Required readings for Cranial Nerve module by Prof. Carrick

Anatomy of the Cranial Nerves by Laine & Smoker

Understanding the Brain Stem, by Daniels, et al

Both from Neuroimaging Clinics of North America, Vol 8, No 1, February 1998

 

These are the references utilized by Prof Carrick in preparing his lecture on Cranial nerves.

Bibliography

 

1. Abele, M.; Burk, K.; Andres, F.; Topka, H.; Laccone, F.; Bosch, S.;

Brice, A.; Cancel, G.; Dichgans, J.; Klockgether, T. Autosomal

dominant cerebellar ataxia type I. Nerve conduction and evoked

potential studies in families with SCA1, SCA2 and SCA3.

Brain. 1997 Dec; 120( Pt 12): 2141-8; ISSN: 0006-8950.

ENGLAND. Forty-one patients suffering from autosomal

dominant cerebellar ataxia type I (ADCA-I) were subjected to

a genotype-phenotype correlation analysis using molecular

genetic assignment to the spinocerebellar ataxia type 1, 2 or 3

(SCA1, -2 or -3) genetic locus, clinical examination and nerve

conduction as well as evoked potential studies. Pyramidal

tract signs, pale discs, and dysphagia were more frequent in

SCA1 compared with SCA2 and SCA3 patients, while double

vision occurred less frequently. Visual evoked potentials and

motor evoked potentials following transcranial magnetic

stimulation were abnormal in almost all SCA1 patients, but

only in a minority of SCA2 and SCA3 patients. In contrast,

somatosensory evoked potentials were delayed or absent in the

majority of patients with no significant differences between

the mutations. Abnormalities of brainstem auditory evoked

potentials were found in about half of the patients

irrespective of the underlying mutation. In addition, reduced

sensory nerve action potentials, suggesting sensory axonal

neuropathy were found in all three mutations. These findings

provide electrophysiological evidence that pyramidal and

visual pathways are differentially affected in SCA1, SCA2 and

SCA3 patients.

2. Acri, J. B.; Wong, G.; Lyon, T.; Witkin, J. M.; Basile, A. S.

Localization and pharmacological characterization of pigeon

diazepam-insensitive GABAA receptors. Neuroscience. 1997

Mar; 77(2): 371-8; ISSN: 0306-4522.

UNITED-STATES. Transduction mechanisms associated with

ligand binding at diazepam-insensitive subtypes of GABAA

receptors remain largely unknown, but unique behavioral

effects of ligands binding at these sites have been reported in

pigeons. The present study further evaluated the

pharmacological characteristics of diazepam-insensitive

GABAA receptors in pigeon brain, using [3H]Ro 15-4513.

Autoradiography detected diazepam-insensitive

benzodiazepine sites on GABAA receptors in a number of brain

regions, with the highest densities present in the olfactory

bulb, hippocampus, thalamic nuclei and cerebellar granule cell

layers, with densities of approximately 10-20% of total

benzodiazepine receptor binding. Saturation analysis revealed

significant densities (approximately 10% of total

benzodiazepine receptor binding) of extracerebellar diazepam-

insensitive benzodiazepine receptors in optic lobe,

hippocampus, and brainstem compared to 27% in cerebellum.

As reported for mammalian diazepam-sensitive

benzodiazepine receptors, GABA (50 microM) generally

increased the affinities of agonists and partial agonists, had

little effect on the affinities of antagonists, and decreased

the affinity of an inverse agonist for pigeon cerebellar

diazepam-sensitive benzodiazepine receptors. GABA

modulation of ligand binding to diazepam-insensitive

benzodiazepine receptors was less than that observed for

diazepam-sensitive sites, and no positive modulation was

observed. These results demonstrate the presence of

cerebellar and extracerebellar diazepam-insensitive

benzodiazepine receptors in pigeon brain, with distribution

patterns and pharmacology similar to those reported in

mammals. The comparable central localization and

pharmacological properties of drugs at diazepam-sensitive and

-insensitive benzodiazepine receptors in pigeons and rats

attests to the evolutionary conservation of GABAA systems..

0; 0; 0; 0; 0; 0; 439-14-5; 56-12-2; 91917-65-6.

3. Adle Biassette, H.; Chetritt, J.; Bergemer Fouquet, A. M.; Wechsler,

J.; Mussini, J. M.; Gray, F. Pathology of the central nervous

system in Chester-Erdheim disease: report of three cases. J-

Neuropathol-Exp-Neurol. 1997 Nov; 56(11): 1207-16; ISSN:

0022-3069.

UNITED-STATES. Chester-Erdheim disease is a rare form of

non-Langerhans cell histiocytosis consisting of disseminated

xanthogranulomatous infiltration and fibrosis that primarily

involves the bones, visceral organs and systemic fatty spaces.

Involvement of the central nervous system is variable, and

neuropathological features have seldom been documented. We

report the neuropathological findings in 3 autopsy cases. One

patient had radiological and pathological bone changes

characteristic of Chester-Erdheim disease. Neuropathology

revealed multiple characteristic xanthogranulomas

disseminated in the cerebral hemispheres, hypothalamus,

cerebellum, and brainstem. The second patient presented first

with cutaneous lesions characteristic of Langerhans cell

histiocytosis. She subsequently developed bone abnormalities

suggestive of Chester-Erdheim disease, which was confirmed

by autopsy, raising the possibility of a common spectrum of

histiocytosis including both diseases. Gross examination of

the brain was normal, however, microscopy showed

infiltration of the brain by characteristic non-Langerhans cell

xanthogranulomas. The third patient presented with systemic

features characteristic of Chester-Erdheim disease.

Neurological signs included gait disturbance, seizures and

confusion. Examination of the brain did not show any

histiocytic infiltration, but did show changes suggestive of

Hallervorden-Spatz syndrome. Association of Chester-Erdheim

disease and Hallervorden-Spatz syndrome has not been

previously reported. The relationship between both conditions

is unclear.

4. Aiba, I.; Hashizume, Y.; Yoshida, M.; Okuda, S.; Murakami, N.;

Ujihira, N. Relationship between brainstem MRI and

pathological findings in progressive supranuclear palsy--study

in autopsy cases. J-Neurol-Sci. 1997 Nov 25; 152(2): 210-7;

ISSN: 0022-510X.

NETHERLANDS. The relationship between the features of MRI in

brainstem and pathological findings was investigated in eight

autopsy cases with progressive supranuclear palsy (PSP).

Features of T1-weighted images at midbrain level were

atrophy of tegmentum and tectum, and dilatation of aqueduct.

Histologically, these findings were consistent with atrophy of

periaqueductal gray matter, quadrigeminal plate, and

tegmentum. In these lesions, we detected neuronal loss,

decrease in density of myelinated fibers, gliosis, rarefaction

of tissues, and tau-positive structures such as neurofibrillary

tangles (NFTs), glial fibrillary tangles (GFTs) and neuropil

threads. At pons level, atrophy of tegmentum, atrophy of

pontine base, and dilatation of prepontine cistern were found.

Tau-positive structures were observed not only in tegmentum

but also in pontine base. The density of the tau-positive

structure was closely related to the severity of atrophy.

Features of T2-weighted images were high intensity in the

periaqueductal lesion and tegmentum in pons. In these lesions,

severe histological findings were detected. The MRI features

in brainstem were closely related to the histological findings

as PSP.

5. Amagai, S. Time coding in the midbrain of mormyrid electric fish.

II. Stimulus selectivity in the nucleus exterolateralis pars

posterior. J-Comp-Physiol-A. 1998 Feb; 182(2): 131-43; ISSN:

0340-7594.

GERMANY. The anterior and posterior exterolateral nuclei (ELa

and ELp) of the mormyrid midbrain are thought to play a

critical role in the temporal analysis of the electric discharge

waveforms of other individuals. The peripheral

electroreceptors receiving electric organ discharges (EODs) of

other fish project through the brainstem to ELa via a rapid

conducting pathway. EODs, composed of brief, but stereotyped

waveforms are encoded as a temporal pattern of spikes. From

previous work, we know that phase locking is precise in ELa.

Here it is shown that evoked potentials recorded from ELp

show a similar high degree of phase locking, although the

evoked potentials last much longer. Single-unit recordings in

ELp reveal two distinct populations of neurons in ELp: type I

cells are responsive to voltage step functions, and not tuned

for stimulus duration; type II cells are tuned to a specific

range of stimulus durations. Type II cells are less responsive

than type I cells, tend to respond with bursts of action

potentials rather than with single spikes, have a longer

latency, show weaker time locking to stimuli, and are more

sensitive to stimulus polarity and amplitude. The stimulus

selectivity of type II cells may arise from convergence of type

I cell inputs. Despite the loss of rapid conduction between ELa

and ELp, analysis of temporal features of waveforms evidently

continues in ELp, perhaps through a system of labeled lines.. 0;

124-87-8.

6. Amodio, P.; Marchetti, P.; Del Piccolo, F.; Beghi, A.; Comacchio, F.;

Carraro, P.; Campo, G.; Baruzzo, L.; Marchiori, C.; Gatta, A. The

effect of flumazenil on subclinical psychometric or

neurophysiological alterations in cirrhotic patients: a double-

blind placebo-controlled study. Clin-Physiol. 1997 Sep; 17(5):

533-9; ISSN: 0144-5979.

ENGLAND. It is not yet clear if benzodiazepine receptor

ligands, implicated in the pathophysiology of hepatic coma,

also have a role in subclinical cognitive or neurophysiological

alterations in cirrhotic patients. Therefore, we carried out a

double-blind, placebo-controlled study to evaluate the

effectiveness of flumazenil, a benzodiazepine antagonist, on

brainstem auditory evoked responses and on the number

connection test in cirrhotic patients with subclinical

neurophysiological or cognitive alterations. Thirteen cirrhotic

subjects with subclinical neurophysiological or cognitive

alterations were studied. A total of 3 mg of flumazenil or

saline was infused intravenously. Before and after the

infusion, the number connection test was administered and

brainstem auditory evoked responses recorded. After 72 h,

patients were crossed over. Flumazenil did not influence

brainstem auditory evoked responses or the number connection

test. A screening test for benzodiazepines was negative in all

subjects. We conclude that benzodiazepine receptor ligands

have a negligible role, if any, in the pathophysiology of

subclinical neurophysiological or cognitive alterations of

cirrhotic patients.. 0; 0; 78755-81-4.

7. Anderson, C. W.; Nishikawa, K. C. The functional anatomy and

evolution of hypoglossal afferents in the leopard frog, Rana

pipiens. Brain-Res. 1997 Oct 17; 771(2): 285-91; ISSN: 0006-

8993.

NETHERLANDS. Previously, we suggested that afferents are

present in the hypoglossal nerve of the leopard frog, Rana

pipiens. The basis for this was behavioral data obtained after

transection of the hypoglossal nerve. These afferents

coordinate the timing of tongue protraction with mouth

opening during feeding. The goal of the present study was to

define anatomically these hypoglossal afferents in Rana

pipiens. Retrograde tracing was performed using horseradish

peroxidase, fluorescent dextran amines and neurobiotin. Data

show that the cell bodies of hypoglossal afferents are located

in the dorsal root ganglion of the third spinal nerve and enter

the brainstem through its dorsal root. The afferents ascend in

the dorsomedial funiculus and move laterally after they pass

the obex. They project in the granular layer of the cerebellum

and the medial reticular formation. The cervical afferents that

travel in this pathway are known to carry proprioceptive and

cutaneous sensory information. We hypothesize that the

presence of afferents in the hypoglossal nerve is a derived

characteristic of anurans, which has resulted from the re-

routing of afferent fibers from the third spinal nerve into the

hypoglossal nerve. The appearance of hypoglossal afferents

coincides with the morphological acquisition of a highly

protrusible tongue.. EC 1.11.1.-.

