of jimpy mice showed an intense

microglial cell reaction in white and gray matter, as revealed

by quantitative analysis and light and electron microscope

study. Microglial reactivity was apparent in all spinal cord

areas, although it was more pronounced in white than in gray

matter. The mean microglial densities in the jimpy white

matter were about threefold (10-12 days) and fivefold (20-22

days) higher than in the normal, whereas in the gray matter,

microglial density in jimpy was about 60% higher than in

normal at both ages. Morphologically, microglial cells in the

normal spinal cord showed a ramified appearance, similar in

size and ramification pattern to those reported in other

normal CNS areas. In contrast, microglial cells in the jimpy

spinal cord showed a reactive morphology, characterized by a

shortening and coarsening of their cell processes, swelling of

their cell body and accumulation of lipid inclusions. Reactive

microglial cells were found in close association with axons

and oligodendroglial cells. The possible role of microglial

cells in hypomyelination is discussed.. EC 3.6; EC 3.6.1.6.

484. Vela, J. M.; Dalmau, I.; Acarin, L.; Gonzalez, B.; Castellano, B.

Microglial cell reaction in the gray and white matter in spinal

cords from jimpy mice. An enzyme histochemical study at the

light and electron microscope level. Brain-Res. 1995 Oct 2;

694(1-2): 287-98; ISSN: 0006-8993.

NETHERLANDS. Jimpy is a genetic disorder which results in a

severe hypomyelination in the central nervous system

associated with a variety of astroglial and oligodendroglial

abnormalities. In this study, we examined the morphology and

distribution of microglial cells in spinal cord sections from

jimpy and normal mice at 10-12 and 20-22 days postnatal

using a specific microglial marker, the nucleoside

diphosphatase staining. Compared to those of normal

littermates, the spinal cords of jimpy mice showed an intense

microglial cell reaction in white and gray matter, as revealed

by quantitative analysis and light and electron microscope

study. Microglial reactivity was apparent in all spinal cord

areas, although it was more pronounced in white than in gray

matter. The mean microglial densities in the jimpy white

matter were about threefold (10-12 days) and fivefold (20-22

days) higher than in the normal, whereas in the gray matter,

microglial density in jimpy was about 60% higher than in

normal at both ages. Morphologically, microglial cells in the

normal spinal cord showed a ramified appearance, similar in

size and ramification pattern to those reported in other

normal CNS areas. In contrast, microglial cells in the jimpy

spinal cord showed a reactive morphology, characterized by a

shortening and coarsening of their cell processes, swelling of

their cell body and accumulation of lipid inclusions. Reactive

microglial cells were found in close association with axons

and oligodendroglial cells. The possible role of microglial

cells in hypomyelination is discussed.. EC 3.6; EC 3.6.1.6.

485. Villanueva, L.; Le Bars, D. The activation of bulbo-spinal controls

by peripheral nociceptive inputs: diffuse noxious inhibitory

controls. Biol-Res. 1995; 28(1): 113-25; ISSN: 0716-9760.

CHILE. Some neurones in the dorsal horn of the spinal cord are

strongly inhibited when a nociceptive stimulus is applied to

any part of the body, distinct from their excitatory receptive

fields. This phenomenon was termed "Diffuse Noxious

Inhibitory Controls" (DNIC). DNIC influence only convergent

neurones, and these inhibitions can be triggered only by

conditioning stimuli which are nociceptive. The inhibitions are

extremely potent, affect all the activities of the convergent

neurones and persist after the removal of the conditioning

stimulus. Only activity of A delta- or A delta- and C-

peripheral fibres can trigger DNIC. DNIC are sustained by a

complex loop which involves supraspinal structures since,

unlike segmental inhibitions, they are not observed in animals

in which the cord has previously been transected at the

cervical level. The ascending and descending limbs of this loop

travel respectively through the ventro-lateral and dorso-

lateral funiculi, respectively. We proposed that DNIC result

from the physiological activation of some brain structures

putatively involved in descending inhibition. However, lesions

of the mesencephalon, including the periaqueductal grey (PAG)

and the rostral ventromedial medulla (RVM), including nucleus

raphe magnus, did not modify DNIC. By contrast, lesions of

subnucleus reticularis dorsalis (SRD) in the caudal medulla

strongly reduced DNIC. Both electrophysiological and

anatomical data support the involvement of SRD neurones in

spino-bulbo-spinal loop(s). In man, very similar results have

been obtained by means of combined psychophysical

measurements and recordings of nociceptive reflexes (RIII

reflex). Painful heterotopic conditioning stimuli depress both

the reflex and the associated painful sensation, with stronger

effects being observed with more intense conditioning stimuli.

By contrast, in tetraplegic patients, heterotopic nociceptive

stimulation did not produce any depression of the RIII reflex.

