bluuebunny/crossref_metadata_2025 huggingface dataset:
‘SHAKING PUPS’: A DISORDER OF CENTRAL MYELINATION IN THE SPANIEL DOG. III. QUANTITATIVE ASPECTS OF GLIA AND MYELIN IN THE SPINAL CORD AND OPTIC NERVE
Authors: DUNCAN I. D. , GRIFFITHS I. R. , MUNZ M.
Published: May 2008

Quantification of glial cells, axonal size and myelin thickness and volume were carried out in selected areas of the three funiculi of the cervical spinal cord and the optic nerve of ‘shaking pups’ and normal littermates at 4 and 8 weeks of age. There was a marked reduction of oligodendrocytes in the affected pups with many of these cells having distended rough endoplasmic reticulum. Oligodendrocyte death was not noticeable. Astrocyte numbers were similar in both normal and affected pups. Axonal diameters were not reduced in the affected pups and there was no apparent correlation between myelination and axonal size in these animals. Total myelin volume and thickness were greatly reduced in the ‘shaking pups.’ Impaired stem cell division together with metabolic disturbance of oligodendrocytes are considered to be the main causes of the hypomyelination in this mutant.
‘SHAKING PUPS’: A DISORDER OF CENTRAL MYELINATION IN THE SPANIEL DOG. IV. FREEZE‐FRACTURE ELECTRON MICROSCOPIC STUDIES OF AXONS, OLIGODENDROCYTES AND ASTROCYTES IN THE SPINAL CORD WHITE MATTER
Authors: BRAY G. M. , DUNCAN I. D. , GRIFFITHS I. R.
Published: May 2008

Large axons identified in freeze‐fracture replicas of the spinal cord white matter of ‘shaking pups’ were encircled by spiral processes at the paranodes that appeared to arise from oligodendrocytes. In the axolemma adjacent to some of these processes there were paranode‐like intra‐membranous specializations and node‐like accumulations of E‐face particles; in other instances, no special contacts formed between axons and the spiral processes. The outer surfaces of the spiral processes, which often apposed astrocytes, frequently contained gap junctions. Although many of the abnormalities identified in this dysmyelinating mutant by freeze‐fracture electron microscopy are probably secondary to a more fundamental defect of myelin formation, the prominence of the spiral processes suggests that the encircling of axons by oligodendrocytes may be an independent state of ensheathment and not a passive effect of myelin formation.
CEREBRAL ISCHAEMIA IN THE RAT: INCREASED PERMEABILITY OF POST‐SYNAPTIC MEMBRANES TO HORSERADISH PEROXIDASE IN THE EARLY POST‐ISCHAEMIC PERIOD
Authors: DIEMER N. H. , LUBITZ D. K. J. EKSTRÖM VON
Published: May 2008

An earlier study of the rat hippocampal stratum radiatum after transient cerebral ischaemia has shown cell membrane breaks, mainly post‐synaptically, occurring as early as 20 min after an ischaemic episode. In the present study HRP was injected into the lateral ventricle 10–15 min after ischaemia and allowed to diffuse until 60 min post‐ischaemia. Ultra‐structural examination in the control animals, showed that HRP was localized exclusively in the extracellular space. After 10 min of transient ischaemia, HRP was not confined to the extracellular space, but was also seen in about 10% of apical dendrites. Only a very few pre‐synaptic terminals showed the presence of HRP. Thus, there is evidence of early post‐ischaemic membrane damage occurring in vivo in the apical dendrites of the CA‐1 pyramidal cells.
HISTOCHEMICAL AND BIOCHEMICAL STUDIES OF BUTYRYLCHOLINESTERASE ACTIVITY IN ADULT AND DEVELOPING CEREBELLUM. EFFECTS OF ABNORMAL THYROID STATE AND UNDERNUTRITION
Authors: LEGRAND Ch. , GHANDOUR M. S. , CLOS J.
Published: May 2008