8. Anderson, C. W.; Nishikawa, K. C. The functional anatomy and

evolution of hypoglossal afferents in the leopard frog, Rana

pipiens. Brain-Res. 1997 Oct 17; 771(2): 285-91; ISSN: 0006-

8993.

NETHERLANDS. Previously, we suggested that afferents are

present in the hypoglossal nerve of the leopard frog, Rana

pipiens. The basis for this was behavioral data obtained after

transection of the hypoglossal nerve. These afferents

coordinate the timing of tongue protraction with mouth

opening during feeding. The goal of the present study was to

define anatomically these hypoglossal afferents in Rana

pipiens. Retrograde tracing was performed using horseradish

peroxidase, fluorescent dextran amines and neurobiotin. Data

show that the cell bodies of hypoglossal afferents are located

in the dorsal root ganglion of the third spinal nerve and enter

the brainstem through its dorsal root. The afferents ascend in

the dorsomedial funiculus and move laterally after they pass

the obex. They project in the granular layer of the cerebellum

and the medial reticular formation. The cervical afferents that

travel in this pathway are known to carry proprioceptive and

cutaneous sensory information. We hypothesize that the

presence of afferents in the hypoglossal nerve is a derived

characteristic of anurans, which has resulted from the re-

routing of afferent fibers from the third spinal nerve into the

hypoglossal nerve. The appearance of hypoglossal afferents

coincides with the morphological acquisition of a highly

protrusible tongue.. EC 1.11.1.-.

9. Aouda, A.; Hayashi, F.; Fukuda, Y.; Masuda, Y. An in vitro

brainstem-heart preparation of the neonatal rat with intact

right vagus nerve. Jpn-J-Physiol. 1997 Oct; 47(5): 443-8; ISSN:

0021-521X.

JAPAN. An in vitro brainstem preparation of the neonatal rat

with intact right vagal (X) innervation of the right atrium, and

intact medullary roots of the left X and glossopharyngeal (IX)

nerves for stimulation was developed. The preparation was

continuously superfused with artificial CSF at 25 degrees C.

The electrical activity of the right atrium was recorded to

determine the heart rate. Applications of atropine or

propranolol to the superfusate did not alter the heart rate.

Electrical stimulation (0.5 ms pulse, 20 Hz) of the left IX and X

afferents elicited a reduction in the heart rate from 70.3 +/-

13.2 to 50.6 +/- 13.2 beats/min (mean +/- SD, p < 0.05), which

was abolished after division of the right X or application of

atropine to the superfusing solution. A similar reflex

bradycardia was seen in a preparation with intact left vagal-

right atrium innervation during right IX and X afferent

stimulation. Cervical spinal cord transection affected neither

the baseline heart rate nor the magnitude of the reflex

bradycardia. Longitudinal sectioning of the medulla oblongata

in the mid-line down to the level of the posterior inferior

cerebellar artery abolished the heart rate response. After

bilateral cervical vagotomies, electrical stimulation (0.5 ms

pulse, 20 Hz, up to 100 microA) of the ventrolateral medulla

oblongata, lateral funiculus at C2 or intermediate nucleus of

the spinal cord at Th1-4 did not affect the heart rate. These

results indicate that the functions in the lower brainstem are

preserved in this preparation, at least in regard to the

generation of reflex bradycardia. The results also suggest that

the laterality of cardiac vagal innervation and sympathetic

innervation will develop during the postnatal period. This

preparation may be useful for the study of the central neuronal

network controlling the heart rate.. 0; 0; 51-55-8; 525-66-6.

10. Arslan, E.; Turrini, M.; Lupi, G.; Genovese, E.; Orzan, E. Hearing

threshold assessment with auditory brainstem response (ABR)

and ElectroCochleoGraphy (ECochG) in uncooperative children.

Scand-Audiol-Suppl. 1997; 46: 32-7; ISSN: 0107-8593.

DENMARK. Two-hundred-and-sixty uncooperative children (442

ears) performed auditory brainstem response (ABR) and

Electrocochleography (ECochG) in the same diagnostic session

under general anaesthesia, and the results obtained with the

two different methods were compared. A difference > or = 20

dB between the two methods was found in 134 ears (30.3%).

The presence of middle ear effusion and symptoms of a

possible central nervous system pathology were considered in

order to verify the evidence of a correlation between the

difference in ABR-ECochG results and these clinical

parameters. The presence of middle ear effusion was not

significantly correlated with differences > or = 20 dB (p =

0.1347). On the contrary, the presence of symptoms indicative

of a possible central nervous system (CNS) involvement was

significantly correlated with differences > or = 20 dB (p =

0.0000). ABR has to be considered the first choice in hearing

assessment strategy, either for screening or diagnosis.

However, the diagnosis of hearing loss only on the basis of the

presence or absence of wave V requires some care in case of

suspected central auditory pathway lesions. In these cases,

ECochG may be the only reliable diagnostic tool for hearing

assessment in uncooperative subjects.

11. Arvanitogiannis, A.; Flores, C.; Shizgal, P. Fos-like

immunoreactivity in the caudal diencephalon and brainstem

following lateral hypothalamic self-stimulation. Behav-Brain-

Res. 1997 Nov; 88(2): 275-9; ISSN: 0166-4328.

NETHERLANDS. Fos immunohistochemistry was used to stain

neurons in the caudal diencephalon, midbrain and hindbrain

driven by rewarding stimulation of the lateral hypothalamus

(LH). Increases in Fos-like immunoreactivity were most

pronounced ipsilateral to the site of stimulation and tended to

be confined within discrete structures such as the posterior

LH, arcuate nucleus, ventral tegmental area (VTA), central

gray, dorsal raphe, pedunculopontine area (PPTg), parabrachial

nucleus, and locus coeruleus. At least two of these structures,

the VTA and PPTg, have been implicated in medial forebrain

bundle self-stimulation.. 0.

12. Austin, A. R.; Pawson, L.; Meek, S.; Webster, S. Abnormalities of

heart rate and rhythm in bovine spongiform encephalopathy.

Vet-Rec. 1997 Oct 4; 141(14): 352-7; ISSN: 0042-4900.

ENGLAND. Heart rates of healthy cows and cows suspected of

having bovine spongiform encephalopathy were measured by

auscultation and by a portable cardiac monitor. Bradycardia

was demonstrated in suspect cases which were confirmed

histopathologically. Disturbances in cardiac rhythm were also

evident in some cases. Healthy cows deprived of food exhibited

bradycardia. The administration of pharmacological doses of

atropine indicated that bradycardia in BSE was mediated by

increased vagal influence, suggesting that the cardioinhibitory

reflexes in the caudal brainstem were functionally altered by

the disease.. 0; 51-55-8.

13. Austin, M. C.; Rhodes, J. L.; Lewis, D. A. Differential distribution

of corticotropin-releasing hormone immunoreactive axons in

monoaminergic nuclei of the human brainstem.

Neuropsychopharmacology. 1997 Nov; 17(5): 326-41; ISSN:

0893-133X.

UNITED-STATES. Corticotropin-releasing hormone (CRH) has

been implicated in a variety of physiological and behavioral

responses to stress, as well as in the pathophysiology of

certain psychiatric disorders. Although studies in rodents

support a neuromodulatory influence of CRH on monoamine

neurotransmission in a number of brain regions, little

information in available to support a similar role for CRH in

the human brain. The present study used immunocytochemistry

to characterize the anatomical organization of CRH-

immunoreactive axons in the human brainstem. Substantial

regional differences in the density and distribution of CRH-

immunoreactive axons were found in the dopamine-,

noradrenaline- and serotonin-containing cell body regions of

the human brainstem. Dense networks of CRH-immunoreactive

axons were found in the medial subnuclei of the ventral

mesencephalon and in the dorsolateral region of the locus

coeruleus. Moderate densities of CRH-positive fibers were

located in the median and dorsal raphe, whereas lower

numbers of CRH-labeled axons appeared in the substantia nigra

pars compacta. In addition, differences in CRH innervation

density were observed within each region. For example, the

dorsal tier of the substantia nigra contained a greater density

of CRH-labeled axons than the ventral tier. In all monoamine-

containing nuclei, CRH-labeled axons exhibited numerous

beaded varicosities and fine intervaricose segments. The

differential distribution of CRH-containing axons across these

human brainstem nuclei suggests that the influence of CRH on

monoamine function may be neurotransmitter-specific.. 50-

67-9; 51-61-6; 9015-71-8.

14. Baguley, D. M.; Beynon, G. J.; Grey, P. L.; Hardy, D. G.; Moffat, D. A.

Audio-vestibular findings in meningioma of the cerebello-

pontine angle: a retrospective review. J-Laryngol-Otol. 1997

Nov; 111(11): 1022-6; ISSN: 0022-2151.

ENGLAND. The aim of this study was the determination of the

incidence of symptoms of audio-vestibular dysfunction and of

abnormalities on audio-vestibular testing in patients found to

have a unilateral meningioma of the cerebello-pontine angle

(CPA). The case notes of 25 patients diagnosed with unilateral,

sporadic and histologically proven CPA meningioma were

retrospectively reviewed. The age range of this series was 31-

71 years, with a mean age of 50 years. Two patients were

male (eight per cent) and 23 were female (92 per cent). The

mean length of history was 44.7 months. The distribution of

tumour size was skewed toward larger tumours, with 15 cases

(60 per cent) having tumours with a maximum diameter

greater than 3.5 cm on imaging. Pure tone audiometry was

normal in five cases (20 per cent), and no patients exhibited

the high frequency sensorineural hearing loss that is

characteristic of vestibular schwannoma. Speech audiometry

was normal in 50 per cent of cases. Caloric testing was

abnormal in 77 per cent of the 18 cases tested, whilst

auditory brainstem responses (ABR) were abnormal in 100 per

cent of the 18 cases who had sufficient hearing for this test

to be possible. The presence of normal audiometry in patients

with a proven CPA lesion indicates that, if in a protocol for

investigation, asymmetry of hearing is mandatory then some

pathology will be missed. Any suspicion of a CPA lesion

warrants investigation even in the absence of hearing loss. The

investigation of choice for the identification of CPA lesions

has become magnetic resonance imaging (MRI). If this

technique is not available then this study indicates that ABR

is a suitable and sensitive investigation. It should be borne in

mind however that the data in this study has been derived from

a series of predominantly large tumours, and the sensitivity of

ABR to smaller CPA meningiomata may fall, as is the case for

vestibular schwannoma.

15. Bakchine, S.; Crassard, I.; Seilhan, D. Anosognosia for hemiplegia

after a brainstem haematoma: a pathological case [letter]. J-

Neurol-Neurosurg-Psychiatry. 1997 Nov; 63(5): 686-7; ISSN:

0022-3050.

ENGLAND.

16. Ballanyi, K.; Lalley, P. M.; Hoch, B.; Richter, D. W. cAMP-dependent

reversal of opioid- and prostaglandin-mediated depression of

the isolated respiratory network in newborn rats. J-Physiol-

Lond. 1997 Oct 1; 504( Pt 1): 127-34; ISSN: 0022-3751.