Observations were also made on patients with cerebral lesions

causing contralateral hemi-analgesia, either a unilateral

thalamic lesion or a lesion of the retro-olivary part of the

medulla (Wallenberg's syndrome). In the patients with

Wallenberg's syndrome, no inhibitions were observed when the

nociceptive conditioning stimuli were applied to the affected

side whereas if these stimuli were applied to the normal side

they triggered inhibitory effects and post-effects very similar

to those seen in normal subjects. These results show that in

humans, brainstem--probably reticular--structures seem to

play a key role in these phenomena. The data suggest that

nociceptive stimuli, even though there are unquestionably

perceived as being painful activate certain inhibitory controls

which originate in the brainstem. Since all convergent

neurones are subject to DNIC, one can make the assertion that

the transmission of nociceptive signals towards higher

centres is under the influence of these controls. In other

words, the descending inhibitory controls may play a

physiological role in the detection of nociceptive signals. It is

proposed that DNIC constitute both a filter which allows the

extraction of the signal for pain and an amplifier in the

transmission system which increases the potential alarm

function of the nociceptive signals. This hypothesis is

supported by the finding that DNIC are blocked by low doses of

morphine in both rat and man.

486. Villanueva, L.; Le Bars, D. The activation of bulbo-spinal controls

by peripheral nociceptive inputs: diffuse noxious inhibitory

controls. Biol-Res. 1995; 28(1): 113-25; ISSN: 0716-9760.

CHILE. Some neurones in the dorsal horn of the spinal cord are

strongly inhibited when a nociceptive stimulus is applied to

any part of the body, distinct from their excitatory receptive

fields. This phenomenon was termed "Diffuse Noxious

Inhibitory Controls" (DNIC). DNIC influence only convergent

neurones, and these inhibitions can be triggered only by

conditioning stimuli which are nociceptive. The inhibitions are

extremely potent, affect all the activities of the convergent

neurones and persist after the removal of the conditioning

stimulus. Only activity of A delta- or A delta- and C-

peripheral fibres can trigger DNIC. DNIC are sustained by a

complex loop which involves supraspinal structures since,

unlike segmental inhibitions, they are not observed in animals

in which the cord has previously been transected at the

cervical level. The ascending and descending limbs of this loop

travel respectively through the ventro-lateral and dorso-

lateral funiculi, respectively. We proposed that DNIC result

from the physiological activation of some brain structures

putatively involved in descending inhibition. However, lesions

of the mesencephalon, including the periaqueductal grey (PAG)

and the rostral ventromedial medulla (RVM), including nucleus

raphe magnus, did not modify DNIC. By contrast, lesions of

subnucleus reticularis dorsalis (SRD) in the caudal medulla

strongly reduced DNIC. Both electrophysiological and

anatomical data support the involvement of SRD neurones in

spino-bulbo-spinal loop(s). In man, very similar results have

been obtained by means of combined psychophysical

measurements and recordings of nociceptive reflexes (RIII

reflex). Painful heterotopic conditioning stimuli depress both

the reflex and the associated painful sensation, with stronger

effects being observed with more intense conditioning stimuli.

By contrast, in tetraplegic patients, heterotopic nociceptive

stimulation did not produce any depression of the RIII reflex.

Observations were also made on patients with cerebral lesions

causing contralateral hemi-analgesia, either a unilateral

thalamic lesion or a lesion of the retro-olivary part of the

medulla (Wallenberg's syndrome). In the patients with

Wallenberg's syndrome, no inhibitions were observed when the

nociceptive conditioning stimuli were applied to the affected

side whereas if these stimuli were applied to the normal side

they triggered inhibitory effects and post-effects very similar

to those seen in normal subjects. These results show that in

humans, brainstem--probably reticular--structures seem to

play a key role in these phenomena. The data suggest that

nociceptive stimuli, even though there are unquestionably

perceived as being painful activate certain inhibitory controls

which originate in the brainstem. Since all convergent

neurones are subject to DNIC, one can make the assertion that

the transmission of nociceptive signals towards higher

centres is under the influence of these controls. In other

words, the descending inhibitory controls may play a

physiological role in the detection of nociceptive signals. It is

proposed that DNIC constitute both a filter which allows the

extraction of the signal for pain and an amplifier in the

transmission system which increases the potential alarm

function of the nociceptive signals. This hypothesis is

supported by the finding that DNIC are blocked by low doses of

morphine in both rat and man.

487. Vinay, L.; Clarac, F. CGP 35348 and CGP 55845A block the

baclofen-induced depression of dorsal root evoked potentials

in lumbar motoneurons of the neonatal rat. Neurosci-Lett.

