bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF ETHANOL ON THE CELLULAR COMPOSITION OF THE CEREBELLUM
Authors: BORGES S. , LEWIS P. D.
Published: May 2008

Borges S. & Lewis P.D. (1983) Neuropathology and Applied Neurobiology 9, 53–60

The effect of ethanol on the cellular composition of the cerebellum

Pregnant Wistar rats were fed on a diet of food pellets and a 10% (v/v) solution of ethanol in water during pregnancy and up to 21 days postnatally. Control groups were given food pellets and water ad libitum. Areal analysis of the cerebellum of neonates showed a significant reduction of 9–7% to 12–4% in three selected lobules of the mid‐sagittal vermis. Although there were no significant decreases in the linear frequency and absolute number of Purkinje cells, all three lobules showed a small percentage decrease in the length of Purkinje cell layer. The total number of granule cells was significantly reduced in all three lobules, and the ratio of granule cells to Purkinje cells was reduced by between 8–6% and 13–6%, although not significantly. The pyknotic index in the external granular layer (but not in the internal granular layer) was significantly increased at 21 days, while mitotic activity was unchanged. The extent of the diminution in the cell number of the internal granular layer suggests that besides increased cell death there may be a disturbance of cell proliferation kinetics in the precursor pool of the external granular layer. Although it is known that high blood levels can cause death of Purkinje cells, the moderate alcohol blood levels attained in this study were insufficient to do so.
THE MORPHOLOGICAL EFFECTS OF LEAD ON THE DEVELOPING CENTRAL NERVOUS SYSTEM
Authors: WINDER C. , GARTEN L. L. , LEWIS P. D.
Published: May 2008

Winder C, Garten L.L. & Lewis P.D. (1983) Neuropathology and Applied Neurobiology 9, 87–108

The morphological effects of lead on the developing central nervous system

The pathological changes found in the central nervous system of lead‐exposed humans and laboratory animals are reviewed. Data in man relate to relatively high exposure levels. In human childhood lead encephalopathy, which occurs with blood lead levels in the range 100–800 μg Pb/100 ml, oedema, vacuolation, haemorrhage and reactive glial changes appear to be secondary to microvascular lesions. No primary neuronal lesions have yet been clearly identified. Neurological signs and a pathological picture closely resembling that seen in human lead encephalopathy are obtained in young lead‐exposed rats with blood lead levels above 500 μg Pb/100 ml. Oedema and haemorrhage, cyst formation, reactive glial changes and nerve cell alterations are observed consequent to changes in capillary endothelial cells and basement membranes. High‐level lead exposure in rats also produces disturbances in myelinated axons and may affect neural network formation in the central nervous system. With intermediate lead levels (200–500 μg Pb/lOOml blood), vascular changes and their sequelae are not seen, but nutritional effects occur which may produce neuropathological changes. Data from recent studies on developing rats with low blood levels (up to 100 μg Pb/100 ml) appear to show effects of lead on maturing and differentiated nerve cell populations. The relevance of these changes to human subclinical lead intoxication remains to be seen. However, the overall correspondence of findings in lead‐poisoned man and rat would make further investigation in this area appear necessary.
ABNORMAL PERISOMATIC STRUCTURES IN NON‐PYRAMIDAL NEURONS IN THE CEREBRAL CORTEX IN DOWN'S SYNDROME
Authors: FABREGUES I. , FERRERf I.
Published: May 2008

Fabregues I. & Ferrer I. (1983) Neuropathology and Applied Neurobiology 9, 165–170

Abnormal perisomatic structures in non‐pyramidal neurons in the cerebral cortex in Down's syndrome

Abnormal fine filopodium‐like and stubby perisomatic processes are reported in stellate neurons, bipolar neurons and neurons with double dendritic arborization in the cerebral cortex of two patients with Down's syndrome. These findings suggest a more generalized abnormality in the development of receptor structures in Down's syndrome
CAN VIRAL ENVELOPE GLYCOLIPIDS PRODUCE AUTO‐IMMUNITY, WITH REFERENCE TO THE CNS AND MULTIPLE SCLEROSIS?
Authors: WEBB H. E. , FAZAKERLEY J. K.
Published: May 2008

Many viruses, with lipid envelopes derived from the host cell membranes, have been implicated in the aetiology of multiple sclerosis (MS), and epidemiological studies support an infectious agent. Alternatively the disease is thought by other workers to be auto‐immune in nature, and recently much attention has been focused on immunological sensitivity to glycolipids in MS patients. In this paper it is proposed that CNS demyelination could arise in susceptible individuals (HLA type) from an immune response to glycolipids, triggered by the carrier effect of one or more enveloped neurotropic viruses.
TULLIDORA (KARWINSKIA HUMBOLDTIANA) TOXIN MAINLY AFFECTS FAST CONDUCTING AXONS
Authors: HERNÁNDEZ‐CRUZ A. , MUÑOZ‐MARTÍNEZ E. J.
Published: May 2008