ENGLAND. 1. Membrane potential (Vm) and resistance (Rm) of

ventral respiratory group (VRG) neurons were measured in the

isolated brainstem-spinal cord from newborn rats during bath

application of the opioid receptor agonists fentanyl or [D-

Ala2, D-Leu5]-enkephalin (Ala-Leu-Enk) and of the

prostaglandin E1 (PGE1). 2. PGE1 (0.1-3 microM) and fentanyl

or Ala-Leu-Enk (1-50 microM) produced depression and, at

higher doses, block of inspiratory nerve activity and

respiration-related postsynaptic potentials. This apnoea was

associated with hyperpolarization and Rm fall in 25% of

thirty-two VRG neurons tested, whereas resting Vm and Rm

were not changed in the other cells. 3. The selective mu- and

delta-receptor blockers naloxonazine (10-20 microM) and

naltrindole (50-100 microM) antagonized the effects of 5

microM fentanyl and 50 microM Ala-Leu-Enk, respectively. 4.

Opioid- and PGE1-evoked respiratory depression was reversed

upon elevation of endogenous cAMP levels by stimulating

adenylyl cyclase with 100 microM forskolin, activating

dopamine D1 receptors with 50-100 microM 6-chloro-7,8-

dihydroxy-3-allyl-1-phenyl-2, 3,4,5-tetrahydro-1H-3-

benzazepine (6-chloro-APB) or preventing cAMP breakdown

with 50-100 microM isobutylmethylxanthine. 5. The results

indicate that opioid- or prostaglandin-induced respiratory

depression is due to a fall in cAMP levels in cells responsible

for generation of rhythm or providing a tonic drive to the

respiratory network. 6. We suggest that elevation of cAMP

levels is an effective antidote in neonates against such forms

of respiratory depression.. 0; 0; 0; 0; 0; 0; 28822-58-4; 60-

92-4; 745-65-3.

17. Bardoul, M.; Drian, M. J.; Konig, N. AMPA/kainate receptors

modulate the survival in vitro of embryonic brainstem cells.

Int-J-Dev-Neurosci. 1997 Oct; 15(6): 695-701; ISSN: 0736-

5748.

ENGLAND. This study aimed at analyzing the involvement of

(RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic

acid/kainate (AMPA/kainate) receptors in the survival of

cultured rat embryonic brainstem cells, dissociated on

embryonic day 14. The cell number was estimated after

pharmacological manipulation of the receptors by exposure to

agonists or antagonists. The developmental stage at the

moment of drug application was critical for cell survival. We

observed after 8 days in vitro a much stronger decrease in the

number of gamma-enolase-positive cells when the cultures

were treated for 3 days with the antagonist 6,7-

dinitroquinoxaline-2,3-dione (DNQX) starting on the day of

plating than when DNQX was added after 5 days in vitro.

Conversely, exposure to the agonists (RS)-2-amino-3-(3-

hydroxy-5-tri-fluoromethyl-4-isoxazolyl)-propion ic acid (T-

AMPA) or kainate for 3 days significantly reduced cell survival

only when the treatment was initiated after 5 days in vitro.

Survival of S-100-positive cells was not affected after

exposure to either agonists or antagonists. Neither agonist nor

antagonist treatment modified cell proliferation, as assessed

by 5-bromo-2'-deoxyuridine (BrdU) staining, suggesting that

the decrease in the number of gamma-enolase-positive cells is

essentially due to cell death. If some of the processes we

observed in vitro correspond to analogous events in vivo, then

exposure to excitatory amino acid receptor agonists or

antagonists at critical stages of embryogenesis may alter the

development of the central nervous system.. EC 4.2.1.11; 0; 0;

0; 0; 0; 59-14-3.

18. Barrett, T. G.; Bundey, S. E. Wolfram (DIDMOAD) syndrome. J-Med-

Genet. 1997 Oct; 34(10): 838-41; ISSN: 0022-2593.

ENGLAND. Wolfram syndrome (MIM 222300) is the association

of juvenile onset diabetes mellitus and optic atrophy, also

known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus,

Optic Atrophy, and Deafness). Patients present with diabetes

mellitus followed by optic atrophy in the first decade, cranial

diabetes insipidus and sensorineural deafness in the second

decade, dilated renal outflow tracts early in the third decade,

and multiple neurological abnormalities early in the fourth

decade. Other abnormalities include primary gonadal atrophy.

Death occurs prematurely, often from respiratory failure

associated with brainstem atrophy. Most patients eventually

develop all complications of this progressive,

neurodegenerative disorder. The pathogenesis is unknown, but

the prevalence is 1 in 770000 in the UK and inheritance is

autosomal recessive. A Wolfram gene has recently been

mapped to chromosome 4p16.1, but there is evidence for locus

heterogeneity, and it is still possible that a minority of

patients may harbour a mitochondrial genome deletion. The

best available diagnostic criteria are juvenile onset diabetes

mellitus and optic atrophy, but there is a wide differential

diagnosis which includes other causes of neurodegeneration.

19. Basar, R.; Sargon, M. F.; Tekdemir, Y.; Elhan, A. The marginal

mandibular branch of the facial nerve. Surg-Radiol-Anat. 1997;

19(5): 311-4; ISSN: 0930-1038.

GERMANY. The peripheral, extraparotid course and localisation

of the marginal mandibular branch of the facial n. is described,

with variations, based on the dissection of 40 cadaver half

heads. Its anatomical relationships with the ramus of

mandible and facial a. are studied and morphometric features

are reported. Knowledge of the accurate course and

relationship of the marginal mandibular branch should help to

protect this nerve from surgical injury.

20. Bayliss, D. A.; Viana, F.; Talley, E. M.; Berger, A. J.

Neuromodulation of hypoglossal motoneurons: cellular and

developmental mechanisms. Respir-Physiol. 1997 Nov; 110(2-

3): 139-50; ISSN: 0034-5687.

NETHERLANDS. Hypoglossal motoneurons (HMs) in the caudal

brainstem have a respiratory-related activity pattern and

contribute to control of upper airway resistance. In this

review, we focus primarily on signalling mechanisms utilized

by neurotransmitters to enhance HM excitability. In particular,

we consider: (1) the membrane depolarization induced by a

number of different putative transmitters [thyrotropin-

releasing hormone (TRH), serotonin (5-HT), norepinephrine

(NE)]; and (2) the inhibition of a calcium-dependent spike after

hyperpolarization (AHP) by 5-HT and its effect on firing

behavior. Potential functional consequences on HM behavior of

these different neurotransmitter effects is discussed. In

addition, we describe postnatal changes in transmitter effects

and suggest potential cellular mechanisms to explain those

developmental changes. Most of the data discussed are derived

from in vitro electrophysiological recordings performed in

preparations from neonatal and adult rats.

21. Becker, T.; Becker, G.; Seufert, J.; Hofmann, E.; Lange, K. W.;

Naumann, M.; Lindner, A.; Reichmann, H.; Riederer, P.; Beckmann,

H.; Reiners, K. Parkinson's disease and depression: evidence for

an alteration of the basal limbic system detected by

transcranial sonography. J-Neurol-Neurosurg-Psychiatry. 1997

Nov; 63(5): 590-6; ISSN: 0022-3050.

ENGLAND. OBJECTIVES: Depression is a frequent symptom in

Parkinson's disease. Compelling evidence suggests a role of

the brainstem in the control of mood and cognition. In patients

with unipolar depression transcranial sonography (TS) studies

have shown structural alteration of the mesencephalic

brainstem raphe which could suggest an involvement of the

basal limbic system in the pathogenesis of primary mood

disorders. The objective of the present study was to evaluate

whether a similar alteration could be found in depressed

patients with Parkinson's disease using TS. METHODS: Thirty

patients with Parkinson's disease and 30 age and sex adjusted

controls were examined by TS. Raphe echogenicity was rated

semiquantitatively. The severity of motor symptoms and

depression was rated using standard research instruments.

RESULTS: Raphe echogenicity was significantly reduced in

depressed patients with Parkinson's disease compared with

nondepressed patients with Parkinson's disease and control

subjects. Raphe echogenicity correlated negatively with

degree of motor impairment, and differences in raphe echo

between depressed and non-depressed patients with

Parkinson's disease were upheld when motor impairment was

controlled for. CONCLUSION: These preliminary findings

suggest that, as in unipolar depression, a morphological

alteration of the brainstem raphe might be involved in the

pathogenesis of depression in Parkinson's disease. This raphe

alteration may reflect involvement in the basal limbic system

in the pathogenesis of secondary depression. This concept is in

line with current knowledge on the pathogenesis of both

depression in Parkinson's disease and primary depressive

disorders.

22. Bereiter, D. A.; Bereiter, D. F.; Tonnessen, B. H.; Maclean, D. B.

Selective blockade of substance P or neurokinin A receptors

reduces the expression of c-fos in trigeminal subnucleus

caudalis after corneal stimulation in the rat. Neuroscience.

1998 Mar; 83(2): 525-34; ISSN: 0306-4522.

UNITED-STATES. Stimulation of the cornea activates neurons

in two distinct regions of the spinal trigeminal nucleus: at the

transition between trigeminal subnucleus interpolaris and

subnucleus caudalis and at the transition between trigeminal

subnucleus caudalis and the upper cervical spinal cord as

estimated by expression of the immediate early gene, c-fos. To

determine if receptors for substance P or neurokinin A,

neurokinin 1 and neurokinin 2 receptors, respectively,

contribute to the production of Fos-positive neurons in these

brainstem regions, receptor-selective antagonists were given

intracerebroventricularly 15 min prior to stimulation of the

cornea in anesthetized rats. The number of Fos-positive

neurons produced in superficial laminae at the trigeminal

subnucleus caudalis/cervical cord transition by application of

the selective small fiber excitant, mustard oil, to the corneal

surface was reduced by the neurokinin 1 receptor antagonist,

CP99,994 (5-100 nmol, i.c.v.) and the neurokinin 2 receptor

antagonist, MEN10,376 (0.01-1.0 nmol, i.c.v.). Combined

pretreatment with CP99,994 and the competitive N-methyl-D-

aspartate receptor antagonist, CPP, caused a greater reduction

in c-fos expression at the subnucleus caudalis/cervical cord

transition than after either drug alone suggesting interaction

between receptors for glutamate and substance P. Tachykinin

receptor antagonists did not reduce the number of Fos-positive

neurons produced at the subnucleus interpolaris/subnucleus

caudalis transition. The elevation in plasma concentration of

adrenocorticotropin, but not the increases in arterial pressure

or heart rate, evoked by corneal stimulation was prevented by

pretreatment with CP99,994 or MEN10,376 at doses lower

than those needed to reduce c-fos expression. The results

indicate that receptors for substance P and neurokinin A

contribute to the transmission of sensory input from corneal

nociceptors to brainstem neurons in trigeminal subnucleus

caudalis and to increased activity of the hypothalamo-

pituitary axis that accompanies acute stimulation of the

cornea.. 0; 0; 0; 0; 0; 0; 135306-85-3; 136982-36-0; 404-86-

4; 86933-74-6; 9002-60-2.

23. Bernstein Goral, H.; Diener, P. S.; Bregman, B. S. Regenerating and

sprouting axons differ in their requirements for growth after

injury. Exp-Neurol. 1997 Nov; 148(1): 51-72; ISSN: 0014-4886.