1996 Aug 23; 214(2-3): 103-6; ISSN: 0304-3940.

IRELAND. In vitro brainstem-spinal cord preparations isolated

from neonatal (0-5 days old) rats were used to investigate the

GABAB receptor-mediated modulation of the dorsal root

evoked potentials in lumbar motoneurons recorded

intracellularly. The GABAB receptor agonist, baclofen, at low

concentrations (1-10 microM), caused a reduction of the

amplitude of the monosynaptic excitatory postsynaptic

potential (EPSP), in a concentration-dependent manner. The

depression of EPSPs was likely exerted at a presynaptic level

since it occurred without any significant change of the passive

membrane properties of the motoneurons. The two GABAB

receptor antagonists, CGP 35348 and CGP 55845A blocked the

effects of baclofen. These two compounds may be useful tools

to study the evolution of GABAB receptor-mediated

presynaptic inhibition during ontogenesis.. 0; 0; 0; 0; 0; 0;

1134-47-0; 123690-79-9; 148056-42-2.

488. Vinay, L.; Clarac, F. CGP 35348 and CGP 55845A block the

baclofen-induced depression of dorsal root evoked potentials

in lumbar motoneurons of the neonatal rat. Neurosci-Lett.

1996 Aug 23; 214(2-3): 103-6; ISSN: 0304-3940.

IRELAND. In vitro brainstem-spinal cord preparations isolated

from neonatal (0-5 days old) rats were used to investigate the

GABAB receptor-mediated modulation of the dorsal root

evoked potentials in lumbar motoneurons recorded

intracellularly. The GABAB receptor agonist, baclofen, at low

concentrations (1-10 microM), caused a reduction of the

amplitude of the monosynaptic excitatory postsynaptic

potential (EPSP), in a concentration-dependent manner. The

depression of EPSPs was likely exerted at a presynaptic level

since it occurred without any significant change of the passive

membrane properties of the motoneurons. The two GABAB

receptor antagonists, CGP 35348 and CGP 55845A blocked the

effects of baclofen. These two compounds may be useful tools

to study the evolution of GABAB receptor-mediated

presynaptic inhibition during ontogenesis.. 0; 0; 0; 0; 0; 0;

1134-47-0; 123690-79-9; 148056-42-2.

489. von, der Emde G.; Bell, C. C. Nucleus preeminentialis of mormyrid

fish, a center for recurrent electrosensory feedback. I.

Electrosensory and corollary discharge responses. J-

Neurophysiol. 1996 Sep; 76(3): 1581-96; ISSN: 0022-3077.

UNITED-STATES. 1. The nucleus preeminentialis (PE) is a large

central structure that projects both directly and indirectly to

the electrosensory lobe (ELL) where the primary afferents

from electroreceptors terminate. PE receives electrosensory

input directly from ELL and also from higher stages of the

electrosensory pathway. PE is thus an important part of a

central feedback loop that returns electrosensory information

from higher stages of the system to the initial stage in ELL. 2.

This study describes the field potentials and single-unit

activity that are evoked in PE by electrosensory stimuli and by

corollary discharge signals associated with the motor

command that drives the electric organ to discharge. All

recordings were extracellular in this study. 3. Two types of

negative-going corollary discharge-evoked field potentials

were found in PE: 1) a shallow, long-lasting negative wave

with a latency at the peak of approximately 11 ms, and 2) a

more sharply falling and larger negative wave with a shorter

latency at the peak of approximately 9 ms. The long-latency

wave was predominant in the dorsolateral and posterior parts

of PE, whereas the short-latency wave was predominant in the

medial and rostral regions. Both waves were only found in PE

and thus can serve for its identification. 4. Electrosensory

stimuli given either locally to a restricted skin region or

symmetrically to the entire body evoked characteristic field

potentials in both regions of PE. The mean latency between the

stimulus and the peak of the response was 6.9 ms in the early

negativity region and 12.2 ms in the late negative region. The

responses to such stimuli were strongly facilitated by the

electric organ corollary discharge. 5. Field potential responses

to the electric organ corollary discharge were markedly

plastic. Responses to the corollary discharge plus a paired

electrosensory stimulus decreased over time and the response

to the corollary discharge alone was markedly enhanced after

a period of such pairing. 6. Local electrosensory stimulation of

the skin showed that the caudal-rostral body axis is mapped

from dorsal-medial to ventral-lateral in PE. The same

somatotopy was found in the regions of the early and late

negatives. The ventral and dorsal body appeared not to be

separately mapped in PE. The areas representing the head and

chin appendage ("Schnauzenorgan") are especially large in PE,

due presumably to the high density of electroreceptors in

these areas. 7. Two main types of units were recorded in PE: 1)

inhibitory (I) cells with a corollary discharge response that

was inhibited by an electrosensory stimulus to the center of

their receptive fields; and 2) excitatory (E) cells with an

excitatory response to electrosensory stimuli that was

facilitated by the corollary discharge. Some of the E cells

responded to the corollary discharge alone and some did not.

Most cells appeared to be responding to input from

mormyromast electroreceptors, but a few cells were driven by

ampullary electroreceptors and a few by Knollenorgan

electroreceptors. 8. The corollary discharge effects on I cells

and E cells were plastic and depended on previous pairing with

a sensory stimulus. The corollary discharge facilitation of E

cells and inhibition of I cells decreased during pairing with a

sensory stimulus, and the corollary discharge-driven

excitation of I cells was much larger after pairing than before.