The cellular and subcellular localization of BuchE activity (EC.3.1.1.8) was studied in the developing and adult rat cerebellum at light and electron microscope levels. In the adult cerebellum, BuchE activity was exclusively localized to glial cells, myelin and endothelial cells. In the immature cerebellum, BuchE activity was additionally found transiently localized to the neuroblasts of the external germinative layer and in Purkinje cells of the nodulus. In both the immature and the adult animals, the main part of the activity seemed to be membrane‐bound. The developmental pattern of cerebellar BuchE activity was assayed in developing normal, hypothyroid, thyroxine‐treated and undernourished rats. In normal newborn rats, the specific activity was higher than in adults and it showed one characteristic peak at 6 days (1–8 times the adult value reached at 30 days). At the age of 5 days, the ratio of BuchE‐containing astrocytes (numbered in the ganglionic layer) to Purkinje cells was the same as the ratio of Bergmann astrocytes to Purkinje cells determined at 35 days in Nissl preparations; their nucleus size already represented 80% of the adult value and their processes were well developed. The three experimental conditions modified the timing of BuchE development. During the early post‐natal period, it was accelerated in the thyroxine‐treated and undernourished animals, while in the hypothyroid rats it was delayed. During the same period, the number of labelled astrocytes per Purkinje cell was modified only by hypothyroidism and undernourishment. On the basis of these histochemical and biochemical results, BuchE can be considered as a good marker for the study of Bergmann glia development in the early post‐natal period.
AN ULTRASTRUCTURAL STUDY OF THE EARLY STAGES OF AXONAL REGENERATION THROUGH RAT NERVE GRAFTS
Authors: ANDERSON P. N. , MITCHELL J. , MAYOR D. , STAUBER V. V.
Published: May 2008

Segments of rat sciatic nerve 5 mm long were removed and either maintained alive in tissue culture medium or killed by freeze‐drying. Twenty‐four h later the nerve segments were replaced as autografts. Animals were killed 3–14 days after grafting. Grafts of cultured nerves (C‐grafts) always contained many living cells. Grafts of freeze‐dried nerves (FD‐grafts) contained few living cells at 3 days, but were repopulated by 7 days. A few regenerating axons were identified in the most proximal parts of 3 day C‐grafts and by 14 days many myelinated axons extended to the distal ends. Axons were absent from 3 and 7 day FD‐grafts, but by 14 days some non‐myelinated axons extended to the distal end of such grafts. Regenerating axons were always associated with Schwann cells. Small perineurial compartments were formed at the junctional zones of all grafts and throughout the FD‐grafts. Revascularization of the FD‐grafts was delayed when compared to that in C‐grafts. Fenestrated capillaries were observed in both types of graft. These experiments demonstrate that axons regenerate through FD‐grafts that have been repopulated by cells and the grafts probably lack the normal perineurial and blood/nerve diffusion barriers. The significance of these results is discussed in relation to the requirements for successful axonal regeneration.
ENDOTHELIAL GROWTH FACTOR PRODUCTION IN CULTURES OF HUMAN GLIOMA CELLS
Authors: HIRSCHBERG H.
Published: May 2008

Human glioma cells derived from biopsied material were grown in tissue culture for periods of up to 2 weeks. Supernatants from these cultures were harvested at various intervals and their ability to enhance proliferation of cultured umbilical vein human endothelial cells was assessed. All of the supernatants tested contained some degree of endothelial cell mitogenic factor activity. The activity in the supernatants reached a maximum from cultures which were 4–8 days old and gradually decreased thereafter. Supernatants from the fibroblast monolayer were not significantly stimulatory for this endothelial cell model. On the other hand, supernatants from the glioma cultures did not increase the growth of human skin fibroblast or peripheral blood lymphocytes in culture. Extracts from bovine cartilage inhibited the mitogenic activity of the supernatants from glioma cultures.
OBSERVATIONS ON THE NATURE OF SUBEPENDYMOMA: AN ELECTRON MICROSCOPIC STUDY
Authors: MOSS T. H.
Published: May 2008