UNITED-STATES. After spinal cord injury at birth, axotomized

brainstem-spinal and corticospinal neurons are capable of

permanent regenerative axonal growth into and through a fetal

spinal cord transplant placed into the site of either a spinal

cord hemisection or transection. In contrast, if fetal tissue

which is not a normal target of the axotomized neurons

(embryonic hippocampus or cortex) is placed into a neonatal

spinal cord hemisection, brainstem-spinal serotonergic axons

transiently innervate the transplant, but subsequently

withdraw. The first set of experiments was designed to test

the hypothesis that after spinal cord transection, serotonergic

axons would cross the nontarget transplant, reach normal

spinal cord targets caudal to the transection, and gain access

to requisite target-derived cues, permitting permanent

maintenance. Surprisingly, after a complete spinal cord

transection, brainstem-spinal axons failed to grow into an

inappropriate target even transiently. These observations

suggest that the transient axonal ingrowth into nontarget

transplants may represent lesion-induced axonal sprouting by

contralateral uninjured axons. We have used double-labeling

with fluorescent dyes, to test directly whether axonal

sprouting of neurons which maintain collaterals to uninjured

spinal cord targets (1) provide the transient ingrowth of

brainstem-spinal axons into a nontarget transplant and (2)

contribute to permanent ingrowth into target-specific

transplants. Uninjured red nucleus, raphe nucleus, and locus

coeruleus neurons extend axons into the nontarget transplant

while maintaining collaterals to the host spinal cord caudal to

the transplant. The lesion-induced sprouting by uninjured

axons was also observed with a target-specific transplant.

Taken together, these studies suggest that sprouting and

regenerating axons may differ in their requirements for

growth after injury.. 0; 50-67-9.

24. Berrebi, A. S.; Spirou, G. A. PEP-19 immunoreactivity in the

cochlear nucleus and superior olive of the cat. Neuroscience.

1998 Mar; 83(2): 535-54; ISSN: 0306-4522.

UNITED-STATES. We applied antiserum to PEP-19, a

presumptive calcium-binding polypeptide, to the auditory

brainstem of cats to determine whether this antiserum would

selectively reveal cochlear nucleus neurons and their

projections. We report that the entire populations of ventral

cochlear nucleus bushy and multipolar cells, but not octopus

cells, express this peptide in their somata and dendrites.

Presumed axons of spherical bushy cells located dorsally and

thicker globular bushy cell fibers located ventrally in the

trapezoid body are immunostained, as are thin fibers presumed

to represent the axons of multipolar cells. Large calyceal

endings in the medial nucleus of the trapezoid body are densely

immunoreactive as are smaller punctate profiles that outline

immunonegative neuronal profiles in the medial and lateral

superior olives. These features of immunolabeling indicate

that PEP-19 is expressed in all neuronal compartments. Within

the entire superior olivary complex, relatively few neurons are

immunolabeled, and the vast majority of these are found in the

periolivary nuclei. There are many more immunostained

neurons in lateral than in medial periolivary cell groups, but

their combined numbers are dwarfed by the numbers of

immunolabeled cells in the ventral cochlear nucleus. The

borders of the principal nuclei and some of the periolivary cell

groups are well defined by the distribution of PEP-19-

immunoreactive fibers and puncta. Since ventral cochlear

nucleus bushy cells comprise the predominant input to

principal nuclei of the superior olive, and the entire bushy cell

population is immunolabeled by PEP-19 antiserum, the

numbers and distribution of their inputs can be quantified. In

this study we report that immunoreactive puncta apposed to

the cell bodies and proximal dendrites of neurons in the medial

superior olive occur at a density of 20/100 microns2.

Moreover, we demonstrate by pre-embedding immunoelectron

microscopy that the PEP-19-immunoreactive punctate profiles

observed in the medial superior olive by light microscopy

represent presynaptic terminal boutons that contain round

synaptic vesicles and form asymmetric synaptic junctions,

features traditionally associated with excitatory synapses.

Thus, this antiserum represents a useful tool for investigating

the distribution of ventral cochlear nucleus fibers and

synaptic terminals within their target nuclei in the superior

olive.. 0; 106494-08-0.

25. Berridge, C. W.; Stratford, T. L.; Foote, S. L.; Kelley, A. E.

Distribution of dopamine beta-hydroxylase-like

immunoreactive fibers within the shell subregion of the

nucleus accumbens. Synapse. 1997 Nov; 27(3): 230-41; ISSN:

0887-4476.

UNITED-STATES. The nucleus accumbens (Acb) can be divided

into distinct subfields, delineated on the basis of

histochemical markers as well as by afferent and efferent

projection patterns. The shell subregion has reciprocal

relationships with a variety of limbic areas and brainstem

autonomic structures, and has been suggested to participate in

motivation-related processes, including reward, stress, and

arousal. The locus coeruleus (LC)-noradrenergic system has

similarly been implicated in the modulation of behavioral

state and stress-related processes, and previous studies have

demonstrated reciprocal projections between the locus

coeruleus and Acb shell. To better understand the anatomical

substrate through which LC could influence activity within

Acb shell, immunohistochemical methods were used to

visualize the extent and the distribution of noradrenergic

axons within this structure. Coronal sections of rat brain were

processed to visualize immunoreactivity for the

norepinephrine synthetic enzyme dopamine beta-hydroxylase

(DBH), a specific marker for noradrenergic processes. In some

cases, alternate sections were processed for

immunohistochemical localization of substance P, in order to

delineate core, shell, and pallidal compartments. Moderate-to-

dense DBH-like immunoreactivity (DBHir) was found in

approximately the caudal half of the shell subregion,

particularly in caudalmost (septal pole) and ventral zones. The

innervation of the septal pole was contiguous with a dense

innervation of the bed nucleus of the stria terminalis. Few

immunoreactive fibers were observed in the caudate-putamen,

Acb core, or rostral Acb shell. Many DBHir fibers within the

shell region were highly arborized with numerous varicosities,

features indicative of terminal fields. These observations

suggest noradrenergic systems might modulate certain

processes associated with stress, behavioral state, or

reinforcement via actions within the Acb shell.. EC 1.14.17.1;

33507-63-0; 51-41-2.

26. Bice, T. N.; Beal, J. A. Quantitative and neurogenic analysis of

neurons with supraspinal projections in the superficial dorsal

horn of the rat lumbar spinal cord. J-Comp-Neurol. 1997 Dec 1;

388(4): 565-74; ISSN: 0021-9967.

UNITED-STATES. Dual retrograde axonal tracers, Fluoro-Gold

(FG) and true blue (TB), were used in conjunction with

[3H]thymidine autoradiography to determine the number and

neurogenic pattern of neurons with supraspinal projections in

the superficial dorsal horn (SDH), i.e., laminae I and II, in

spinal segment L1 of the rat. FG was injected into rostral

brain centers (dorsal thalamus and midbrain), and TB was

injected into the caudal brainstem (medulla) in young adult

rats previously administered [3H]thymidine in utero. Following

stereological correction, each dorsal horn had an average of

1.22 neurons in lamina I and 0.24 neurons in lamina II that had

supraspinal projections per 10-microm transverse section. In

the SDH, 52% of the neurons with supraspinal projections were

found to project to rostral brain centers alone, 3.0% only to

the caudal brainstem, and 45% to both areas. There was no

significant difference in the percentage distribution of each of

the three groups of neurons between lamina I and lamina II.

Cell counts in the present study, in conjunction with previous

observations in the literature, suggest that the majority of

supraspinal projection neurons in the SDH fall into two groups:

1) spinomesencephalic neurons with collaterals to the medulla

and 2) spinothalamic neurons with collaterals to the midbrain.

The neurogenesis of supraspinal projection neurons in the SDH

proceeded along an axon-length gradient, whereby neurons

with the longest axons, those with projections to rostral brain

centers, completed neurogenesis prior to neurons with shorter

axons, those with projections only to the caudal brainstem.

The generation of all SDH neurons with supraspinal projections

was completed on embryonic day 14 (E14), 2 days prior to the

completion of neurogenesis for SDH neurons with intraspinal

projections.

27. Bodie, D.; Bennett Clarke, C. A.; Davis, K.; Postelwaite, J. P.;

Chiaia, N. L.; Rhoades, R. W. Organization, development, and

effects of infraorbital nerve transection on galanin binding

sites in the trigeminal brainstem complex. Somatosens-Mot-

Res. 1997; 14(3): 168-80; ISSN: 0899-0220.

ENGLAND. Previous experiments from this laboratory have

indicated that transection of the infraorbital nerve (ION, the

trigeminal [V] branch that supplies the mystacial vibrissae

follicles) at birth and in adulthood has markedly different

effects on galanin immunoreactivity in the V brainstem

complex. Adult nerve transection increases galanin

immunoreactivity in the superficial layers of V subnucleus

caudalis (SpC) only, while neonatal nerve transection results

in increased galanin expression in vibrissae-related primary

afferents throughout the V brainstem complex. The present

study describes the distribution of binding sites for this

peptide in the mature and developing V ganglion and brainstem

complex and determines the effects of neonatal and adult ION

damage and the associated changes in galanin levels upon their

distribution and density. Galanin binding sites are densely

distributed in all V brainstem subnuclei and are particularly

dense in V subnucleus interpolaris and the superficial layers

of SpC. They are present at birth (P-0) and their distribution is

similar to that in adult animals. Transection of the ION in

adulthood and examination of brainstem 7 days later indicated

marked reductions in the density of galanin binding sites in

the V brainstem complex. With the exception of the superficial

laminae of SpC, the same reduction in density remained

apparent in rats that survived > 45 days after nerve cuts.

Transection of the ION on P-0 resulted in no change in the

density of galanin binding sites in the brainstem after either 7

or > 60 days survival. These results indicate that densely

distributed galanin binding sites are present in the V

brainstem complex of both neonatal and adult rats, that they

are located in regions not innervated by galanin-positive

axons, and that their density is not significantly influenced by

large lesion-induced changes in the primary afferent content

of their natural ligand.. 0; 0.

28. Bogucki, J.; Gielecki, J.; Czernicki, Z. The anatomical aspects of a

surgical approach through the floor of the fourth ventricle.

Acta-Neurochir-Wien. 1997; 139(11): 1014-9; ISSN: 0001-

6268.

AUSTRIA. In 1993 Kyoshima et al. introduced safe entry zones

in the region of the 4th ventricle floor: infrafacial triangle and

suprafacial triangle. Is it possible to demarcate these zones

precisely in every case intra-operatively? A postmortem study

of 40 brainstems of patients who had died of non-brain

disease was performed to evaluate the degree of individual

morphological and morphometrical variability of the 4th

ventricle floor. The purpose of this study was to find constant

landmarks and distances within the rhomboid fossa region

which would help a neurosurgeon to determine safe approach

zones through the 4th ventricle floor to brainstem lesions.

Several anatomical landmarks-median sulcus, obex, vestibular

area, vagal triangle, hypoglossal triangle-were found to be

sufficiently visible in all examined brainstems. However, the

facial colliculus which is a border structure between the

infrafacial and suprafacial safe approach zone was poorly

visible in about 37% of the analyzed material. The striae

medullares were not found to be good orientation structures as

they were not visible in 30% of the material and exhibited

individual variability of a high degree in relation to their

number and arrangement. In the morphometrical study analyzed

measurements were taken by utilizing the digital image

analyzer MULTISCAN. Based on the results obtained the authors

suggest new borders of the infrafacial safe approach zone and

morphometrical directions to determine the suprafacial safe

approach zone in cases when the facial colliculus is not

clearly visible or invisible intra-operatively.