9. The results provide an initial overview of a major

component in the control of electrosensory information

processing by recurrent feedback from higher stages of the

system.

490. von, der Emde G.; Bell, C. C. Nucleus preeminentialis of mormyrid

fish, a center for recurrent electrosensory feedback. I.

Electrosensory and corollary discharge responses. J-

Neurophysiol. 1996 Sep; 76(3): 1581-96; ISSN: 0022-3077.

UNITED-STATES. 1. The nucleus preeminentialis (PE) is a large

central structure that projects both directly and indirectly to

the electrosensory lobe (ELL) where the primary afferents

from electroreceptors terminate. PE receives electrosensory

input directly from ELL and also from higher stages of the

electrosensory pathway. PE is thus an important part of a

central feedback loop that returns electrosensory information

from higher stages of the system to the initial stage in ELL. 2.

This study describes the field potentials and single-unit

activity that are evoked in PE by electrosensory stimuli and by

corollary discharge signals associated with the motor

command that drives the electric organ to discharge. All

recordings were extracellular in this study. 3. Two types of

negative-going corollary discharge-evoked field potentials

were found in PE: 1) a shallow, long-lasting negative wave

with a latency at the peak of approximately 11 ms, and 2) a

more sharply falling and larger negative wave with a shorter

latency at the peak of approximately 9 ms. The long-latency

wave was predominant in the dorsolateral and posterior parts

of PE, whereas the short-latency wave was predominant in the

medial and rostral regions. Both waves were only found in PE

and thus can serve for its identification. 4. Electrosensory

stimuli given either locally to a restricted skin region or

symmetrically to the entire body evoked characteristic field

potentials in both regions of PE. The mean latency between the

stimulus and the peak of the response was 6.9 ms in the early

negativity region and 12.2 ms in the late negative region. The

responses to such stimuli were strongly facilitated by the

electric organ corollary discharge. 5. Field potential responses

to the electric organ corollary discharge were markedly

plastic. Responses to the corollary discharge plus a paired

electrosensory stimulus decreased over time and the response

to the corollary discharge alone was markedly enhanced after

a period of such pairing. 6. Local electrosensory stimulation of

the skin showed that the caudal-rostral body axis is mapped

from dorsal-medial to ventral-lateral in PE. The same

somatotopy was found in the regions of the early and late

negatives. The ventral and dorsal body appeared not to be

separately mapped in PE. The areas representing the head and

chin appendage ("Schnauzenorgan") are especially large in PE,

due presumably to the high density of electroreceptors in

these areas. 7. Two main types of units were recorded in PE: 1)

inhibitory (I) cells with a corollary discharge response that

was inhibited by an electrosensory stimulus to the center of

their receptive fields; and 2) excitatory (E) cells with an

excitatory response to electrosensory stimuli that was

facilitated by the corollary discharge. Some of the E cells

responded to the corollary discharge alone and some did not.

Most cells appeared to be responding to input from

mormyromast electroreceptors, but a few cells were driven by

ampullary electroreceptors and a few by Knollenorgan

electroreceptors. 8. The corollary discharge effects on I cells

and E cells were plastic and depended on previous pairing with

a sensory stimulus. The corollary discharge facilitation of E

cells and inhibition of I cells decreased during pairing with a

sensory stimulus, and the corollary discharge-driven

excitation of I cells was much larger after pairing than before.

9. The results provide an initial overview of a major

component in the control of electrosensory information

processing by recurrent feedback from higher stages of the

system.

491. Vos, J. P.; Giudici, M. L.; van, der Bijl P.; Lopes Cardozo, M.

Synthesis of sphingomyelin by oligodendrocytes--how and

where? J-Lipid-Mediat-Cell-Signal. 1996 Sep; 14(1-3): 313-9;

ISSN: 0929-7855.

NETHERLANDS. Sphingomyelin (SM) biosynthesis in cultured

oligodendrocytes (OC) was evaluated: (i) with [14C] tracers

(choline, ethanolamine, serine) to pinpoint the major

metabolic routes; (ii) with fluorescent and truncated,

radiolabeled ceramide analogs to determine the relative

activities of SM-synthase in intra-and extra-Golgi

compartments of OC. In contrast to a general contention in the

literature that SM synthase is absent from the brain, our data

show that (choline-->CDP-choline-->phosphatidylcholine (PC)-

->SM) is the major anabolic route with only a minor

contribution to PC via methylation of

phosphatidylethanolamine (PE). SM synthase activity was found

to be equally divided between intra- and extra-Golgi

compartments of OC. Moreover, significant SM-synthase

activity was recovered in purified myelin preparations. Our

results shed new light on the possible involvement of

sphingolipid-derived mediators in myelination.. 0.