Cats were given a single oral dose of ether extracts from tullidora (Karwinskia hunboldtiana) fruit which contains an identified neurotoxin. Acute experiments were performed 4–7 weeks after toxin administration when flaccid limb paralysis was evident. Normal cats were used as controls. The medial gastrocnemius, the soleus and the sural nerves were electrically stimulated and the unitary potentials evoked by the stimuli were extracellularly recorded from spinal root filaments to measure the conduction velocity of single fibres. In control cats, the average conduction velocity (CV) was greater in medial gastrocnemius motor fibres than in the afferent ones of the same nerve and the soleus motor axons, whereas in the sural nerve CV was less than in the aforementioned cases. The CV values and the proportion of fast conducting fibres (> 80 m/s) in each nerve were directly related (r= 0.99). In treated cats, CV diminished in all the nerves studied, but the conduction velocity was further reduced in the faster fibres. Consequently, the motor division of the medial gastrocnemius nerve, normally composed of a high proportion (57%) of fast fibres, was more affected by tullidora and the sural nerve, which has the lowest proportion (0.7%) of these type of fibres, was the less affected. Our findings suggest that the preferential involvement of motor nerves in the experimental tullidora (buckthorn) neuropathy, as well as the preservation of somatic sensation in quadriplegic children accidentally poisoned with tullidora, are related to the distribution of axonal diameters in peripheral nerves.
THE EVOLUTION OF INTRACELLULAR RESPONSES TO ACRYLAMIDE IN RAT SPINAL GANGLION NEURONS
Authors: JONES H. B. , CAVANAGH J. B.
Published: May 2008

Acrylamide (30 mg or 50 mg/kg/day, 5 days each week) was injected intraperitoneally into rats for up to 4 weeks. Lumbar spinal ganglia, spinal cord and lumbrical muscle spindles were examined by light and electron microscopy at various times during this period. The first abnormalities in spinal ganglion neurons were seen at 7 days when an apparent increase in numbers of mitochondria, some being hypertrophic, were found in a few large light cells. This was 10 days before any significant Wallerian degeneration was found in muscle spindle sensory fibres. Mitochondrial changes became more marked with time and were later associated with RER disruption, loss of neurofilaments and peripheral displacement of the nucleus thus mimicking chromatolysis of the axon reaction. All these changes began, however, before axon degeneration. Evidence of increased satellite cell activity was maximal at 21 days. These changes are discussed in the light of the possibility that calcium entry into the cell may be seriously increased early in the intoxication as a direct result of the presence of acrylamide and that many of these cellular features are secondary responses to such an event. Distal degeneration of axons seems likely to be secondary to the perikaryal changes.
THE FUNCTION OF PERINEURONAL SATELLITE OLIGODENDROCYTES: AN IMMUNOHISTOCHEMICAL STUDY
Authors: LUDWIN S. K.
Published: May 2008

Perineuronal satellite oligodendrocytes in the mouse have been investigated immunocytochemically using antisera to myelin basic protein and myelin‐associated glycoprotein. In the normal animal, during remye‐lination, and following trauma the staining characteristics of these cells resembled those of other grey and white matter oligodendrocytes. It is concluded that these cells are, in many respects, functionally similar to other oligodendrocytes.
ACETYLCHOLINESTERASE ACTIVITY AND ITS FAST AXONAL TRANSPORT IN RABBIT SCIATIC NERVES DURING THE RECOVERY PHASE OF EXPERIMENTAL ALLERGIC NEURITIS
Authors: OIKARINEN RITVA , KALIMO HANNU
Published: May 2008

Acetylcholinesterase (AChE) activity and its fast axonal transport were studied in rabbit sciatic nerves with a double ligature system during the recovery phase of experimental allergic neuritis (EAN), 6‐9 days after the maximal symptoms, in order to obtain biochemical evidence of possible axonal damage in this primary demyelinating disease. The stationary AChE activity was significantly decreased, but the amount of the fast transported enzyme activity remained at the level of the controls. The velocity of the orthograde transport of AChE was slowed by about 15%, but this decrease was not statistically significant. Our results lend further support for the suggested neuronal damage in EAN, which can provide an explanation to the finding that the clinical symptoms in demyelinating diseases of the peripheral nervous system do not always correlate with the state of myelin.
A GOLGI STUDY OF CEREBELLAR ATROPHY IN HUMAN CHRONIC ALCOHOLISM
Authors: FERRER I. , FABREGUES I. , PINEDA M. , GRACIA I. , RIBALTA T.
Published: May 2008

When processed by the rapid Golgi method, a significant reduction (P < 0402) of the dendritic arborization of Purkinje cells located at the tips of the folia of the rostral vermis was demonstrated in four human cases of cerebellar atrophy, related to chronic alcohol consumption. Except for isolated damaged Purkinje cells located on the depth of the sulci of the rostral vermis in all but one case, no significant differences were observed between alcoholic cases and controls of comparable ages among Purkinje cells located in the remainder of the vermis or the cerebellar hemispheres. These results suggest that structural changes, which precede neuronal death and cell loss, are present in Purkinje cells of the rostral vermis in human cerebellar alcoholic degeneration.
EVOLUTION OF THE INTRACELLULAR CHANGES IN NEURONS CAUSED BY TRIMETHYLTIN
Authors: BROWN A. W. , CAVANAGH J. B. , VERSCHOYLE R. D. , GYSBERS M. F. , JONES H. B. , ALDRLDGE W. N.
Published: May 2008

Rats have been given a single dose of trimethyltin (10 mg/kg) and the intracellular events have been followed particularly in hippocampus, cerebral cortex, cerebellum and spinal ganglion cells. The earliest change visible occurs 12 h after this dose and is found to be dense membrane‐bound bodies, probably derived from branching tubulo‐vesicular smooth endoplasmic reticulum formations. These occur in close connection with rough endoplasmic reticulum and polyribosomes and appear also to have some association with the Golgi complex. At 24 h there is a general vacuolation of Golgi cisterns and SER membranes, and the membrane‐bound dense body formation is greatly increased. SER abnormalities are particularly conspicuous in Purkinje cells. In spinal ganglion cells, while vacuolation of Golgi cisterns is intense, dense bodies are inconspicuous and are replaced by increased autophagosomes, often of great complexity.

By 48 h vacuolation of Golgi cisterns has waned, but accumulation of dense bodies and secondary lysosomes has steadily increased. In spinal ganglion cells autophagosomes only are increased as the Golgi vacuolation declines. At later times steady increases of lysosomal dense bodies is seen generally accompanied in hippocampal pyramidal cells and dentate fascia cells by abundant cell death.