29. Bonaventure, P.; Voorn, P.; Luyten, W. H.; Jurzak, M.; Schotte, A.;

Leysen, J. E. Detailed mapping of serotonin 5-HT1B and 5-HT1D

receptor messenger RNA and ligand binding sites in guinea-pig

brain and trigeminal ganglion: clues for function. Neuroscience.

1998 Jan; 82(2): 469-84; ISSN: 0306-4522.

UNITED-STATES. The similar pharmacology of the 5-HT1B and

5-HT1D receptors, and the lack of selective compounds

sufficiently distinguishing between the two receptor

subtypes, have hampered functional studies on these receptors.

In order to provide clues for differential functional roles of

the two subtypes, we performed a parallel localization study

throughout the guinea-pig brain and the trigeminal ganglia by

means of quantitative in situ hybridization histochemistry

(using [35S]-labelled riboprobes probes for receptor

messenger RNA) and receptor autoradiography (using a new

radioligand [3H]alniditan). The anatomical patterns of 5-HT1B

and 5-HT1D receptor messenger RNA were quite different.

While 5-HT1B receptor messenger RNA was abundant

throughout the brain (with highest levels in the striatum,

nucleus accumbens, olfactory tubercle, cortex, hypothalamus,

hippocampal formation, amygdala, thalamus, dorsal raphe and

cerebellum), 5-HT1D receptor messenger RNA exhibited a more

restricted pattern; it was found mainly in the olfactory

tubercle, entorhinal cortex, dorsal raphe, cerebellum,

mesencephalic trigeminal nucleus and in the trigeminal

ganglion. The density of 5-HT(1B/1D) binding sites (combined)

obtained with [3H]alniditan autoradiography was high in the

substantia nigra, superior colliculus and globus pallidus,

whereas lower levels were detected in the caudate-putamen,

hypothalamus, hippocampal formation, amygdala, thalamus and

central gray. This distribution pattern was indistinguishable

from specific 5-HT1B receptor labelling in the presence of

ketanserin under conditions to occlude 5-HT1D receptor

labelling; hence the latter were below detection level.

Relationships between the regional distributions of the

receptor messenger RNAs and binding sites and particular

neuroanatomical pathways are discussed with respect to

possible functional roles of the 5-HT1B and 5-HT1D receptors..

0; 0; 0; 0.

30. Borday, V.; Fortin, G.; Champagnat, J. Early ontogeny of rhythm

generation and control of breathing. Respir-Physiol. 1997 Nov;

110(2-3): 245-9; ISSN: 0034-5687.

NETHERLANDS. The ability of central networks to produce

rhythmic motor behaviours linked to the respiratory function,

is a remarkably conserved property of the brainstem reticular

formation in vertebrates. Conserved cellular and molecular

mechanisms also underlie the early embryonic development of

the brainstem, leading to a segmented rhombencephalon in all

vertebrates. We have proposed that the neural network that

controls breathing after birth, derives from a primordial

rhythmic network first active in the segmented hindbrain of

the embryo. Observations on transgenic mice support this

hypothesis: homozygous inactivation of Krox-20, a gene

governing segmentation, leads to a lower-than-normal

respiratory frequency (fR), despite fetal maturation of the

respiratory network and functional compensatory control after

birth.

31. Bottai, D.; Dunn, R. J.; Ellis, W.; Maler, L. N-methyl-D-aspartate

receptor 1 mRNA distribution in the central nervous system of

the weakly electric fish Apteronotus leptorhynchus. J-Comp-

Neurol. 1997 Dec 8; 389(1): 65-80; ISSN: 0021-9967.

UNITED-STATES. We have isolated a partial cDNA for the N-

methyl-D-aspartate (NMDA) receptor 1 (NMDAR1) subunit from

an Apteronotus leptorhynchus brain cDNA library. The A.

leptorhynchus cDNA fragment, which corresponds to

nucleotides 135-903 within the 5' region of the rat NR1 mRNA,

encodes 252 amino acids that are >80% identical to the

homologous segments of the rat, human, and duck NR1 proteins.

RNAse protection assays revealed that the A. leptorhynchus

NR1 mRNA was highly enriched in the forebrain and

hypothalamus, with lesser amounts in the brainstem, and very

low levels in the cerebellum. In situ hybridization also

demonstrated that neurons in the pallial forebrain were highly

enriched in NR1 transcripts. High levels of NR1 mRNA were

found in pyramidal cells within the optic tectum and

octavolateral regions. Pyramidal cells of the electrosensory

lateral line lobe had the highest levels of expression, and the

NR1 mRNA was found to be selectively enriched in their apical

dendrites.. 0; 0; 9007-49-2.

32. Braune, S.; Hetzel, A.; Prasse, A.; Dohms, K.; Guschlbauer, B.;

Lucking, C. H. Stimulation of sympathetic activity by carbon

dioxide in patients with autonomic failure compared to normal

subjects. Clin-Auton-Res. 1997 Dec; 7(6): 327-32; ISSN: 0959-

9851.

ENGLAND. In vivo studies selectively assessing preganglionic

and central autonomic nervous system activity in patients

with autonomic failure have so far been limited to testing

pituitary function. In animal experiments carbon dioxide (CO2)

selectively stimulates central sympathetic nuclei in the

ventrolateral medulla and preganglionic sympathetic neurons

in the cervical trunk. This central stimulation seems to

overrule less pronounced peripheral vasodilatatory effects.

This study addressed the question of whether hypercapnea is a

suitable challenge procedure to test preganglionic and central

autonomic activity in healthy subjects and in patients with

autonomic failure of preganglionic and central origin. Seven

patients with multiple system atrophy (MSA) and 30 age-

matched healthy volunteers underwent a protocol including a

Valsalva manoeuvre (VM) under normo- and hypercapnic

conditions and exposure to hypercapnea under supine resting

conditions. Blood pressure (BP), heart rate (HR) and end-tidal

CO2 partial pressure were measured continuously and non-

invasively. In normal controls hypercapnea induced

significantly higher BP values in phases II, IIe, III and IV of

the VM compared to the normocapnic VM and a significant

increase in BP during steady-state supine exposure compared

to normocapnic baseline. HR increased significantly only after

40 s of steady-state hypercapnea during the latter challenge.

In patients with MSA and autonomic failure, in whom a

predominantly preganglionic lesion of the autonomic nervous

system is established, no significant effects of hypercapnea

on the cardiovascular parameters were found. Although this

non-invasive challenge procedure cannot differentiate between

pre- and postganglionic autonomic failure, exposure to

hypercapnea enables the investigation of efferent autonomic

activity to vasoconstrictors generated from autonomic centres

in the brainstem and cervical trunk.. 124-38-9.

33. Bredow, S.; Guha Thakurta, N.; Taishi, P.; Obal, F. Jr; Krueger, J. M.

Diurnal variations of tumor necrosis factor alpha mRNA and

alpha-tubulin mRNA in rat brain. Neuroimmunomodulation.

1997 Mar; 4(2): 84-90; ISSN: 1021-7401.

SWITZERLAND. The experiments described herein were

designed to determine whether tumor necrosis factor alpha

(TNF-alpha) displays a diurnal variation in various areas of the

normal rat brain. TNF-alpha mRNA transcripts were detected

by reverse-transcriptase polymerase chain reaction. To

monitor diurnal changes in TNF-alpha and alpha-tubulin

expression, rats were sacrificed every 4 h for 24 h starting 1

h after light onset; relative mRNA levels were determined for

the cerebellum, cortex, hippocampus, hypothalamus and

brainstem. TNF-alpha mRNA was higher during the light than in

the dark phase in the hypothalamus and hippocampus. alpha-

Tubulin mRNA exhibited a similar diurnal variation in the

hypothalamus, hippocampus and cortex. In contrast, beta-actin

mRNA was lower during the light phase than the dark phase in

the hippocampus and cortex. The observed diurnal variations in

TNF-alpha mRNA are consistent with the hypothesis that TNF

has a physiological role in the brain.. 0; 0; 0.

34. Bregman, B. S.; McAtee, M.; Dai, H. N.; Kuhn, P. L. Neurotrophic

factors increase axonal growth after spinal cord injury and

transplantation in the adult rat. Exp-Neurol. 1997 Dec; 148(2):

475-94; ISSN: 0014-4886.

UNITED-STATES. The capacity of CNS neurons for axonal

regrowth after injury decreases as the age of the animal at

time of injury increases. After spinal cord lesions at birth,

there is extensive regenerative growth into and beyond a

transplant of fetal spinal cord tissue placed at the injury site.

After injury in the adult, however, although host corticospinal

and brainstem-spinal axons project into the transplant, their

distribution is restricted to within 200 micron of the

host/transplant border. The aim of this study was to

determine if the administration of neurotrophic factors could

increase the capacity of mature CNS neurons for regrowth

after injury. Spinal cord hemisection lesions were made at

cervical or thoracic levels in adult rats. Transplants of E14

fetal spinal cord tissue were placed into the lesion site. The

following neurotrophic factors were administered at the site

of injury and transplantation: brain-derived neurotrophic

factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4),

ciliary-derived neurotrophic factor (CNTF), or vehicle alone.

After 1-2 months survival, neuroanatomical tracing and

immunocytochemical methods were used to examine the

growth of host axons within the transplants. The neurotrophin

administration led to increases in the extent of serotonergic,

noradrenergic, and corticospinal axonal ingrowth within the

transplants. The influence of the administration of the

neurotrophins on the growth of injured CNS axons was not a

generalized effect of growth factors per se, since the

administration of CNTF had no effect on the growth of any of

the descending CNS axons tested. These results indicate that

in addition to influencing the survival of developing CNS and

PNS neurons, neurotrophic factors are able to exert a

neurotropic influence on injured mature CNS neurons by

increasing their axonal growth within a transplant. Copyright

1997 Academic Press.. 0; 0; 0; 0; 0; 0; 143551-63-7; 50-67-

9.

35. Breitman, D. R.; Lee, S. S. Blunted responsiveness of the neuronal

activation marker Fos in brainstem cardiovascular nuclei of

cirrhotic rats. Hepatology. 1997 Dec; 26(6): 1380-5; ISSN:

0270-9139.

UNITED-STATES. Cardiovascular function in cirrhosis is

deranged, with indirect evidence of abnormal central

cardiovascular regulation. We aimed to elucidate the role of

brainstem cardiovascular nuclei in hemodynamic regulation by

examining the protein product, Fos, of the immediate-early

gene c-fos, in cirrhotic rats. Cirrhosis was induced by chronic

bile duct ligation (BDL) of 25-days duration, while controls

underwent a sham operation. To examine the effects of

jaundice per se in the absence of cirrhosis, a third group of 5-

day BDL rats was also studied. All rats were anesthetized with

pentobarbital, and catheters were inserted to measure

baseline blood pressure and heart rate. Separate groups were

then subjected to volume manipulation by a hypotensive

hemorrhage or isotonic saline infusion, or no challenge. Ninety

minutes after the volume manipulation, the animals were

killed and the medulla sectioned and stained for Fos by

immunohistochemisty. The nucleus tractus solitarius (NTS) of

the sham-operated unchallenged rats showed scant Fos

immunoreactivity (27.8 +/- 3.3 cells), but both hemorrhage and

volume infusion significantly increased Fos staining (86.0 +/-

3.7 and 95.2 +/- 8.5, respectively). In contrast, the

unchallenged cirrhotic rats showed markedly increased Fos in

the NTS (154.6 +/- 27.0), but neither hemorrhage nor volume

infusion significantly changed the amount of Fos staining. Fos

staining in the ventrolateral medulla (VLM) followed a similar

pattern with low staining in the unchallenged sham rats and

increased staining in the other groups, but no differences

between the unchallenged and the volume-manipulated

cirrhotic groups. The 5-day BDL jaundiced rats showed no

baseline increase in Fos staining, nor any significant increase

after hemorrhage. These results showing baseline activation

of central neuronal regions responsible for blood pressure

homeostasis, but completely blunted responsiveness in

cirrhotic rats, confirm a central origin of disordered

cardiovascular regulation. The presence of jaundice may also

contribute to the central cardiovascular hyporesponsiveness..