492. Vos, J. P.; Giudici, M. L.; van, der Bijl P.; Lopes Cardozo, M.

Synthesis of sphingomyelin by oligodendrocytes--how and

where? J-Lipid-Mediat-Cell-Signal. 1996 Sep; 14(1-3): 313-9;

ISSN: 0929-7855.

NETHERLANDS. Sphingomyelin (SM) biosynthesis in cultured

oligodendrocytes (OC) was evaluated: (i) with [14C] tracers

(choline, ethanolamine, serine) to pinpoint the major

metabolic routes; (ii) with fluorescent and truncated,

radiolabeled ceramide analogs to determine the relative

activities of SM-synthase in intra-and extra-Golgi

compartments of OC. In contrast to a general contention in the

literature that SM synthase is absent from the brain, our data

show that (choline-->CDP-choline-->phosphatidylcholine (PC)-

->SM) is the major anabolic route with only a minor

contribution to PC via methylation of

phosphatidylethanolamine (PE). SM synthase activity was found

to be equally divided between intra- and extra-Golgi

compartments of OC. Moreover, significant SM-synthase

activity was recovered in purified myelin preparations. Our

results shed new light on the possible involvement of

sphingolipid-derived mediators in myelination.. 0.

493. Wada, N.; Akenaga, K.; Takayama, R.; Tokuriki, M. Descending

pathways from the medial longitudinal fasciculus and lateral

vestibular nucleus to tail motoneurons in the decerebrate cat.

Arch-Ital-Biol. 1996 Jul; 134(3): 207-15; ISSN: 0003-9829.

ITALY. Responses of motoneurons supplying two tail muscles

(m. extensor caudae lateralis [ECL] and m. flexor caudae longus

[FCL]) to stimulation of the medial longitudinal fasciculus

(MLF) and lateral vestibular nucleus (LVN) were studied using

intracellular recording in the decerebrate cat. Stimulation of

the MLF and the LVN produced mainly excitatory postsynaptic

potentials (EPSPs) or mixed PSPs (EPSP/IPSPs), but inhibitory

postsynaptic potentials (IPSPs) were also observed in a few

motoneurons. The segmental latencies of early PSPs produced

by MLF or LVN stimulation were distributed over a wide range,

and PSPs with a segmental latency of mono- or disynaptic

origin were observed in ECL and FCL motoneurons. The spatial

facilitation technique indicated convergence of the descending

pathways from MLF and LVN on a common interneuron.

494. Wada, N.; Akenaga, K.; Takayama, R.; Tokuriki, M. Descending

pathways from the medial longitudinal fasciculus and lateral

vestibular nucleus to tail motoneurons in the decerebrate cat.

Arch-Ital-Biol. 1996 Jul; 134(3): 207-15; ISSN: 0003-9829.

ITALY. Responses of motoneurons supplying two tail muscles

(m. extensor caudae lateralis [ECL] and m. flexor caudae longus

[FCL]) to stimulation of the medial longitudinal fasciculus

(MLF) and lateral vestibular nucleus (LVN) were studied using

intracellular recording in the decerebrate cat. Stimulation of

the MLF and the LVN produced mainly excitatory postsynaptic

potentials (EPSPs) or mixed PSPs (EPSP/IPSPs), but inhibitory

postsynaptic potentials (IPSPs) were also observed in a few

motoneurons. The segmental latencies of early PSPs produced

by MLF or LVN stimulation were distributed over a wide range,

and PSPs with a segmental latency of mono- or disynaptic

origin were observed in ECL and FCL motoneurons. The spatial

facilitation technique indicated convergence of the descending

pathways from MLF and LVN on a common interneuron.

495. Wan, Q.; Liao, M.; Brown, G. M.; Pang, S. F. Localization and

characterization of melatonin receptors in the rabbit spinal

cord. Neurosci-Lett. 1996 Feb 2; 204(1-2): 77-80; ISSN: 0304-

3940.

IRELAND. Melatonin receptors in the rabbit spinal cord were

studied. Using in vitro quantitative autoradiography we have

localized and characterized 2-[125I]iodomelatonin ([125I]MEL)

binding sites in the central gray substance (lamina X) of the

rabbit spinal cord. Saturation study revealed a single class of

high affinity binding sites in the central gray substance with

an equilibrium dissociation constant (Kd) of 38.8 +/- 5.25 pM

and a maximum number of binding sites of 5.69 +/- 0.84

fmol/mg protein in the mid-light period. These [125I]MEL

binding sites were highly specific for melatonin. Coincubation

with 10 microM or 50 microM guanosine 5'-O-(3-

thiotriphosphate) produced a significant change in Kd. These

results suggest that melatonin receptors in the rabbit spinal

cord are coupled to a guanine-nucleotide-binding protein (G-

protein). Our studies suggest that melatonin exerts a direct

action on the rabbit spinal cord.. 0; 0; 0; 0; 0; 37589-80-3;

73-31-4; 93515-00-5.