The suggestion is put forward that the Golgi complex may be the seat of the critical metabolic lesion and disturbances to protein transfer and protein synthesis follow. No explanation for the selective loss of hippocampal h1–5, (CA1‐CA4 except Sommer's sector) pyramidal cells and of small dentate fascia neurons can be derived from these conclusions.
EXPERIMENTAL BILATERAL CAROTID ARTERY OCCLUSION: A STUDY OF THE OPTIC NERVE IN THE RAT
Authors: TAKAMATSU J. , HIRANO A. , LEVY D. , HENKIND P.
Published: May 2008

Experimental bilateral carotid artery occlusion: a study of the optic nerve in the rat

The presence of marked changes in the neural retina and retinal vessels of Long‐Evans pigmented rat following bilateral carotid ligation has been previously documented by serial ophthalmologic examinations. Light and electron microscopic studies of the optic nerve in this experimental animal model revealed advanced optic nerve atrophy in ten of twelve rats examined. There was no significant pathology in either the retina or optic nerve in the remaining two rats after carotid ligation or in the sham‐operated controls.
A QUANTITATIVE HISTOLOGICAL STUDY OF NEURONAL LOSS FROM THE LOCUS COERULEUS OF AGEING MICE
Authors: STURROCK R. R. , RAO K. A.
Published: May 2008

A quantitative histological study of neurons in the locus coeruleus (LC) was carried out in ASH/TO mice aged 6, 9, 12, 15, 22, 25, 28 and 31 months. Counts were carried out on the right LC in 6 /xm parasagittal sections. There was a wide individual variation and also a variation between age groups from 6 and 15 months, but the mean number of neurons in the LC never fell below 1325 until after 25 months. The mean number of neurons in the LC from 6 to 25 months was 1520 ± 73. The mean number of neurons at 28 and 31 months was 1009 ± 60 and 854 ± 146 respectively. This indicates that the pattern of neuron loss in the LC of ASH/TO mice is similar to that found in the normal ageing human brain in a number of quantitative histological studies.
TWO TYPES OF BRAIN LESIONS IN WERNICKE'S ENCEPHALOPATHY
Authors: TORVIK> A.
Published: May 2008

Torvik A. (1984) Neuropathology and Applied Neurobiology 11, 179–190

Two types of brain lesions in Wernicke's encephalopathy

Analysis of 46 cases of Wernicke's encephalopathy showed that the pathological processes in the thalamus and inferior olives were clearly different from those in the mammillary bodies and the subependymal structures along the third and fourth ventricles and the aqueduct. The latter regions showed a progressive destruction of the neuropil with severe endothelial swelling and a definite sparing of the neurones. In the thalamus and inferior olives, by contrast, the reverse picture was found with neuronal disintegration, sparing of the neuropil, and a mild endothelial swelling. The disintegrating neurones in the thalamus and olives resembled those seen in anoxic necrosis. However, careful comparisons indicated a gradual drop out of the neurones in Wernicke's encephalopathy in contrast to the sudden and simultaneous affection of the neurones in anoxia. Furthermore, the nuclear structure of the affected neurones was better and longer preserved in the Wernicke lesions. The disintegrating neurones in Wernicke's disease were removed by neuronophagia and, in severe cases, the process led to a widespread neuronal loss in the thalamus and olives. The two types of histological processes largely paralleled each other in time and severity and it is suggested that they had the same aetiology.
ACRYLAMIDE‐INDUCED ASCENDING DEGENERATION OF LIGATED PERIPHERAL NERVE: EFFECT OF LIGATURE LOCATION
Authors: SHARER L. R. , LOWNDES H. E.
Published: May 2008

Sharer L. R. & Lowndes H. E. (1985) Neuropathology and Applied Neurobiology 11, 191–200

Acrylamide‐induced ascending degeneration of ligated peripheral nerve: effect of ligature location

Acrylamide was administered to rats for 10 days (50 mg/kg/day) after ligation of either proximal (sciatic) or distal (posterior tibial) nerves. Morphologic evaluation of the nerves revealed severe degeneration 0–5 cm proximal to the ligature, with progressively less pronounced change at successively higher levels above the ligature, when compared with ligated non‐treated controls. Although severe degeneration of the nerves was observed in both proximal‐ and distal‐ligated groups of animals, the distal‐ligated group showed slightly more change (at 0–5 cm above the ligature), suggesting a minor effect of distance of the site of nerve injury from the nerve cell body.
2,5‐HEXANEDIONE AND ACRYLAMIDE PRODUCE REORGANIZATION OF MOTONEURON PERIKARYA
Authors: STERMAN A. B. , SPOSITO N.
Published: May 2008

Sterman A. B. & Sposito N. (1985) Neuropathology and Applied Neurobiology 11, 201–212

2,5‐Hexanedione and acrylamide produce reorganization of motoneuron perikarya

During acrylamide and hexacarbon exposure few changes have been reported in motoneuron perikarya. In the present study, light microscopic examination of lumbar motoneurons from rats intoxicated with either 2,5‐hexanedione (2,5‐HD) or acrylamide showed relatively few nonspecific changes compared to controls. However, ultrastructural study of 2,5‐HD‐intoxicated perikarya revealed a range of cytological reorganization: nuclear eccentricity and capping, reduced numbers of large Nissl bodies, and mitochondrial hypertrophy and hyperplasia. In 2,5‐HD‐intoxicated perikarya, computer‐assisted stereologic analysis demonstrated a significant increase in the volume density of mitochondria, Ultra‐structurally, acrylamide‐intoxicated perikarya showed a marked reduction in the size of Nissl bodies. Stereologic analysis showed reductions in Nissl bodies, granular endoplasmic reticulum and Golgi complexes, and an increase in mitochondria. Taken together, these qualitative and morphometric changes, which were not obvious on light microscopic examination, imply significant reorganization of perikaryal metabolism.
PATHOGENESIS OF MOUSE SCRAPIE: DYNAMICS OF VACUOLATION IN BRAIN AND SPINAL CORD AFTER INTRAPERITONEAL INFECTION
Authors: COLE SHIRLEY , KIMBERLIN R. H.
Published: May 2008