0.

36. Brodsky, M. C.; Fray, K. J. Brainstem hypoplasia in the Wildervanck

(cervico-oculo-acoustic) syndrome [letter]. Arch-Ophthalmol.

1998 Mar; 116(3): 383-5; ISSN: 0003-9950.

UNITED-STATES.

37. Brooks, P. J.; Kleopoulos, S. P.; Funabashi, T.; Mobbs, C. V.; Pfaff, D.

W. Widespread expression and estrogen regulation of PPEIA-3'

nuclear RNA in the rat brain. Proc-Natl-Acad-Sci-U-S-A. 1997

Dec 9; 94(25): 14037-41; ISSN: 0027-8424.

UNITED-STATES. We previously identified a novel nuclear RNA

species derived from the preproenkephalin (PPE) gene. This

transcript, which we have named PPEIA-3' RNA, hybridizes

with probes directed at a region of PPE intron A downstream

of an alternative germ-cell transcription start site, but does

not contain PPE protein coding sequences. We now report that

estrogen treatment of ovariectomized rats increases the

expression of conventional PPE heteronuclear RNA, and also

induces the expression of PPEIA-3' RNA, apparently in separate

cell populations within the ventromedial nucleus of the

hypothalamus. Further, we show that cells expressing PPEIA-3'

are found in several neuronal groups in the rat forebrain and

brainstem, with a distinct topographical distribution. High

densities of PPEIA-3' containing cells are found in the

reticular thalamic nucleus, the basal forebrain, the vestibular

complex, the deep cerebellar nuclei, and the trapezoid body, a

pattern that parallels the distribution of atypical nuclear

RNAs described by other groups. These results suggest that

this diverse neuronal population shares a common set of

nuclear factors responsible for the expression and retention of

this atypical RNA transcript. The implication of these results

for cell-specific gene transcription and regulation in the brain

and the possible relationship of PPEIA-3' RNA and other

atypical nuclear RNAs is discussed.. 0; 0; 0; 50-28-2; 63231-

63-0; 93443-35-7; 983-30-2.

38. Bucher, S. F.; Dieterich, M.; Seelos, K. C.; Brandt, T. Sensorimotor

cerebral activation during optokinetic nystagmus. A functional

MRI study. Neurology. 1997 Nov; 49(5): 1370-7; ISSN: 0028-

3878.

UNITED-STATES. Self-motion or object motion can elicit

optokinetic nystagmus (OKN), which is an integral part of

dynamic spatial orientation. We used functional MR imaging

during horizontal OKN to study cerebral activation patterns in

sensory and ocular motor areas in 10 subjects. We found

activation bilaterally in the primary visual cortex, the

motion-sensitive areas in the occipitotemporal cortex (the

middle temporal and medial superior temporal areas), and in

areas known to control several types of saccades such as the

precentral and posterior median frontal gyrus, the posterior

parietal cortex, and the medial part of the superior frontal

gyrus (frontal, parietal, and supplementary eye fields).

Additionally, we observed cortical activation in the anterior

and posterior parts of the insula and in the prefrontal cortex.

Bilateral activation of subcortical structures such as the

putamen, globus pallidus, caudate nucleus, and the thalamus

traced the efferent pathways of OKN down to the brainstem.

Functional MRI during OKN revealed a complex cerebral

network of sensorimotor cortical and subcortical activation.

39. Burkard, R.; Palmer, A. R. Responses of chopper units in the

ventral cochlear nucleus of the anaesthetised guinea pig to

clicks-in-noise and click trains. Hear-Res. 1997 Aug; 110(1-

2): 234-50; ISSN: 0378-5955.

NETHERLANDS. Auditory brainstem responses (ABRs) have been

measured with clicks, clicks masked by noise, click trains and

pseudorandom maximum length sequences (MLS) of clicks. To

investigate the neuronal populations contributing to the ABR

under these stimulation conditions, we measured the

extracellular responses of ventral cochlear nucleus (VCN)

units in the urethane-anaesthetised guinea pig. We studied 23

chopper, 7 primary-like and 7 onset units. This report focuses

on the responses from chopper units. The probability of

discharge for chopper units increased with increasing click

level reaching nearly 100% in many units, over a range of about

20-30 dB. Following each response to a click there was a 5-10

ms suppression of the spontaneous or noise evoked activity. As

the level of the noise was increased over a range of 20-30 dB,

the response to the clicks gradually decreased leading to a

complete abolition of the click response at high noise levels.

In a few units, low level noise produced a facilitation of the

response to single clicks. In response to constant level equally

spaced click trains, discharge probability increased with

increasing minimum pulse interval (MPI), approaching 100% for

MPIs of 4-8 ms in some units. The recovery afforded by the

gaps in the MLS train often resulted in higher discharge

probability for MLS than click trains with the same MPI, while

response probabilities for MLS and click trains were similar

when compared at equivalent average click rates. At short

MPIs (0.5 and 1.0 ms), peri stimulus time histograms in

response to click trains resembled those to best frequency

(BF) tones and noisebursts, with chopping peaks unrelated to

unit BF. VCN units show highly synchronised and reliable

responses to click trains, MLS trains and clicks masked by

noise. The decrease in discharge rate and increase in latency

of chopper units with decreasing click level, increasing click

rate and increasing masker level parallel the peak amplitude

and latency changes observed in the auditory brainstem

response.

40. Calore, E. E.; Cavaliere, M. J.; Calore, N. M. Cerebral amebiasis in

the acquired immunodeficiency syndrome. Acta-Neurol-Belg.

1997 Dec; 97(4): 248-50; ISSN: 0300-9009.

BELGIUM. Rare cases of cerebral amebiasis have been

described in AIDS patients. We report the case of a 46 year-old

homosexual man with AIDS who developed an intermittent

amnesia and a right palpebral ptosis. The cerebrospinal fluid

contained 169 cells (75% lymphocytes). The patient died five

days after hospitalization. Necropsy revealed thrombosis of

small vessels of the periventricular regions as well as

necrosis and hemorrhage of the periventricular tissue,

cerebellum and brainstem. The inflammatory process was

scarce and composed mainly of CD-68 positive macrophages. In

these regions as well as in meninges there were many

trophozoites of ameba of the Acanthamoeba group. Although

cerebral amebiasis is rare even in AIDS, the clinician should

be attentive to this diagnosis in patients with an insidious

encephalitis and cerebral cognitive abnormalities, with or

without focal motor signs.

41. Camuscu, H.; Dujovny, M.; Abd, el Bary T.; Beristain, X.; Vinas, F. C.

Microanatomy of the perforators of the anterior

communicating artery complex. Neurol-Res. 1997 Dec; 19(6):

577-87; ISSN: 0161-6412.

ENGLAND. We describe the microanatomy of the perforating

arteries arising from the anterior communicating artery

complex (5 mm distal of the anterior cerebral artery, the

anterior communicating artery, and 5 mm proximal of the

distal anterior cerebral artery). Thirteen unfixed human brains

were used in this study. The origin and number of perforators

are described, as is the site of brain penetration, and results

are correlated with previous studies. The hemodynamics of

blood flow in relation to the formation of an anterior

communicating artery aneurysm and different surgical

approaches are mentioned. The neuropsychological outcome

after aneurysm clipping with regards to the pattern of blood

supply from the anterior cerebral artery complex is also

discussed.

42. Cendes, F.; Andermann, F.; Dubeau, F.; Matthews, P. M.; Arnold, D. L.

Normalization of neuronal metabolic dysfunction after surgery

for temporal lobe epilepsy. Evidence from proton MR

spectroscopic imaging. Neurology. 1997 Dec; 49(6): 1525-33;

ISSN: 0028-3878.

UNITED-STATES. Surgery is a safe and effective treatment for

patients with temporal lobe epilepsy (TLE) who do not respond

adequately to anticonvulsant medication and in whom the

seizure generator can be identified and safely removed. Proton

MR spectroscopic imaging (MRSI) can image and quantify

neuronal damage in patients with TLE based on reduced signals

from N-acetylaspartate (NAA), a compound localized

exclusively in neurons. We performed proton MRSI in patients

with TLE before and after surgical treatment to determine

whether NAA or other resonance intensities changed in the

temporal lobes of patients with TLE after surgery, and

whether these changes correlated with surgical outcome. N-

acetylaspartate resonance intensity relative to creatine

(NAA/Cr) was abnormally low preoperatively in at least one

temporal lobe in all 14 patients examined. It was low

ipsilaterally in the patients who became seizure free and

bilaterally in those who did not. Postoperatively, it increased

to the normal range on the side of surgery in all patients who

became seizure free. In the one patient who became seizure

free and who had low NAA/Cr in both temporal lobes before

surgery, NAA/Cr values in the contralateral, unoperated

temporal lobe also increased to the normal range. In contrast,

NAA relative intensity ratios did not change in those patients

who continued to have seizures after surgery. The creatine

resonance intensity (Cr) in the temporal lobes was high,

relative to the brainstem, in seven patients preoperatively.

After surgery, the Cr remained high in two patients, both of

whom continued to have seizures. We conclude that NAA (and

Cr) abnormalities in TLE do not result solely from neuronal

loss and gliosis but can be reversible after postsurgical

control of seizures. This implies that the NAA and Cr

abnormalities in patients with TLE, at least in part, are

dynamic markers of both local and remote physiologic

dysfunction associated with ongoing seizures.. 0; 56-84-8;

57-00-1; 62-49-7; 997-55-7.

43. Chauhan, S.; Kochar, D. K.; Solanki, B. S.; Kumawat, B. L. Brainstem

auditory evoked potentials (BAEPs) and somatosensory evoked

potentials (SEPs) in enteric encephalopathy (EE).

Electromyogr-Clin-Neurophysiol. 1997 Oct; 37(7): 423-9; ISSN:

0301-150X.

BELGIUM. BAEPs and SEPs were studied in 25 patients of

enteric encephalopathy in acute phase and the results were

compared with 25 healthy control persons. In the study the

important observations of BAEPs were delayed peak latency of

wave III, wave V and delayed ILP I-V, and of SEPs was

prolonged peak latency of N20. The electrophysiological

evidence suggests metabolic cause for the coma and the SEP

changes were similar to those observed in cerebral malaria

reported earlier in this laboratory.

44. Cheng, J. D.; Espinosa, de los Monteros A; de Vellis, J. Glial- and

fat-specific expression of the rat glycerol phosphate

dehydrogenase-luciferase fusion gene in transgenic mice. J-

Neurosci-Res. 1997 Oct 15; 50(2): 300-11; ISSN: 0360-4012.