496. Wan, Q.; Liao, M.; Brown, G. M.; Pang, S. F. Localization and

characterization of melatonin receptors in the rabbit spinal

cord. Neurosci-Lett. 1996 Feb 2; 204(1-2): 77-80; ISSN: 0304-

3940.

IRELAND. Melatonin receptors in the rabbit spinal cord were

studied. Using in vitro quantitative autoradiography we have

localized and characterized 2-[125I]iodomelatonin ([125I]MEL)

binding sites in the central gray substance (lamina X) of the

rabbit spinal cord. Saturation study revealed a single class of

high affinity binding sites in the central gray substance with

an equilibrium dissociation constant (Kd) of 38.8 +/- 5.25 pM

and a maximum number of binding sites of 5.69 +/- 0.84

fmol/mg protein in the mid-light period. These [125I]MEL

binding sites were highly specific for melatonin. Coincubation

with 10 microM or 50 microM guanosine 5'-O-(3-

thiotriphosphate) produced a significant change in Kd. These

results suggest that melatonin receptors in the rabbit spinal

cord are coupled to a guanine-nucleotide-binding protein (G-

protein). Our studies suggest that melatonin exerts a direct

action on the rabbit spinal cord.. 0; 0; 0; 0; 0; 37589-80-3;

73-31-4; 93515-00-5.

497. Wang, L. H.; Strittmatter, S. M. A family of rat CRMP genes is

differentially expressed in the nervous system. J-Neurosci.

1996 Oct 1; 16(19): 6197-207; ISSN: 0270-6474.

UNITED-STATES. Members of the collapsin/semaphorin family

play an important role in creating the complex pattern of

neuronal connectivity. Inhibition of growth cone motility by

chick collapsin is mediated by the intraneuronal protein CRMP-

62. We have now isolated four rat sequences that are highly

related to chick CRMP-62. All four genes are expressed

exclusively in the nervous system and primarily during

development. Rat CRMP-2/TOAD-64 is most closely related to

chick CRMP-62 and is the most widely expressed CRMP within

the nervous system. Rat CRMP-1 and CRMP-4/rUlip are

expressed during discrete periods of neuronal development and

are not found in the adult nervous system. Rat CRMP-3 has a

distinct distribution, being expressed transiently in

developing spinal cord and selectively in the postnatal

cerebellum. The differential expression of these genes

suggests that CRMPs may transduce signals from different

semaphorins and that semaphorins may regulate the plasticity

of the adult nervous system.. 0; 0.

498. Wang, L. H.; Strittmatter, S. M. A family of rat CRMP genes is

differentially expressed in the nervous system. J-Neurosci.

1996 Oct 1; 16(19): 6197-207; ISSN: 0270-6474.

UNITED-STATES. Members of the collapsin/semaphorin family

play an important role in creating the complex pattern of

neuronal connectivity. Inhibition of growth cone motility by

chick collapsin is mediated by the intraneuronal protein CRMP-

62. We have now isolated four rat sequences that are highly

related to chick CRMP-62. All four genes are expressed

exclusively in the nervous system and primarily during

development. Rat CRMP-2/TOAD-64 is most closely related to

chick CRMP-62 and is the most widely expressed CRMP within

the nervous system. Rat CRMP-1 and CRMP-4/rUlip are

expressed during discrete periods of neuronal development and

are not found in the adult nervous system. Rat CRMP-3 has a

distinct distribution, being expressed transiently in

developing spinal cord and selectively in the postnatal

cerebellum. The differential expression of these genes

suggests that CRMPs may transduce signals from different

semaphorins and that semaphorins may regulate the plasticity

of the adult nervous system.. 0; 0.

499. Wang, X. M.; Terman, J. R.; Martin, G. F. Evidence for growth of

supraspinal axons through the lesion after transection of the

thoracic spinal cord in the developing opossum Didelphis

virginiana. J-Comp-Neurol. 1996 Jul 15; 371(1): 104-15; ISSN:

0021-9967.

UNITED-STATES. In the present study, we asked whether

supraspinal axons grow through a complete transection of the

spinal cord in the developing opossum Didelphis virginiana.

When the thoracic cord was transected at postnatal day (PD) 5

and bilateral injections of Fast Blue (FB) were made four

segments caudal to the lesion 30-40 days later, FB-containing

neurons were found in each of the supraspinal nuclei labeled by

comparable injections in age-matched unlesioned controls.

Continuity between the cut ends of the cord was obviously

gross when the animals were killed, and histologically

recognizable spinal cord was present at the lesion site. When

the same procedure was followed on pups subjected to

transection at PD12, FB-containing neurons were still present

at supraspinal levels, but they appeared to be fewer in number

than in the PD5 cases or the age-matched controls, and none

were found within the medial pontine reticular and lateral

vestibular nuclei. When the lesion was made at PD20, labeled

neurons were even fewer in number, and when it was made at

PD26, they were restricted to the medullary raphe and the red

nuclei. There was no evidence for growth of supraspinal axons

across lesions made at PD33. We conclude that supraspinal

axons grow through the lesion after transection of the spinal

cord in neonatal opossums and that the critical period for

growth of reticulospinal and vestibulospinal axons through the

lesion ends earlier than that for comparable growth of

raphespinal and rubrospinal axons.