Surgical biopsy material from four cases of symptomatic fourth ventricle subependymoma, all with typical light microscopic features, was studied by electron microscopy. The ultrastructural appearance of each case was similar, with small groups of tumour cell perikarya widely separated by a meshwork of cell processes containing glial filaments. Large cells lacking specialised features were prominent in all cases and showed similarities with ependymoglial precursor cells described in the adult subependymal layer of animals. Other cells showed either astrocytic or poorly developed ependymal features, and transitional forms between these two appearances were common, suggesting the tumour to be of a single cell type. Pockets of microvilli were present, but they differed from ependymal‐type micro‐rosettes in lacking tight junctional complexes. Unlike low grade astrocytomas, the extracellular space was small and there was no close association of tumour cell processes with blood vessels. These observations suggest that the subependymoma may be regarded as a separate entity from other fourth ventricle neoplasms and possibly takes origin from ependymoglial cells normally present in the adult subependymal layer.
IN VITRO METHYL MERCURY INHIBITION OF PROTEIN SYNTHESIS IN NEONATAL CEREBELLAR PERIKARYA
Authors: SARAFIAN T. A. , CHEUNG M. K. , VERITY M. A.
Published: May 2008

In an effort to characterize the principal mechanism(s) underlying the methyl mercury‐induced defect in protein synthesis in vivo and in vitro, we examined the dose and time related effects of methyl mercury chloride (MeHg) on a variety of cellular functions using bulk‐isolated neonatal cerebellar perikarya. This cell preparation demonstrated a high specific activity for protein synthesis which was optimal between 6 and 12 days of age and declined rapidly thereafter. In vitro MeHg inhibited synthesis with an ID50 of ‐ 14 μm without causing significant release of lactate dehydrogenase. The inhibition of protein synthesis occurred independently of mercurial effects on RNA synthesis, mitochondrial function, ATP content or intracellular levels of Na+ and K+. Uptake of [3H]‐phenylalanine was not appreciably affected by MeHg. The accumulated evidence suggests that in this in vitro cell model, MeHg inhibition of protein synthesis occurs via a direct interaction with the protein synthetic machinery.
ACRYLAMIDE‐INDUCED REMODELLING OF PERIKARYA IN RAT SUPERIOR CERVICAL GANGLIA
Authors: STERMAN A. B.
Published: May 2008

To extend investigations on how acrylamide affects neuronal perikarya, we studied post‐ganglionic cell bodies in the superior cervical ganglia of control and intoxicated rats (50mg/kg/day for 9–10 days) with light and electron microscopy and with stereology. By light microscopy, perikarya of intoxicated rats showed peripheral Nissl bodies and nuclear eccentricity. Ultrastructurally, many experimental neurons showed augmented Nissl bodies, often extending from nucleus to plasma membrane; cisternae of granula endoplasmic bodies often appeared in orderly stacked configurations. Intoxicated neurons had increased numbers of normal‐appearing mitochondria; some mitochondrial profiles appeared in clumps and others were hypertrophied. Compared to control neurons where Golgi complex most often aligned in a circumnuclear position, experimentals showed reductions in amount and loss of orientation. In some perikarya the pattern of eccentricity of nucleus, peripheral mantle of Nissl, and increased mitochondria gave a distinctive chromatolysis‐like appearance. Ultrastructural stereologic analysis showed significantly increased volume fractions of Nissl (P > 0.001) and mitochondria (P > 0.002), a trend towards decreased Golgi, and no change in lysosomes, confirming the ultrastructural findings. These data indicate that cell body remodelling is a widespread phenomenon, specific for different neuronal types, and that it probably acts importantly in the pathogenesis of disease.
MULTIPLE INTRASPINAL AND INTRACRANIAL EPIDERMOIDS AND LIPOMATA FOLLOWING GUNSHOT INJURY
Authors: SMITH C. M. L. , TIMPERLEY W. R.
Published: May 2008

This case report describes the presence of numerous intradural spinal and cranial epidermoids and lipomata, as an incidental finding, 14 years after a spinal gunshot injury. The aetiological factors operating in the development of such tumours are discussed with reference to the general literature and to this case.
THE ORGANIZATION OF ASTROCYTES IN ORGANOTYPIC MOUSE SPINAL CORD CULTURE: AN ELECTRON MICROSCOPE STUDY
Authors: KUSAKA H. , HIRANO A. , BORNSTEIN M. B. , RAINE C. S.
Published: May 2008