Cole S. & Kimberlin R. H. (1984) Neuropathology and Applied Neurobiology 11, 213–227

Pathogenesis of mouse scrapie: dynamics of vacuolation in brain and spinal cord after intraperitoneal infection

At the late clinical stage of scrapie in mice, the severity and distribution of vacuolation in the brain (the lesion profile) is largely determined by the strain of agent and the genotype of the mouse: under controlled conditions, lesion profiles can be used to distinguish between scrapie strains. This paper describes the sequential development of lesions in brain at much earlier times and includes a study of spinal cord. Mice (CW) were infected intraperitoneally with 139A scrapie. Grey matter vacuolation first occurred in thoracic cord, developing later in lumbar and cervical cords, and then in various brain regions in a caudal to rostral sequence. This pattern closely matches the sequential spread of infection from mid‐thoracic cord to much of the CNS that was previously found in this scrapie model. Further studies of grey matter in spinal cord suggest that agent entered the mid‐thoracic region via sympathetic fibres. Vacuolation in white matter mirrored the grey matter pattern within an area but always occurred later. The severity of grey matter vacuolation in the four areas of the CNS where it developed early, reached plateau levels before the clinical stage of scrapie, but the severity was still increasing at the clinical stage in areas where vacuolation had started late. Hence the severity of lesions in a particular area may sometimes be limited by the time available for them to develop before the host dies. It appears that the distribution of vacuolation in this particular scrapie model is initially influenced by that of the infectious agent and only later does it reflect the distribution of vacuolation target areas shown by the characteristic lesion profile.
INTRACRANIAL MALIGNANT TERATOMA
Authors: DIENGDOH J. V. , BUXTON P. H. , FOY P. M.
Published: May 2008

Diengdoh J. V., Buxton P. H. & Foy P. M. (1985) Neuropathology and Applied Neurobiology 11, 245–250

Intracranial malignant teratoma

A case of malignant teratoma arising near the third ventricle in an adult is reported. It represented a true teratoma containing elements of all three germ layers of which two, namely the mesenchymal and endodermal elements have undergone malignant change. It was characterized by rapid recurrences after two operations with death occurring shortly after the second operation.
CEROID‐LIPOFUSCINOSIS (BATTEN'S DISEASE): PATHOGENESIS OF BLINDNESS IN THE OVINE MODEL
Authors: MAYHEW I. G. , JOLLY R. D. , PICKETT B. T. , SLACK P. M.
Published: May 2008

Mayhew I. G., Jolly R. D., Pickett B. T. & Slack P. M. (1985)

Neuropathology and Applied Neurobiology 11, 273–290

Ceroid‐lipofuscinosis (Batten's disease): pathogenesis of blindness in the ovine model

Blindness is a feature of the group of storage diseases of children known as the ceroid‐lipofuscinoses. Sequential studies in the ovine model, which most resembles the juvenile form of human disease, showed clearly that blindness had two components, a central and a peripheral. Whereas the central component, attributable to neuronal death and atrophy of the cerebral cortex, was responsible for early loss of vision, retinal atrophy was also extremely advanced in terminal stages of the disease. The primary retinal change was one of dystrophy of photoreceptor outer segments which preceded degeneration and necrosis of the photoreceptors cells themselves. Electroretinography showed that there was a progressive loss of a‐ and b‐waves during the course of the disease, but this was preceded by a diminished c‐wave which was eventually replaced by a negative potential. However, the pigment epithelium remained functionally (azide responsive) and ultrastructurally intact throughout the study. Loss of brain weight with selective cerebral atrophy also correlated with abnormal behaviour and facial manoeuvres that were intrepreted as partial seizures that did not become generalized.
THE CONTUSION INDEX: A REAPPRAISAL IN HUMAN AND EXPERIMENTAL NON‐MISSILE HEAD INJURY
Authors: ADAMS J. H. , DOYLE D. , GRAHMA D. I. , LAWRENCE A. E. , McLELLAN D. R. , GENNARELLI T. A. , PASTUSZKO M. , SAKAMOTO T.
Published: May 2008

Adams J. H., Doyle D., Graham D. I., Lawrence A. E., McLellan D. R., Gennarelli T. A., Pastuszko M. & Sakamoto T. (1985) Neuropathology and Applied Neurobiology 11, 299–308

The contusion index: a reappraisal in human and experimental non‐missile head injury

A previously described method of quantifying cerebral contusions in man (the contusion index) caused by non‐missile head injury has been modified and applied to a larger series of cases, and used to assess contusions in experimental head injuries. The initial findings in man have been confirmed, viz. that contusions are most severe in the frontal and temporal lobes; that contusions may be entirely absent in a patient dying as a result of a head injury; that there is no correlation between the severity of contusions and the nature of the injury; that the concept of contrecoup must continue to be questioned; that contusions are more severe in patients who have a fracture of the skull in comparison to those who do not; that contusions are more severe in patients who do not experience a lucid interval than in those who do; and that contusions are less severe in patients with diffuse axonal injury than in those who do not have diffuse axonal injury. The distribution of contusions in subhuman primates is similar to that seen in man, and they occur more frequently with short duration than with long duration acceleration.
CHANGES IN THE DISTRIBUTION OF HISTOCHEMICALLY LOCALIZED MERCURY IN THE CNS AND IN TISSUE LEVELS OF ORGANIC AND INORGANIC MERCURY DURING THE DEVELOPMENT OF INTOXICATION IN METHYLMERCURY TREATED RATS
Authors: HARGREAVES R. J. , FOSTER J. R. , PELLING D. , MOORHOUSE S. R. , GANGOLLI S. D. , ROWLAND I. R.
Published: May 2008