UNITED-STATES. Glycerol phosphate dehydrogenase (GPDH) is a

metabolic enzyme that catalyzes the conversion of

dihydroxyacetone phosphate to glycerol-3-phosphate. It

provides phospholipid precursors for lipid biosynthesis and

energy metabolism. In the brain, GPDH enzymatic activity,

protein, mRNA are exclusively associated with

oligodendroglial and Bergmann glial cells. Expression of GPDH

in the brain increases dramatically during the active period of

myelination, and is regulated by extracellular signals. In an

effort to understand the mechanism that confers glial-

specific expression of GPDH, we have examined the role of the

5' flanking sequence of the rat GPDH gene in conferring cell-

specific expression of reporter gene in transgenic mice.

Luciferase reporter constructs containing either the full-

length GPDH 5' flanking region (p4.3), or a distally truncated

version (p2.6), were injected into mouse zygotes. Three

independent lines of transgenic mice containing the p4.3, and

seven lines of mice containing the p2.6 constructs, were

analyzed. Luciferase enzyme activity was detectable only in

brain and fat, not in other GPDH-positive organs such as liver,

muscle, and kidney. Both the full-length and the distally

deleted transgenes were expressed similarly in these two

organs, indicating that the distal portion of the 5' flanking

region was not required for brain- and fat-specific expression.

Immunocytochemical analyses revealed that luciferase

immunoreactivity colocalized with glial fibrillary acidic

protein (GFAP)-positive Bergmann glia in the cerebellum, and

myelin basic protein (MBP)-positive oligodendroglia in the

cerebral cortex and the brainstem. Results here suggest that

the rat GPDH 5' flanking region directs glial-specific

expression of GPDH transcription in the brain, and provide a

good model for analyses of changes in glial metabolism in

response to extracellular perturbations in vivo.. EC 1.1.-; EC

1.13.12.-.

45. Chu, N. S.; Yang, S. S.; Liaw, Y. F. Evoked potentials in liver

diseases. J-Gastroenterol-Hepatol. 1997 Oct; 12(9-10): S288-

93; ISSN: 0815-9319.

AUSTRALIA. Evoked potentials are objective and quantitative

methods capable of evaluating functions of both peripheral and

central nervous systems (PNS and CNS). During the past 8

years, we have been using somatosensory, brainstem auditory,

and pattern-reversal visual evoked potentials (SEP, BAEP, VEP)

to study hepatic encephalopathy (HE) as well as functional

status of the PNS and CNS in various liver diseases including

viral hepatitis B, alcoholic liver disease and Wilson's disease

(WD). In HE irrespective of its etiologies, there is a sequential

prolongation and eventual disappearance of cortical

components of the median nerve evoked SEP while there is no

change in BAEP, suggesting that HE is primarily due to a

disturbance in cerebral cortical function and that median SEP

may be used for early detection of HE and for monitoring its

clinical course. In addition, absence of the N20-P25

component, or presence of only the N20 component of the wave

complex in fulminant hepatic failure is associated with high

mortality, whereas presence of late cortical components in HE

is usually associated with reversibility of clinical course.

Central conduction time (CCT) of the BAEP is prolonged in

patients with WD, alcoholic liver disease and liver cirrhosis

due to hepatitis B. Furthermore, BAEP abnormality is most

severe in WD, followed by alcoholic liver disease, and finally

hepatitis B. Peripheral nerve conduction as determined by the

N9 latency of SEP is slowed in alcoholic liver disease and liver

cirrhosis of chronic hepatitis B, but normal in WD. Our studies,

therefore, suggest that evoked potentials may be useful in the

evaluation of both CNS and PNS functions in various liver

diseases and also in the diagnosis and monitoring of HE.

46. Clark, J. L.; Moushegian, G.; Rupert, A. L. Interaural time effects on

the frequency-following response. J-Am-Acad-Audiol. 1997

Oct; 8(5): 308-13; ISSN: 1050-0545.

CANADA. Frequency-following responses (FFRs) were recorded

to evaluate differences between monaural and binaural

waveforms and waveforms evoked by stimuli with interaural

time disparities. Eight normal-hearing adult females served as

subjects. The stimuli were monaural and binaural 450-Hz

tonebursts at 65 and 60 dB SL and interaural time differences

of 0 and 660 microseconds, respectively. Normalized

amplitudes and periodicities of FFR waveforms within and

between subjects were compared. The results showed

asymmetric FFR to the various stimuli used in this study.

Binaural FFR waveforms were greater than monaural but

smaller than summed monaural FFRs. Binaural FFR amplitudes

evoked by a zero time difference were greater than amplitudes

evoked by a 660-microseconds difference. Additionally, tight

phase-locked periodicities were evoked in the FFR monaurally

and binaurally. The averaged FFR periodicity to all stimulus

conditions from all subjects was 2.29 msec, differing only 6.8

microseconds from the period of the 450-Hz stimulus. In

contrast, monaural and binaural neurons in the lower brain

stem typically exhibit much less synchroneities to low-

frequency tones than the FFR. These data provide evidence that

the FFR is not simply a sum of neuronal action potentials. The

findings suggest instead the presence of brainstem neuronal

networks. Such putative neuronal ensembles apparently

maintain a closer correspondence to the period of a low-

frequency sound, whether monaural or binaural, than the

discharge patterns of single neurons.

47. Colletti, V.; Fiorino, F. G.; Carner, M.; Tonoli, G. Mechanisms of

auditory impairment during acoustic neuroma surgery.

Otolaryngol-Head-Neck-Surg. 1997 Dec; 117(6): 596-605;

ISSN: 0194-5998.

UNITED-STATES. Hearing loss during removal of acoustic

neuroma (AN) may be due to labyrinthine and/or neural and/or

vascular damage. Surgical maneuvers relating to perioperative

and postoperative hearing may give rise to mechanisms of

auditory impairment. Recording action potentials from the

intracranial portion of the cochlear nerve (CN) has proven

particularly useful for identifying the mechanisms of

iatrogenic auditory injury. In this paper intraoperative and

postoperative auditory impairments are investigated in

relation to surgical steps in a group of 47 subjects with AN

(size ranging from 5 to 25 mm) undergoing removal by a

retrosigmoid-transmeatal approach. Drilling of the internal

auditory canal (IAC), removal of the AN from the IAC fundus,

coagulation close to the CN, lateral to medial tumor traction,

separation of the CN from the facial nerve, and stretching of

the CN have proven to be the most critical surgical steps in

hearing preservation. On the other hand, maneuvers such as

intracapsular tumor removal, vestibular neurectomy, suction

close to the AN, and closure of the IAC defect did not correlate

with changes in auditory potentials. Predisposing factors to

postoperative hearing deterioration were IAC enlargement

greater than 3 mm, IAC tumor size greater than 7 mm,

extracanalar tumor size greater than 20 mm, labyrinth medial

to the IAC fundus, severe involvement of the CN in the IAC,

preoperative abnormal auditory brainstem responses, and

normal vestibular reflectivity. Age and preoperative hearing

did not prove to be statistically related to postoperative

hearing. The variations in morphology and latency of CNAPs are

discussed in relation to the mechanisms of iatrogenic injury.

48. Colon, G. P.; Quint, D. J.; Dickinson, L. D.; Brunberg, J. A.; Jamerson,

K. A.; Hoff, J. T.; Ross, D. A. Magnetic resonance evaluation of

ventrolateral medullary compression in essential

hypertension. J-Neurosurg. 1998 Feb; 88(2): 226-31; ISSN:

0022-3085.

UNITED-STATES. OBJECT: The authors designed a blinded

prospective study comparing patients with essential

hypertension to patients without hypertension in which

magnetic resonance (MR) imaging was used to evaluate the role

of lateral medullary compression by adjacent vascular

structures as a cause of neurogenic hypertension. METHODS:

Patients with documented essential hypertension were

recruited to undergo thin-slice axial brainstem MR imaging

evaluation. Nonhypertensive (control) patients scheduled to

undergo MR imaging for other reasons also underwent thin-

slice MR imaging to form a basis for comparison. Magnetic

resonance images obtained in patients from the hypertensive

(30 patients) and the control (45 patients) groups were then

compared by four independent reviewers (two

neuroradiologists and two neurosurgeons) who were blinded to

the patients' diagnosis and hypertensive status. Images were

reviewed with regard to left versus right vertebral artery

(VA) dominance, compression of the medulla on the left and/or

right side, and brainstem rotation. Medullary compression was

graded as either vessel contact without associated brainstem

deformity or vessel contact with associated brainstem

deformity. CONCLUSIONS: There was a tendency toward left VA

dominance in the hypertensive group compared with the

control group, although a significant difference was shown by

only one of the four reviewers. There were no differences in

brainstem compression or rotation between the hypertensive

and nonhypertensive groups. These results are contrary to

those of recently published studies in which MR imaging

and/or MR angiography revealed lateral brainstem vascular

compression in hypertensive patients but not in

nonhypertensive (control) patients. Reasons for this

discrepancy are discussed. On the basis of their own

experience and that of others, the authors believe that

neurogenic hypertension does exist. However, thin-slice MR

imaging may not be a reliable method for detecting

neurovascularly induced essential hypertension and the

prevalence of neurovascular compression as the source of

hypertension may be overestimated when using current

imaging techniques.

49. Comi, G. Evoked potentials in diabetes mellitus. Clin-Neurosci.

1997; 4(6): 374-9; ISSN: 1065-6766.

UNITED-STATES. Abnormalities of central afferent and

efferent pathways have been revealed by evoked potential

studies in diabetic patients. Central conduction time is only

slightly prolonged; in afferent pathways the primary sensory

neuron is more affected than in the subsequent stages,

probably as an expression of a central-peripheral distal

axonopathy. Central nervous system abnormalities are more

frequent in patients with peripheral neuropathy, but evoked

potential can be abnormal even in patients without neuropathy.

Brainstem auditory evoked potential (BAEP), somatosensory

evoked potentials (SEPs) and visual evoked potentials (VEPs)

can be affected together, but isolated abnormalities are more

frequently observed. Diffuse neuropathological changes have

been found in the optic nerves, periventricular regions,

brainstem and spinal cord in postmortem pathological studies.

Similar changes have been found in animals with experimental

diabetes. The pathophysiology of central nervous system (CNS)

abnormalities is uncertain, many causes are probably active in

including neural damage: chronic hyperglycemia, hypoglycemic

episodes, angiopathy, blood-brain barrier dysfunction and

others, still unknown.

50. Cone Wesson, B.; Ramirez, G. M. Hearing sensitivity in newborns

estimated from ABRs to bone-conducted sounds. J-Am-Acad-

Audiol. 1997 Oct; 8(5): 299-307; ISSN: 1050-0545.

CANADA. This study focused on the problem of estimating

hearing sensitivity in newborns from auditory brainstem

responses (ABRs) evoked by clicks and 500 Hz and 4000 Hz

tonebursts presented by a bone-conduction (BC) oscillator. The

effects of acoustic energy transmitted to the ear canal,

gender, and ear differences were also investigated. ABR

thresholds for BC stimuli were 56, 52, and 53 dB (re 1 microN)

or -5, -14, and 0 dB nHL (re adult psychophysical threshold)

for click and 500 Hz and 4000 Hz tonebursts, respectively. For

newborns, ear canal SPLs generated by the BC stimuli were as

much as 21 dB greater than those in adults. Gender-related

threshold differences were significant, with female infants

having lower thresholds than males; however, ear differences

were not. The findings of this study can be used to set

appropriate BC stimulus levels for screening or assessment of

newborns.