The organization of astrocytes in organotypic mouse spinal cord culture: an electron microscope study

The organization of astrocytes in myelinated culture of mouse spinal cord tissue was analysed ultrastructurally and compared with the pattern in vivo. Astrocyte cell bodies and their processes, connected by punctate adhesions and gap junctions, formed a continuous layer around the entire explant. Throughout the parenchyma, thin astrocytic processes penetrated the neuropil, separated neurons, and invested some synaptic complexes. Others formed flattened sheets and contacted directly with the basal surface of ependymal cells. In the absence of mesenchymal elements, astrocytes in vitro occasionally possessed fragments of basal lamina on the surface of the explant and around minute intercellular spaces. Except for an incomplete basal lamina, these findings indicate that astrocytes in vitro are organized in a manner essentially identical to the situation in vivo.
SOME HISTOCHEMICAL OBSERVATIONS ON INVASIVE CELLS IN A MYOPATHY INDUCED IN RATS WITH 5–HYDROXYTRYPTAMINE
Authors: CHRISTIE K. N. , MODI B. V.
Published: May 2008

Some histochemical observations on invasive cells in a myopathy induced in rats with 5‐hydroxytryptamine

The enzyme cytochemistry and proportion of mononuclear cells exclusively present within degenerating muscle fibres of the soleus of rats 24 h after a single intraperitoneal injection of 5‐hydroxytryptamine (5‐HT) (10 mg/kg) were studied. The following enzymes displayed strong cytochemical activities within these cells: non‐specific esterase (against naphthol AS‐D acetate and a‐naphthylacetate), aminopeptidase (against leucine‐4‐methoxy‐2‐naphthylamide) and dipeptidyl peptidase 11. A peroxidatic activity was also present, but was found to arise from cytochrome oxidase in phagocytosed muscle mitochondria. The aminopeptidase activity in the monocytic cells increased by roughly 50% between 6 and 24 h after 5‐HT administration. Dipeptidyl peptidase II was found, by the use of appropriate inhibitors, to be present in both mononuclear cells and muscle fibres and may be implicated in degrading the basal lamina of muscle fibres, thereby permitting access to the mononuclear cells. The morphological, enzyme histochemical and electron microscopical evidence suggest that the cells which invade muscle fibres in the early stages of a myopathy induced by 5‐HT in rats are actively phagocytosing, mature macrophages.
FELINE DYSAUTONOMIA (THE KEY‐GASKELL SYNDROME): AN ULTRA STRUCTURAL STUDY OF AUTONOMIC GANGLIA AND NERVES
Authors: GRIFFITHS I. R. , SHARP N. J. H. , McCULLOCH M. C.
Published: May 2008

Recently a feline dysautonomia of unknown aetiology, the Key‐Gaskell syndrome, has caused widespread morbidity in the UK. This report describes the ultrastructural appearances of the autonomic ganglia and axons of the sympathetic chain in this condition. Nuclei of affected neurones were eccentric and abnormally crenated. Nucleolar abnormalities such as increased electron density (due to loss of the intranucleolar vacuoles), nucleolar segregation and ring nucleoli were observed in a proportion of neurones. There was marked loss of ribosomes, both bound and unbound, and cisternae of the rough endoplasmic reticulum were distended with a floccular electron dense material. Numerous smooth‐walled cisternae were also present and complex stacks of smooth semi‐parallel membranes were observed, probably derived from the smooth endoplasmic reticulum or Golgi apparatus. No normal Golgi formations were seen. Frequent autophagic vacuoles and membranous dense bodies were present in some cells. Many unmyelinated fibres in the sympathetic chain were swollen and contained vesiculo‐tubular profiles, disordered neurotubules and filaments and various degenerating membranous organelles. Myelinated fibres within the sympathetic chain were also degenerating. These studies indicate that the organelles involved with protein biosynthesis are severely affected by the disease.
NERVE CELL LOSS IN THE PROGRESSIVE ENCEPHALOPATHY INDUCED BY ALUMINUM POWDER. A MORPHOLOGIC AND SEMIQUANTITATIVE STUDY OF THE PURKINJE CELLS
Authors: GHETTI B. , MUSICCO M. , NORTON J. , BUGIANI O.
Published: May 2008