Hargreaves R. J., Foster J. R., Pelling D., Moorhouse S. R., Gangolli S. D. & Rowland I. R. (1985) Neuropathology and Applied Neurobiology 11, 383–401

Changes in the distribution of histochemically localized mercury in the CNS and in tissue levels of organic and inorganic mercury during the development of intoxication in methylmercury treated rats

The development of neurotoxicity in rats after exposure to methylmercuric chloride was monitored using behavioural indices. At selected time points the cellular localization of mercury and the relative amounts of organic and inorganic mercury were determined in several regions of the CNS, and in some non‐neural tissues. The CNS showed an affinity for organic mercury, the levels of inorganic mercury remaining low throughout symptomatic intoxication. Histopathological changes were not closely related to the regional tissue content of the organic or inorganic forms, nor to mercury localized histochemically at the cellular level. The stained deposits, which had focal cytoplasmic distribution, appeared in glial cells initially then in larger neurones as the intoxication progressed. These observations may represent changes in the mercury content of different cell types or reflect differences in the way that they handle a similar burden of mercury. A transitory accumulation of mercury in glial cells may be a factor contributing to the occurrence of a latent period and sequestration of mercury in cytoplasmic organelles may serve to protect some cell types from injury.
PROGRESSIVE AXONOPATHY: AN INHERITED NEUROPATHY OF BOXER DOGS. 2. THE NATURE AND DISTRIBUTION OF THE PATHOLOGICAL CHANGES
Authors: GRIFFITHS I. R. , McCULLOCH M. C. , ABRAHAMS S.
Published: May 2008

Griffiths I. R., McCulloch M. C. & Abrahams S. (1985) Neuropathology and Applied Neurobiology 11, 431–446

Progressive Axonopathy: an inherited neuropathy of boxer dogs. 2. The nature and distribution of the pathological changes

This report describes the neuropathology of progressive axonopathy (PA), an autosomal recessive inherited neuropathy of Boxer dogs, which affects CNS and PNS. The nerve roots contain numerous myelin bubbles and proximal paranodal axonal swellings containing vesicles, vesiculo‐tubular profiles and disorganized neurofilaments. The myelin sheath overlying such swellings is often attenuated. As the disease develops there are progressive changes in the myelin sheath with thinning at paranodal and internodal locations, loss of myelin from lengths of axon and the formation of short internodes with disproportionately thin sheaths. The abnormalities show a very definite selectivity for nerve roots and proximal nerves. Conversely, the frequency of degeneration and regeneration is greater distally except in the cervical ventral roots which contain numerous regenerating clusters. In the CNS numerous axonal spheroids are found in the lateral and ventral columns of the spinal cord and in various brain stem nuclei, particularly the superior olives, accessory cuneate nuclei and lateral lemniscus and its nucleus. Axonal degeneration which occurs mainly in the cord shows no obvious tract or proximal/distal selectivity. The optic pathways are also involved, predominantly adjacent to the chiasma. The autonomic nervous system is affected and distal limb muscles show varying, but usually minor, degrees of neurogenic atrophy. The condition, which has no obvious direct parallel in human or veterinary medicine, shows gross disturbances of axon‐glial interrelationships in both CNS and PNS.
TRANSMISSIBLE MINK ENCEPHALOPATHY (TME) IN CHINESE HAMSTERS: IDENTIFICATION OF TWO STRAINS OF TME AND COMPARISONS WITH SCRAPIE
Authors: KIMBERLIN R. H. , COLE SHIRLEY , WALKER CAROL A.
Published: May 2008

Kimberlin R. H., Cole S. & Walker C. A. (1986) Neuropathology and Applied Neurobiology 12, 197–206

Transmissible mink encephalopathy (TME) in Chinese hamsters: identification of two strains of TME and comparisons with scrapie

TME from a single source was transmitted by intracerebral injection to Chinese hamsters, producing clinical disease in all seven animals after incubation periods of over 600 days. The brain from each of the primary cases was used to establish separate intracerebral passage‐lines of TME and this led to the isolation of two different strains of agent, designated 333K and 333W. These strains were easily distinguished by the incubation periods they produced (about 130 and 230 days, respectively) under standard conditions of infection, and by the characteristic profiles of vacuolation seen in different regions of the brain. Comparisons were made with a strain of scrapie passaged in Chinese hamsters, designated 34W, which could be distinguished from both strains of TME. Nevertheless the properties of the scrapie and TME strains overlapped, with one of the TME strains (333K) resembling the 34W strain of scrapie in Chinese hamsters more closely than the other TME strain (333W). These similarities strengthen the view that TME and scrapie are caused by a similar type of infectious agent. The very large ‘species barrier effect’ on transmitting TME to Chinese hamsters was in marked contrast to the minimal effect seen with scrapie and an explanation for this is suggested. Two interesting pathological features of the study were (a) the severe loss of pyramidal cells produced in the hippocampus by the 34W strain of scrapie, and (b) the focal, symmetrical vacuolation of the thalamus caused by 333K TME.
THE TOPOGRAPHY OF PLAQUES AND TANGLES IN DOWN'S SYNDROME PATIENTS OF DIFFERENT AGES
Authors: MANN D. M. A. , YATES P. O. , MARCYNIUK B. , RAVINDRA C. R.
Published: May 2008