500. Wang, X. M.; Terman, J. R.; Martin, G. F. Evidence for growth of

supraspinal axons through the lesion after transection of the

thoracic spinal cord in the developing opossum Didelphis

virginiana. J-Comp-Neurol. 1996 Jul 15; 371(1): 104-15; ISSN:

0021-9967.

UNITED-STATES. In the present study, we asked whether

supraspinal axons grow through a complete transection of the

spinal cord in the developing opossum Didelphis virginiana.

When the thoracic cord was transected at postnatal day (PD) 5

and bilateral injections of Fast Blue (FB) were made four

segments caudal to the lesion 30-40 days later, FB-containing

neurons were found in each of the supraspinal nuclei labeled by

comparable injections in age-matched unlesioned controls.

Continuity between the cut ends of the cord was obviously

gross when the animals were killed, and histologically

recognizable spinal cord was present at the lesion site. When

the same procedure was followed on pups subjected to

transection at PD12, FB-containing neurons were still present

at supraspinal levels, but they appeared to be fewer in number

than in the PD5 cases or the age-matched controls, and none

were found within the medial pontine reticular and lateral

vestibular nuclei. When the lesion was made at PD20, labeled

neurons were even fewer in number, and when it was made at

PD26, they were restricted to the medullary raphe and the red

nuclei. There was no evidence for growth of supraspinal axons

across lesions made at PD33. We conclude that supraspinal

axons grow through the lesion after transection of the spinal

cord in neonatal opossums and that the critical period for

growth of reticulospinal and vestibulospinal axons through the

lesion ends earlier than that for comparable growth of

raphespinal and rubrospinal axons.

501. Warren, L.; Wrigley, J. M.; Yoels, W. C.; Fine, P. R. Factors

associated with life satisfaction among a sample of persons

with neurotrauma. J-Rehabil-Res-Dev. 1996 Oct; 33(4): 404-8;

ISSN: 0748-7711.

UNITED-STATES. Factors were examined that are associated

with life satisfaction one year post-discharge for persons

with a spinal cord (SCI) or traumatic brain injury (TBI).

Findings show persons with SCI or TBI should be considered as

two distinct groups with regard to factors affecting life

satisfaction. Different strategies might be considered to

affect either group. Three psychosocial variables significantly

increased life satisfaction for persons with SCI: closeness to

family, the level of family activities, and blaming oneself for

the injury. For persons with TBI, total family satisfaction,

blaming oneself for the injury, being employed, being married,

and having memory and bowel independence significantly

increased life satisfaction. For persons with TBI, there was a

difference in the number of factors affecting life satisfaction

dependent on whether the persons blamed themselves or not.

Those who do not blame themselves show a greater number of

functional activities as indicators for their self-satisfaction.

502. Warren, L.; Wrigley, J. M.; Yoels, W. C.; Fine, P. R. Factors

associated with life satisfaction among a sample of persons

with neurotrauma. J-Rehabil-Res-Dev. 1996 Oct; 33(4): 404-8;

ISSN: 0748-7711.

UNITED-STATES. Factors were examined that are associated

with life satisfaction one year post-discharge for persons

with a spinal cord (SCI) or traumatic brain injury (TBI).

Findings show persons with SCI or TBI should be considered as

two distinct groups with regard to factors affecting life

satisfaction. Different strategies might be considered to

affect either group. Three psychosocial variables significantly

increased life satisfaction for persons with SCI: closeness to

family, the level of family activities, and blaming oneself for

the injury. For persons with TBI, total family satisfaction,

blaming oneself for the injury, being employed, being married,

and having memory and bowel independence significantly

increased life satisfaction. For persons with TBI, there was a

difference in the number of factors affecting life satisfaction

dependent on whether the persons blamed themselves or not.

Those who do not blame themselves show a greater number of

functional activities as indicators for their self-satisfaction.

503. Wei, X.; Sulik, K. K. Pathogenesis of caudal

dysgenesis/sirenomelia induced by ochratoxin A in chick

embryos. Teratology. 1996 Jun; 53(6): 378-91; ISSN: 0040-

3709.

UNITED-STATES. Caudal dysgenesis/sirenomelia is a

malformation complex for which the pathogenesis is

controversial. This report describes the particular

vulnerability of specific caudal structures to Ochratoxin A

(OA), a fungal toxin, as the basis for caudal dysgenesis in an

avian model. The experimental procedure involved injection of

1 microgram of OA into the air sac of eggs that had been

incubated for 48 hours prior to treatment (i.e., embryos that

had reached Hamburger and Hamilton stage 9-10 (6-10 somite

pairs) [Hamburger and Hamilton (1951) Dev. Dyn. 195:231-272]

by the time of treatment). Six to twelve hours following OA

injection, excessive cell death, as shown by vital staining and

routine histology, was evident in selected cell populations,

including cells of the caudal-most mesoderm (the mesoderm

that apparently forms the external genitalia and median

infraumbilical region), the tail bud, and the neural tube caudal

to the wing buds (corresponding to the level of the presomitic

mesoderm). The notochord was not severely affected, although

there were degenerative changes in the presomitic mesoderm.