The injection of aluminum powder into the cerebrospinal fluid induces a slowly progressing encephalomyelopathy with cerebellar atrophy. We have studied the changes in the cerebellar cortex in order to establish whether Purkinje cell loss takes place. The rabbits were killed by perfusion with paraformaldehyde and glutaraldehyde at intervals from 3 to 85 days after injection of aluminum. Changes were observed in all animals killed between 12 and 85 days after the injection. Neurofibrillary degeneration with 10 nm neurofilaments was observed in the perikaryon of Purkinje cells. The neurofibrillary tangles extended into the proximal part of the dendrites and of the axons. A time‐related deterioration of the Purkinje cells was observed. These cells appeared atrophic with eccentric and shrunken nuclei and with dark cytoplasm. By electron microscopy debris of Purkinje cell perikarya, dendrites and axons were found. The semiquantitative analysis revealed a time‐related loss of Purkinje cells. Atrophy of the molecular and granule cell layers was observed. A marked proliferation of glial cells contrasted with the severe neuronal losses. Such findings may be relevant to several human diseases in which the central nervous system is exposed to aluminum over long periods of time.
GLYCOGEN CONTENT AND FRUCTOSE‐1, 6‐BIPHOSPHATASE ACTIVITY IN METHIONINE SULFOXIMINE EPILEPTOGENIC MOUSE BRAIN AND LIVER AFTER PROTEIN SYNTHESIS INHIBITION
Authors: HEVOR T. K. , DELORME P. , GAYET J.
Published: May 2008

Glycogen content and fructose‐1, 6‐biphosphatase activity in methionine sulfoximine epileptogenic mouse brain and liver after protein synthesis inhibition

Mice given intraperitoneal injections of methionine sulfoximine (MSO) (100 mg/kg body weight) showed tonic‐clonic seizures 7 to 8h later. The protein synthesis inhibitors actinomycin D and cycloheximide, when combined with MSO delayed the onset of seizures. Methionine completely abolished the convulsions and metyrapone delayed them for some hours. Twenty‐four h after the administration of the convulsant, the activity of the gluconeogenic enzyme, fructose‐1, 6‐biphosphatase (FBPase), and the glycogen content were determined in different areas of the brain. MSO induced an increase in both FBPase activity and glycogen content. These effects were antagonized by the inhibitors of protein synthesis. Metyrapone partly inhibited MSO‐induced increases of FBPase activity and glycogen content whereas methionine completely abolished them. MSO decreased glycogen content in liver but had no effect on blood glucose level 24 h after its administration. These findings suggested that in MSO epileptogenic brain, glycogen accumulation may proceed from an enhanced gluconeogenesis.
EFFECTS OF PRENATAL EXPOSURE TO ETHANOL ON THE MATURATION OF THE PYRAMIDAL NEURONS IN THE CEREBRAL CORTEX OF THE GUINEA‐PIG: A QUANTITATIVE GOLGI STUDY
Authors: FABREGUES I. , FERRER I. , GAIRI J. M. , CAHUANA A. , GINER P.
Published: May 2008

Fabregues I., Ferrer I., Gairi J. M., Cahuana A. & Giner P. (1985) Neuropathology and Applied Neurobiology 11, 291–298

Effects of prenatal exposure to ethanol on the maturation of the pyramidal neurons in the cerebral cortex of the guinea‐pig: a quantitative golgi study