The topographical distribution of senile plaques and neurofibrillary tangles has been investigated in 12 patients with Down's syndrome ranging from 31 to 65 years of age. No plaques or tangles whatsoever were seen in the brain of the 31‐year‐old patient. The nine patients over 53 years of age, showed a similar pathological picture in which there were numerous mature plaques in all areas of cerebral cortex, hippocampus and amygdala and numerous tangles in these areas and in subcortical structures such as nucleus basalis, locus caeruleus, dorsal raphe, ventral tegmental area, substantia nigra, olfactory bulb and tracts. In the other two patients aged 37 and 51 years, an intermediate pathological picture was seen in which primitive plaques predominated within the cortex, with numerous mature plaques in hippocampus and amygdala. In the 37‐year‐old patient, tangles were numerous in the entorhinal cortex, but much less common in hippocampus and amygdala, rare in cerebral cortex and absent in the subcortical areas, olfactory bulbs and tracts. A similar pattern was seen in the 51‐year‐old patient though here some cells in the subcortex were also affected. These observations suggest that the primary focus of plaque and tangle formation in Down's syndrome may be in amygdala, entorhinal cortex and hippocampus, with a ‘spreading out’ to subsequently involve all areas of cortex, certain subcortical regions and the olfactory bulbs and tracts. It appears unlikely that the olfactory bulbs and tracts provide a portal of entry for any pathogenic agent that may be responsible for inducing plaque and tangle formation within the rest of the brain.
STRINGHALT IN HORSES: A DISTAL AXONOPATHY
Authors: CAHILL J. I. , GOULDEN B. E. , JOLLY R. D.
Published: May 2008

A detailed investigation of the neuropathology of a horse affected with stringhalt was performed. Qualitative and quantitative light and electron microscopy, and single teased fibre preparations of peripheral nerve demonstrated predominantly axonal degeneration, the stage of which was appropriate for the duration of clinical signs. There was selective involvement of large myelinated nerve fibres. A proximal to distal increase in the severity of pathological changes was present in the peripheral nerves. The long left recurrent laryngeal nerve was the most severely affected, followed in order by its right counterpart, the hindlimb and forelimb nerves. Neurogenic atrophy of muscles innervated by affected peripheral nerves also showed a distally graded increase in severity. No lesions were observed in the central nervous system. It was concluded that this disease should be classified as a distal axonopathy.
FIBROSARCOMA ARISING IN A LUMBOSACRAL MENINGOCOELE
Authors: SMITH C. M. L. , TIMPERLEY W. R.
Published: May 2008

A 53 year old woman presented with enlargement of a sacral meningocoele and pain in the back and legs. She died from a pulmonary embolus. Fibrosarcoma, apparently arising in the sacral region, involved the leptomeninges and nerve roots as far rostrally as the pons. Nine previously reported cases are discussed.
THE EFFECTS ON FETAL BRAIN DEVELOPMENT IN THE RAT OF A SEVERELY IODINE DEFICIENT DIET DERIVED FROM AN ENDEMIC AREA: OBSERVATIONS ON THE FIRST GENERATION
Authors: JIANQUN LI , XIN WANG , YUQUIN YAN , KEWEI WANG , DAKAI QIN , ZHENFU XIN , JUN WEI
Published: May 2008

The effects on fetal brain development in the rat of a severely iodine deficient diet derived from an endemic area: observations on the first generation

Rats were fed on a severely iodine deficient diet (iodine content 4.5 μg/100 g) similar to that being consumed by people living in a village with a high rate of endemic cretinism. After a period of 4 months, the thyroid and brain were studied in the adult and their fetuses at 16, 17, 18, 19 and 20 days of gestation, and in postnatal animals at 1, 5, 10, 20, 30 and 60 days of age. By comparison with a control group (diet with iodine content 54.7 μg/100 g) the experimental group showed marked goitres, a higher uptake of 125I by the thyroid, reduced serum T4, and reduction in brain weight. The cerebral and cerebellar histological findings showed that the density of brain cells had increased, and the mean neuron size was reduced. Furthermore, disappearance of the cerebellar EGL was delayed. These findings indicate that this animal model is likely to be suitable for the studies of endemic cretinism in man.
UNOCYTOCHEMICAL CHARACTERIZATION OF THE A15 A5 TRANSPLANTABLE BRAIN TUMOUR MODEL IN VIVO
Authors: SAGGU H. , PILKINGTON G. J.
Published: May 2008

Immunocytochemical characterization of the A15 A5 transplantable brain tumour model in vivo

A comparative immunocytochemical study was carried out on intracerebral and extracranial gliomas of the rat produced by intracerebral injection of low (10th) and high (40th) in vitro passages of neoplastic glial cells. The cells injected were a neoplastic astrocytic clone– A15 A5– derived from a mixed glioma induced transplacentally by N‐ethyl‐N‐nitrosourea (ENU) in a BD‐IX rat. An inverse relationship was seen between the expression of the astrocytic markers glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) at low and high passage: GFAP decreased with increasing passage while GS increased. The distribution of vimentin, the major cytoskeletal component of immature glia, was constant, irrespective of passage–a feature consistent with previous in vitro findings. The expression of laminin by both reactive and neoplastic astrocytes increased with increasing passage, while high magnification examination revealed the presence of the glycoprotein fibronectin on the cell‐surfaces of A15 A5‐derived tumour cells. Both neoplastic and reactive astrocytes expressed S‐100 protein with a higher proportion of positive cells in extracranial tumours. Occasional cells, probably actively phagocytozing populations of reactive astrocytes and macrophages, were positive for alpha‐1‐antitrypsin. None of the neoplastic cells expressed the oligodendrocyte marker carbonic anhydrase II. This immunocytochemical study supports previous morphological findings in differences in differentiation between the cells of tumours produced by high and low passage cells.
AN ULTRASTRUCTURAL ANALYSIS OF THE EFFECTS OF ACCUMULATION OF NEUROFIBRILLARY TANGLE IN PYRAMIDAL NEURONS OF THE CEREBRAL CORTEX IN ALZHEIMER'S DISEASE
Authors: SUMPTER P. Q. , MANN D. M. A. , DAVIES C. A. , YATES P. O. , SNOWDEN J. S. , NEARY D.
Published: May 2008