51. Coplin, W. M.; Kim, D. K.; Kliot, M.; Bird, T. D. Mutism in an adult

following hypertensive cerebellar hemorrhage: nosological

discussion and illustrative case. Brain-Lang. 1997 Oct 1;

59(3): 473-93; ISSN: 0093-934X.

UNITED-STATES. Mutism after cerebellar injury has been

associated with tumors, hemorrhage, and surgery of midline

cerebellar structures. Literature review identified 54 cases,

primarily in children after surgical splitting of the inferior

vermis. We present a 47-year-old who developed transient

mutism after cerebellar hemorrhage. This represents the first

report of transient mutism in an adult with neither tumor nor

brainstem infarction and documents the importance of

cerebellar structures for initiation and production of speech in

adulthood. This case further differs from those previous

because of the long mute period and the subsequent return of

continued ataxic and dysarthric speech.

52. Couldwell, W. T.; Zhang, W.; Allen, R.; Arce, D.; Stillerman, C. B.

Cerebellar contusion associated with type I Chiari

malformation following supratentorial head trauma: case

report. Neurol-Res. 1998 Jan; 20(1): 93-6; ISSN: 0161-6412.

ENGLAND. Acute presentation of Type I Chiari malformation in

children is distinctly rare. An 11 year old male suffered a

trauma to the right temporal-parietal region in a tobogganing

accident resulting in an open depressed skull fracture.

Radiographic evaluation included a Computed Tomographic scan

which also demonstrated a significant cerebellar contusion

and the presence of subarachnoid hemorrhage in the region of

craniovertebral junction. Magnetic Resonance imaging revealed

an underlying Type I Chiari malformation. Somatosensory

evoked responses shortly following the injury demonstrated

slowing of conduction across the lower brainstem. The open

depressed fracture was debrided and elevated. Subsequent

observation resulted in slow improvement in neurological

function. A followup somatosensory evoked potential study

performed 21 days following the accident showed

improvement in conduction across the craniovertebral

junction. The tonsillar ectopia associated with Type I Chiari

malformation may predispose to cerebellar, upper spinal and

brainstem injury following supratentorial trauma.

53. Counter, S. A.; Buchanan, L. H.; Ortega, F.; Laurell, G. Normal

auditory brainstem and cochlear function in extreme pediatric

plumbism. J-Neurol-Sci. 1997 Nov 6; 152(1): 85-92; ISSN:

0022-510X.

NETHERLANDS. Lead (Pb) intoxication in children has been

associated with encephalopathy, sensory and cognitive

impairments. We investigated the prevalence and neuro-

sensory effects of Pb exposure in children living in Andean

villages of Ecuador with high Pb contamination from discarded

automobile batteries used in the local ceramics glazing

industry. Venous blood samples were collected from 107

children in the Pb glazing area and from 39 children living in a

geographically distant area with no known Pb contamination

and measured for blood lead (PbB) levels. Auditory brainstem

responses (ABR) and audiological/otological tests were

conducted on children in the Pb-Glazing Group. The median PbB

level for children in the Pb-Glazing Group was 40.0 microg per

dl (range: 6.2-128.2 microg per dl) and for the non Pb-Glazing

Group 6.0 microg per dl (1.9-18.0 microg per dl). The

differences in PbB levels for children in the study and control

areas were statistically significant (t-test, P<0.0001). ABR

tests on the Pb-Glazing Group indicated normal wave latencies

and neural transmission times, and no statistical correlation

between PbB level and interpeak latencies. Audiological tests

showed normal cochlear function and no statistical relation

between auditory thresholds and PbB level. Contrary to

prevailing assumptions, elevated PbB levels in children do not

invariably impair auditory brainstem neural transmission or

sensory-neural cochlear function, both of which have been

implicated as significant contributors to the

neurodevelopmental disabilities associated with childhood

plumbism.. 7439-92-1.

54. Crary, M. A.; Baldwin, B. O. Surface electromyographic

characteristics of swallowing in dysphagia secondary to

brainstem stroke. Dysphagia. 1997 Sep; 12(4): 180-7; ISSN:

0179-051X.

UNITED-STATES. Surface electromyography (SEMG) provides an

noninvasive avenue for evaluating swallowing physiology. This

report describes SEMG characteristics associated with

swallow attempts in 6 dysphagic patients who had suffered

brainstem stroke compared with 6 age and gender-matched

controls. Results indicated that patients with dysphagia

secondary to brainstem stroke differed in both amplitude and

timing aspects of swallowing attempts from asymptomatic

controls. Specifically, the results indicated that during

swallow attempts, dysphagic patients produced more muscle

activity over a shorter duration and with less coordination

than controls. Potential physiological mechanisms of these

results are discussed.

55. Cwik, V. A.; Hanstock, C. C.; Allen, P. S.; Martin, W. R. Estimation

of brainstem neuronal loss in amyotrophic lateral sclerosis

with in vivo proton magnetic resonance spectroscopy.

Neurology. 1998 Jan; 50(1): 72-7; ISSN: 0028-3878.

UNITED-STATES. In vivo proton magnetic resonance

spectroscopy (MRS) may be used to quantify brainstem

neuronal degeneration in ALS because of the neuronal

localization of N-acetylaspartate and N-

acetylaspartylglutamate, together termed NA, which are

estimated with this technique. We measured the ratio of NA to

creatine/phosphocreatine (NA/Cr) with proton MRS at 3.0 tesla

(T) in a 4.3-cm3 volume in the pons and upper medulla of 12

ALS patients and 17 age-matched control subjects. Brainstem

NA/Cr was reduced in ALS versus control subjects (mean +/-

SD: 1.57 +/- 0.20 versus 1.95 +/- 0.14; p < 0.0001). Patients

with severe spasticity or prominent bulbar weakness had the

lowest NA/Cr ratios; those with predominantly lower motor

neuron limb weakness had near-normal ratios. We conclude

that proton MRS may quantify region-specific neuronal

dysfunction in ALS.. 0.

56. Daniels, D. L.; Mark, L. P.; Ulmer, J.; Maas, E. F.; Borne, J. A.;

Calderwood, G. W. Understanding the brain stem. Neuroimaging-

Clin-N-Am. 1998 Feb; 8(1): 55-68; ISSN: 1052-5149.

UNITED-STATES. This article highlights features of brain

anatomy that are important to know in interpreting magnetic

resonance images. This article concentrates on the names of

some brain stem structures, the three-dimensional appearance

of six important tracts, and the location of cranial nerve

nuclei.

57. Darlington, D. N.; Tehrani, M. J. Blood flow, vascular resistance,

and blood volume after hemorrhage in conscious

adrenalectomized rat. J-Appl-Physiol. 1997 Nov; 83(5): 1648-

53; ISSN: 8750-7587.

UNITED-STATES. Hemorrhage leads to cardiovascular collapse

and death in adrenal-insufficient animals. To determine

whether the cardiovascular collapse is due to vasodilation

and/or failure to restore blood volume, we used radiolabeled

microspheres and 125I-labeled albumin to measure blood flow

and blood volume in conscious adrenalectomized (ADX) rats

after 15 ml.kg-1.3 min-1 hemorrhage. In ADX rats, hemorrhage

led to a greater fall than in sham rats in blood flow in the

stomach, small intestines, cecum, colon, spleen, hepatic portal

vein, kidney, testis, lung, thymus, bone, fat, forebrain,

cerebellum, and brainstem. The greater fall in blood flow was

caused by an increase in vascular resistance in these organs

except brain and hepatic artery. Sham rats maintained or

increased brain and hepatic artery blood flow after

hemorrhage whereas flow decreased and remained depressed in

ADX rats. ADX rats failed to restore blood volume, whereas

sham rats completely restored blood flow by 2 h. We conclude

that cardiovascular collapse in ADX rats does not result from

vasodilatation but may result from a failure to restore blood

volume. The failure to restore blood volume and the low blood

flow to organs, especially brain and liver, may contribute to

mortality in ADX rats after hemorrhage.

58. Dassesse, D.; Hemmens, B.; Cuvelier, L.; Resibois, A. GTP-

cyclohydrolase-I like immunoreactivity in rat brain. Brain-Res.

1997 Nov 28; 777(1-2): 187-201; ISSN: 0006-8993.

NETHERLANDS. GTPCH-I immunoreactive structures in the rat

brain were studied using a polyclonal antibody raised in the

chick. General mapping was made using the avidin-biotin-

peroxidase technique and compared with the distribution of

tyrosine hydroxylase and serotonin immunoreactivities. Double

immunofluorescence was performed in order to establish real

intracellular colocalization. GTPCH-I immunoreactivity was

generally found to be low. Immunostained neurons were

present in all the serotonin cell groups. In catecholaminergic

neurons, although tyrosine hydroxylase immunoreactivity was

always very high, GTPCH-I immunoreactivity was extremely

variable, from relatively strong (substantia nigra, ventral

tegmental area) to low (locus coeruleus, caudal part of the

hypothalamus), extremely low (rostral hypothalamus, ventral

brainstem) or almost absent (dorsal brainstem, some

hypothalamic nuclei). When feasible, double immunolabeling

revealed that all the serotonin cells and most of the tyrosine

hydroxylase cells were also expressing GTPCH-I. Our results

argue in favor of a regulation of tyrosine hydroxylase activity

by the intracellular synthesis of BH4.. EC 1.14.16.2; EC

3.5.4.16; 0; 17528-72-2; 22150-76-1; 50-67-9; 51-41-2.

59. Davies, A. M. Studies of neurotrophin biology in the developing

trigeminal system. J-Anat. 1997 Nov; 191( Pt 4): 483-91;

ISSN: 0021-8782.

ENGLAND. The accessibility of the primary sensory neurons of

the trigeminal system at stages throughout their development

in avian and mammalian embryos and the ease with which

these neurons can be studied in vivo has facilitated

investigation of several fundamental aspects of neurotrophin

biology. Studies of the timing and sequence of action of

neurotrophins and the expression of neurotrophins and their

receptors in this well characterised neuronal system have led

to a detailed understanding of the functions of neurotrophins

in neuronal development. The concepts of neurotrophin

independent survival, neurotrophin switching and neurotrophin

cooperativity have largely arisen from work on the trigeminal

system. Moreover, in vitro studies of trigeminal neurons

provided some of the first evidence that the neurotrophin

requirements of sensory neurons are related to sensory

modality. The developing trigeminal system has been studied

most extensively in mice and chickens, each of which has

particular advantages for understanding different aspects of

neurotrophin biology. In this review, I will outline these

advantages and describe some of the main findings that have

arisen from this work.. 0; 0.

60. Davis, M.; Walker, D. L.; Lee, Y. Amygdala and bed nucleus of the

stria terminalis: differential roles in fear and anxiety

measured with the acoustic startle reflex. Philos-Trans-R-

Soc-Lond-B-Biol-Sci. 1997 Nov 29; 352(1362): 1675-87; ISSN:

0962-8436.

ENGLAND. Neural stimuli associated with traumatic events

can readily become conditioned so as to reinstate the memory

of the original trauma. These conditioned fear responses can

last a lifetime and may be especially resistant to extinction. A

large amount of data from many different laboratories

indicate that the amygdala plays a crucial role in conditioned

fear. The amygdala receives information from all sensory

modalities and projects to a variety of hypothalamic and

brainstem target areas known to be critically involved in

specific signs that are used to define fear and anxiety.

Electrical stimulation of the amygdala elicits a pattern of

behaviours that mimic natural or conditioned states of fear.

Lesions of the amygdala block innate or conditioned fear and

local infusion of drugs into the amygdala have a