The effects of chronic ethanol consumption during gestation on the development of layer V pyramidal cells was studied quantitatively in the somatosensory cerebral cortex of the newborn guinea‐pig. The spread of the basilar dendritic arborizations and counts of dendritic spines on the apical dendrite of neurons that had been processed with the rapid Golgi method were compared with those found in age‐matched controls receiving an isocaloric diet without alcohol. There were significant differences in the number of primary basilar dendrites (P < 005) and dendritic ramifications at a distance of 25 μM from the soma (P < 0.01) between the alcohol‐exposed and control animals. There also were significant differences in the number of dendritic spines on the apical dendrite (P < 0.001). This experimental model further illustrates developmental anomalies in the cerebral cortex following prenatal ethanol exposure.
IgM PARAPROTEINAEMIA, POLYNEUROPATHY AND MYELIN‐ASSOCIATED GLYCOPROTEIN (MAG)
Authors: GREGSON N. A. , LEIBOWITZ S.
Published: May 2008

Gregson N. A. & Leibowitz S. (1985) Neuropathology and Applied Neurobiology 11, 329–347
UNCONVENTIONAL VIRUS INFECTION AND NEUROLOGICAL DISEASE
Authors: MATTHEWS W. B.
Published: May 2008

Matthews W.B. (1986) Neuropathology and Applied Neurobiology 12, 111–116

Unconventional virus infection and neurological disease
PATHOLOGY OF CREUTZFELDT‐JAKOB DISEASE ASSOCIATED WITH PITUITARY‐DERIVED HUMAN GROWTH HORMONE ADMINISTRATION
Authors: WELLER R. O. , STEART P. V. , POWELL‐JACKSON J. D.
Published: May 2008

Weller R. O., Steart P. V. & Powell‐Jackson J. D. (1986) Neuropathology and Applied Neurobiology 12, 117–129

Pathology of Creutzfeldt‐Jacob disease associated with pituitary‐derived human growth hormone administration

This report describes the pathological features in the brain of a 22 year old woman who died with Creutzfeldt‐Jakob disease 81/2 years after completing a 4 year course of injections of human growth hormone derived from cadaver pituitaries. Spongiform change was seen in the frontal cortex. There was gliosis and neuronal loss throughout the frontal cortex, basal ganglia, thalamus, peri‐aqueductal grey matter and tectum of the mid brain, pontine nuclei and dorsal medulla but no evidence of inflammation. Extensive atrophy and gliosis of the cerebellar cortex was present with widespread loss of neurons from the internal granular layer but relative sparing of Purkinje cells. Gliosis and atrophy of the mammillary bodies and gliosis of the hypothalamus may have been related to the previous surgical excision of a craniopharyngioma at the age of 21/2 years. The pattern of changes presented is comparable to that in other cases of Creutzfeldt‐Jakob disease including those previously reported after human growth hormone administration.
SCRAPIE: HOW MUCH DO WE REALLY UNDERSTAND?
Authors: KIMBERLIN R. H.
Published: May 2008

Kimberlin R. H. (1986) Neuropathology and Applied Neurobiology 12, 131–147

Scrapie: how much do we really understand?

Biological studies have produced convincing evidence for different scrapie strains, some of which undergo mutation. This argues strongly in favour of the infectious scrapie agent having a genome. The length of incubation period is influenced by the strain of agent but is also under strict host control. In mice, this control is exerted by a gene called Sine which affects the overall rate of agent replication in the CNS. After peripheral infection, invasion of the CNS from lymphoreticular sites of agent replication is a key step in pathogenesis. Evidence from one scrapie model indicates spread of infection along autonomic nerves to the thoracic spinal cord and then to other parts of the CNS. Other studies have shown that infection can spread in neurons. There are close relationships between the presence of replicating agent and the development of vacuolation, and also of cerebral amyloid when it occurs. We can, therefore, begin to understand the patterns of lesion development in the brain in terms of the targeting of infection and its replication at certain sites. Structures known as SAF (Scrapie Associated Fibrils) have been discovered in extracts of scrapie brain (but not uninfected brain) and a glycoprotein (PrP 27–30: SAF protein) is a major constituent of purified SAF. The glycoprotein is coded by a single gene which is present in several species and expressed in uninfected brain. The normal protein seems to be modified in scrapie infected brain so that it accumulates as SAF. The modified protein may also be deposited as extracellular amyloid because there appear to be common epitopes between SAF and scrapie amyloid. The biochemical nature of the scrapie agent remains in doubt and the association between infectivity and purified SAF may arise fortuitously from the fact that scrapie agent is ‘sticky’.
CEREBROVASCULAR AMYLOIDOSIS IN SCRAPIE‐AFFECTED SHEEP
Authors: GILMOUR J. S. , BRUCE M. E. , MACKELLAR A.
Published: May 2008