Except for positional abnormalities, development of the

lateral plate mesoderm from which the leg buds are derived

appeared relatively normal in most of the treated embryos. Six

days post-treatment, varying degrees of caudal dysgenesis,

presenting in severely affected specimens as sirenomelia,

were observed in approximately 30% of the surviving treated

embryos. The potential basis for the differential vulnerability

of the affected cell populations and, therefore, the cellular

basis for the genesis of caudal dysgenesis/sirenomelia in this

model are discussed.. 0; 0; 303-47-9.

504. Wei, X.; Sulik, K. K. Pathogenesis of caudal

dysgenesis/sirenomelia induced by ochratoxin A in chick

embryos. Teratology. 1996 Jun; 53(6): 378-91; ISSN: 0040-

3709.

UNITED-STATES. Caudal dysgenesis/sirenomelia is a

malformation complex for which the pathogenesis is

controversial. This report describes the particular

vulnerability of specific caudal structures to Ochratoxin A

(OA), a fungal toxin, as the basis for caudal dysgenesis in an

avian model. The experimental procedure involved injection of

1 microgram of OA into the air sac of eggs that had been

incubated for 48 hours prior to treatment (i.e., embryos that

had reached Hamburger and Hamilton stage 9-10 (6-10 somite

pairs) [Hamburger and Hamilton (1951) Dev. Dyn. 195:231-272]

by the time of treatment). Six to twelve hours following OA

injection, excessive cell death, as shown by vital staining and

routine histology, was evident in selected cell populations,

including cells of the caudal-most mesoderm (the mesoderm

that apparently forms the external genitalia and median

infraumbilical region), the tail bud, and the neural tube caudal

to the wing buds (corresponding to the level of the presomitic

mesoderm). The notochord was not severely affected, although

there were degenerative changes in the presomitic mesoderm.

Except for positional abnormalities, development of the

lateral plate mesoderm from which the leg buds are derived

appeared relatively normal in most of the treated embryos. Six

days post-treatment, varying degrees of caudal dysgenesis,

presenting in severely affected specimens as sirenomelia,

were observed in approximately 30% of the surviving treated

embryos. The potential basis for the differential vulnerability

of the affected cell populations and, therefore, the cellular

basis for the genesis of caudal dysgenesis/sirenomelia in this

model are discussed.. 0; 0; 303-47-9.

505. Wiesenfeld Hallin, Z.; Xu, X. J. The role of cholecystokinin in

nociception, neuropathic pain and opiate tolerance. Regul-Pept.

1996 Aug 27; 65(1): 23-8; ISSN: 0167-0115.

NETHERLANDS. 0; 0; 9011-97-6.

506. Wiesenfeld Hallin, Z.; Xu, X. J. The role of cholecystokinin in

nociception, neuropathic pain and opiate tolerance. Regul-Pept.

1996 Aug 27; 65(1): 23-8; ISSN: 0167-0115.

NETHERLANDS. 0; 0; 9011-97-6.

507. Williams, T. L.; Ince, P. G.; Oakley, A. E.; Shaw, P. J. An

immunocytochemical study of the distribution of AMPA

selective glutamate receptor subunits in the normal human

motor system. Neuroscience. 1996 Sep; 74(1): 185-98; ISSN:

0306-4522.

UNITED-STATES. Glutamate is the major mediator of fast

excitatory neurotransmission in the mammalian central

nervous system. Disturbances of this neurotransmitter system

have been implicated in chronic degenerative neurological

disease. Recently, major advances in our knowledge and

understanding of the molecular biology of the glutamatergic

receptor system have been made. It is now known that

functional glutamate receptors consist of various

combinations of some 20 identified subunits. A growing body

of circumstantial evidence suggests that the non-N-methyl-D-

aspartate subtype of glutamate receptors may mediate, at

least in part, the selective motor neuron death seen in the

human neurodegenerative disease amyotrophic lateral

sclerosis. We have used subunit specific immunocytochemistry

to study the distribution and potential subunit composition of

the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic

acid (AMPA) selective glutamate receptors, (a subgroup of

non-N-methyl-D-aspartate selective glutamate receptors

formed by combinations of GluR1-4 subunits), in the human

motor system. Motor neurons in the spinal cord, brainstem, and

motor cortex were relatively strongly immunoreactive with

the GluR2/3 subunit antibody, moderately so with the GluR4

subunit antibody, and showed relatively low levels of

immunoreactivity with the GluR1 sub