An ultrastructural analysis of the effects of accumulation of neurofibrillary tangle in pyramidal neurons of the cerebral cortex in Alzheimer's disease

Quantitative morphometric (stereological) methods have been used to assess the effects of accumulation of neurofibrillary material on the fine structure of pyramidal cells in biopsy specimens of temporal cortex from nine patients with Alzheimer's disease. When compared with non‐tangled cells from the same patients, tangled cells show an increase in total area of cytoplasm due to the accumulation of tangle and a reduction in the area of the nucleus; the area proportion of the cell body occupied by total cytoplasm, therefore, increases whereas that of the nucleus decreases. Within the total cytoplasm, nucleolar and mitochondrial areas are maintained, but that of lipofuscin is increased, though all are increased when expressed as a proportion of the useful cytoplasm alone (i.e. total cytoplasmic area minus area occupied by tangle). Measures of the amount of rough endoplasmic reticulum and ribosomes are decreased overall in tangled cells, though when related to useful cytoplasm alone such measures approach non‐tangled cell values. Measures of smooth endoplasmic reticulum are unaltered throughout. When related to the amount of tangle within cells it was found that the most heavily tangled cells retain 28% of useful cytoplasm, 72% of the nuclear area, 50% of the rough endoplasmic reticulum and 27% of ribosomes present within least tangled and non‐tangled cells. By contrast, mitochondrial area is maintained and that of lipofuscin increased. The capacity for protein synthesis in tangled cells appears, therefore, to be progressively decreased with accumulation of tangle, whereas that for oxidative metabolism is maintained and lysosomal activity, perhaps, increased. Neurofibrillary tangle formation and accumulation may, therefore, lead to the eventual death of neurons and be the major cause of nerve cell loss in Alzheimer's disease.
THE DEVELOPMENT OF THE HUMAN BLOOD‐BRAIN AND BLOOD‐CSF BARRIERS
Authors: MØLLGÅRD K. , SAUNDERS N. R.
Published: May 2008

The development of the human blood‐brain and blood‐CSF barriers

The commonly held belief that the fetal blood‐brain and blood‐CSF barriers are immature is reviewed. Results obtained from carefully conducted experiments with horseradish peroxidase and optimal freeze‐fracturing suggest that the chick, rat and monkey brain barrier systems to proteins are tight from the earliest stages of development. Previous studies are reviewed in the light of new information on retrograde axonal transport, circumventricular organs, the proper use of horseradish peroxidase, freeze‐fracturing, immunocytochemistry and plasma protein gene expression in the developing human brain. Original data on the development of human brain barrier systems are included. Tight junctions between cerebral endothelial and choroid plexus epithelial cells form the morphological basis for these systems. CSF in the fetus contains a remarkably high concentration of protein in contrast to adult CSF which is characterized by a very low protein concentration. This has previously been interpreted as due to immaturity of barriers in the fetal brain. Tight junctions between cerebral endothelial cells and between choroid plexus epithelial cells have been investigated in human embryos and fetuses by freeze fracture and thin section electron microscopy. As soon as the choroid plexus and the brain capillaries differentiated they exhibited well formed tight junctions. These junctions were very complex at early stages of development. A new barrier consisting of ‘strap junctions’ was found in the developing germinal matrix. The very high concentration of protein in early human fetal CSF cannot be accounted for by a lack of tight junctions
PERIPHERAL NERVE REGENERATION THROUGH GRAFTS OF LIVING AND FREEZE‐DRIED CNS TISSUE
Authors: ANDERSON P. N. , TURMAINE M.
Published: May 2008

Peripheral nerve regeneration through grafts of living and freeze‐dried CNS tissue

The ability of peripheral nerve fibres to regenerate through the central nervous system (CNS) extracellular matrix in the presence of CNS myelin debris was examined using living and freeze‐dried optic nerve grafts. The grafts were placed end‐to‐end with the proximal stumps of severed common peroneal nerves of inbred mice. Within a 4 week period, regenerating peripheral nervous system fibres were found in only two of 14 living grafts. However axons always grew into freeze‐dried grafts within one week, despite the presence of CNS myelin debris. The regenerating axons in freeze‐dried grafts were accompanied by Schwann cells and were initially found associated with the inner aspect of the glial basal lamina. Although the extracellular matrix of the freeze‐dried CNS tissue was subsequently reorganized by invading cells, it seems likely that neither the nature of the CNS extracellular matrix nor the presence of CNS myelin debris had a major inhibitory influence on peripheral nerve regeneration. It is suggested that the presence of living astrocytes covered by a basal lamina at the proximal end of the living optic nerve grafts may inhibit their penetration by regenerating axons.
EXCITOTOXIC MECHANISMS IN HYPOGLYCAEMIC HIPPOCAMPAL INJURY
Authors: SIMON R. P. , SCHMIDLEY J. W. , MELDRUM B. S. , SWAN J. H. , CHAPMAN A. G.
Published: May 2008