Gilmour J. S., Bruce M. E. & MacKellar A. (1985) Neuropathology and Applied Neurobiology 11, 173–183

Cerebrovascular Amyloidosis in scrapie‐affected sheep

Cerebrovascular amyloidosis (CA) was found in the cerebral and cerebellar cortices in 11 of 20 sheep, of six different breeds, with naturally‐occurring scrapie. The occurrence of the lesion did not appear to be influenced by the age of the sheep. This was not seen in 20 brains from age‐and breed‐matched sheep with other conditions. Furthermore, it was not found in 20 sheep experimentally infected with scrapie by sub‐cutaneous inoculation, or in 22 sheep with natural scrapie in a closed breeding group, but it was present at low frequency in a production flock, closed apart from the introduction of rams. It is concluded that this lesion is strongly associated with sheep scrapie disease, but that its occurrence varies between different groups of scrapie sheep. A major source of this variation is likely to be the strain of the agent, though other factors may be involved as has been shown for cerebral amyloidosis in experimental mouse scrapie.
RETINOPATHY IN MICE WITH EXPERIMENTAL SCRAPIE
Authors: FOSTER J. D. , FRASER H. , BRUCE M. E.
Published: May 2008

Foster J. D., Fraser H. & Bruce M. E. (1986) Neuropathology and Applied Neurobiology 12, 185–196

Retinopathy in mice with experimental scrapie

Scrapie is a naturally occurring neurological disease of adult sheep and goats with an incubation period of several years. Some strains of the causal agent can infect laboratory mice in which the incubation period, as well as the severity and distribution of vacuolar degeneration in the brain, varies according to the strain of the agent and the genotype of the mouse. Retinopathy, involving the partial or complete loss of the photoreceptor layer, was observed in a number of murine scrapie models but was absent in others. The severity of retinopathy depended on both the strain of scrapie and the genotype of mouse used. Some scrapie strains (22C, 87A and 87V) produced minimal or no retinal pathology, others (ME7, 22A and 22L) produced changes in the retinae of only certain mouse genotypes, while the strains 79A and 139A produced degeneration of the photoreceptor layer in every mouse genotype investigated. The severity of retinopathy in the various models did not correlate with the overall intensity of vacuolar degeneration in the brain, with the severity of vacuolation in the centres in the brain controlling pupillary constriction, or with the incubation period.
EVIDENCE THAT TRANSMISSIBLE MINK ENCEPHALOPATHY AGENT IS BIOLOGICALLY INACTIVE IN MICE
Authors: TAYLOR D. M. , DICKINSON A. G. , FRASER H. , MARSH R. F.
Published: May 2008

Taylor D. M., Dickinson A. G., Fraser H. & Marsh R. F. (1986) Neuropathology and Applied Neurobiology 12, 207–215

Evidence that transmissible mink encephalopathy agent is biologically inactive in mice

Transmissible mink encephalopathy (TME) is probably a form of the sheep disease, scrapie, introduced by accidentally feeding mink with scrapie‐infected sheep tissues. Although no successful transmissions of TME to mice have been achieved previous work has involved various limitations. To maximize the possibility of transmission, 176 mice, representing 14 different genotypes mostly not previously tested with TME, were injected with TME‐infected mink brain from three sources with different histories. No scrapie‐like disease was detected clinically or histologically in these mice or in a further 111 which were subsequently injected with brain or spleen material from 10 of the TME‐injected mice killed when senile. Furthermore, a series of experiments involving seven strains of scrapie, demonstrated that prior injection of mice with TME failed to affect the normal progress of scrapie infection indicating that TME agent had not occupied scrapie replication sites or otherwise influenced the pathogenesis of scrapie. The overall conclusion from these experiments is that TME is biologically inactive in mice. Although many strains of natural scrapie can be transmitted to laboratory mice, this has not been possible with all strains and it is concluded that one or more of such strains is likely to be the cause of TME in mink.
EFFECTS OF PRENATAL ETHANOL EXPOSURE ON PHYSICAL GROWTH, SENSORY REFLEX MATURATION AND BRAIN DEVELOPMENT IN THE RAT
Authors: LOPEZ‐TEJERO D. , FERRER I. , LLOBERA M. , HERRERA E.
Published: May 2008