Light and electron microscopy were used to study the effect of hypoglycaemia on selectively vulnerable neurons of rat hippocampus with and without pharmacologic blockade of the N‐methyl‐D‐aspartate (NMDA)‐preferring receptor with 2‐amino‐7‐phosphonoheptanoic acid (AP‐7). In control hypoglycaemic hippocampi, dark cell change occurs predominantly in dentate granule cells. The topography and ultrastruc‐tural appearance of these changes is distinct from that produced by ischaemia or status epilepticus. In hypoglycaemia, mitochondrial calcium accumulation characteristic of ischaemia or status epilepticus is not seen. NMDA receptor blockade markedly attenuates the hypoglycaemic cell injury. Similar attenuation of ischaemic and epileptic brain damage by NMDA receptor blockade suggest that excessive neuronal excitation is a common mechanism of injury in each of the three conditions.
DELAYED REMYELINATION IN RAT SPINAL CORD FOLLOWING ETHIDIUM BROMIDE INJECTION
Authors: GRACA D. L. , BLAKEMORE W. F.
Published: May 2008

Areas of demyelination were produced by injecting ethidium bromide into the white matter of the lumbar spinal cord of rats. There was variation in the nature of the process of demyelination and a difference in the speed with which Schwann cells remyelinated the demyelinated axons. In some lesions, or areas within lesions, myelin debris was rapidly processed by macrophages and axons were rapidly remyelinated by Schwann cells, while in other lesions of similar duration, or in areas within the same lesion, the myelin was transformed into lattices of membranous profiles which persisted around axons for long periods of time. In the lesions containing such myelin derived membranes, there were few macrophages and remyelination by Schwann cells was delayed compared to that seen in the more rapidly resolving lesions. It was concluded that the slow resolution of some lesions resulted from the delay between intoxication and cell disintegration (7–10 days) which meant that the cell responses to demyelination took place in a glial free area which could not support cell movement needed for removal of myelin debris and remyelination. This study indicates that the tempo and results of demyelination can be altered by the cellular events which accompany degeneration of oligodendrocytes.
DO HUMAN T‐LYMPHOTROPHIC VIRUSES (HTLVs) AND OTHER ENVELOPED VIRUSES INDUCE AUTOIMMUNITY IN MULTIPLE SCLEROSIS?
Authors: DALGLEISH A. G. , FAZAKERLEY J. K. , WEBB H. E.
Published: May 2008

A virally induced autoimmune reaction may be important in the pathogenesis of multiple sclerosis. The role that glycolipids and myelin basic protein presented to the virus may play in this process is considered. The most likely cells to be the source of autoantigens are neurons, myelin and oligodendrocytes. Viral infection of class II‐expressing cells and association of the viral envelope autoantigens and the class II molecules could trigger an autoimmune reaction. It is suggested that for MS to develop following a virus infection the virus will need to cause expression of class II antigens on brain cells as well as fulfill the same role as an antigen presenting cell. The part which T‐lymphotrophic viruses (HTLVs) and other enveloped viruses may play in this phenomenon is discussed.
DYSONTOGENETIC BRAIN TUMOURS –PROPOSAL FOR AN IMPROVED CLASSIFICATION
Authors: WALTER G. F. , KLEINERT R.
Published: May 2008

The International World Health Organisation (WHO) classification of central nervous system tumours does not give an extensive classification of germ cell tumours and other malformative tumours and tumour‐like lesions. In the same way, no consistent classification of dysontogenetic brain tumours can be found in the classical handbooks. For an eventual new edition of the WHO classification, it is proposed to reconsider and improve the classification of these tumours, based on their ontogenetic relations.
MUSCLE MORPHOMETRY IN MOTOR NEURON DISEASE
Authors: FROES M. M. Q. , KRISTMUNDSDOTTIR F. , MAHON M. , CUMMING W. J. K.
Published: May 2008

It has previously been suggested that the pathological abnormalities seen in muscle biopsies from patients with motor neuron disease (MND) are of predictive value in relation to the rate of progression of the disease. In this study, quadriceps muscle biopsies from 19 patients with MND and 20 age matched controls were prepared for histochemistry and analysed morphometrically. Pathological features of denervation and reinnervation were observed in all MND patients although considerable variation between patients was noted. Motor neuron disease biopsies also showed increased connective tissue, an increased variation in fibre size, and a random fibre type distribution. Several of these abnormalities were more severe in female patients. Many of these ‘abnormalities’ were also frequent, albeit to a milder degree, in control biopsies and emphasize the need for age matched controls. The morphometric data was not related to the age of the patient, disease duration, type of MND or muscle strength, thus suggesting that the progression and severity of MND and its prognosis cannot be judged on the basis of quadriceps muscle pathology alone.
MACROPHAGE POPULATIONS ASSOCIATED WITH MULTIPLE SCLEROSIS PLAQUES
Authors: ESIRI M. M. , READING M. C.
Published: May 2008

The macrophage population within and outside plaques from eight cases of multiple sclerosis (MS) (two clinically acute, four chronic progressive and two chronic non‐progressive) has been examined in fresh frozen sections with a panel of monoclonal antibodies of macrophage, monocyte and MHC class II specificity. The majority of cells in active, hypercellular plaques, and at active borders, reacted with macrophage‐ and class II MHC‐specific antibodies, and such cells extended beyond the border between demyelinated and myelinated parenchyma. In inactive plaques such cells that reacted with macrophage‐specific antibodies were sparse and reacted only inconstantly with class II MHC‐specific antibodies. Macrophage heterogeneity was evident in as much as one macrophage antibody, RFD7, reacted only with perivascular and not parenchymal macrophages in most plaques, but reacted with a variable proportion of parenchymal macrophages in active plaques. It is suggested that the RFD7 antibody may identify a sub‐population of acute plaques, and that its use may clarify interpretation of findings related to other inflammatory cell populations by providing greater precision of classification of active plaques.