Effects of prenatal ethanol exposure on physical growths, sensory reflex maturation and brain development in the rat

In the offspring of ethanol‐treated rats during gestation (25% ethanol in drinking water) decreased litter size, increased postnatal mortality rate, reduced body weight and body size, delayed ear opening, eyelid opening and teeth eruption, retarded air righting reflex acquisition, impaired brain growth, reduced cortical thickness and delayed maturation of layer Vth's pyramidal neurons: (a) reduced basilar dendritic arborization and (b) decreased number of spines in the apical dendrite, were observed when compared with age‐matched controls fed with a standard diet. Minimal effects were found in the offspring of fibre‐treated rats during gestation (standard diet mixed with cellulose) in which the body weight was similar to that of controls, although both the calorific intake from food and the mother's weight gain during pregnancy were similar to those of the ethanol‐treated group. All these abnormal parameters became normal at the end of the first month of postnatal life, indicating recovery of these developmental defects produced by prenatal ethanol consumption.
DEGENERATIVE CHANGES IN RAT INTRASPINAL SCHWANN CELLS FOLLOWING TELLURIUM INTOXICATION
Authors: HAMMANG J. P. , DUNCAN I. D. , GILMORE S. A.
Published: May 2008

Degenerative changes in rat intraspinal Schwann cells following tellurium intoxication

A diet containing 1.25% elemental tellurium (Te) when fed to rats in week 3 of life produces acute peripheral nervous system (PNS) demyelination. The purpose of this investigation was to determine whether Te has the same neurotoxic effect on Schwann cells and their associated myelin when located within the spinal cord. Schwann cells were induced into the CNS by irradiating the lumbosacral spinal cord of 3 day‐old rats with 4000 rads of soft X‐rays (Heard & Gilmore, 1980). At 22–28 days of age, a diet containing 1.25% Te was fed to half of these rats, and others were fed on rat chow alone. Non‐irradiated rats of the same age were divided into two similarly fed groups. At intervals from 2 to 15 days after the iniation of this diet, the rats were perfused and the irradiated portion of the cord, or comparable level in non‐irradiated rats, was trimmed and processed for light and electron microscopy and immunocytochemistry. All rats fed Te became paretic by 6–7 days, and diffuse demyelination with obvious degenerative changes in Schwann cells was seen in the nerve roots. Immunocytochemical localization of Schwann cells and peripheral myelin in the spinal cord was demonstrated using Po antiserum, and in these areas the reduction of astrocytes and their processes was shown using sections incubated with GFAP antiserum. In these areas, as in the roots, there was myelin lamellar separation, and many Schwann cells contained cytoplasmic vacuoles, hypertrophied lysosomal structures and myelin debris. Adjacent oligodendrocytes and CNS myelin were apparently unaffected, confirming a differential susceptibility of oligodendrocytes and Schwann cells. There were no Schwann cell abnormalities in the non Te‐fed irradiated rats. This experimental model provides a situation in which other neurotoxic compounds can be evaluated to compare their effects on CNS and PNS myelin in the same milieu.
STEROID HORMONE RECEPTORS IN PITUITARY ADENOMAS: A BIOCHEMICAL, IMMUNOHISTOCHEMICAL AND MORPHOMETRIC STUDY ON CRYOSTAT SECTIONS
Authors: IRONSIDE J. W. , DANGERFIELD V. J. M. , TIMPERLEY W. R. , UNDERWOOD J. C. E.
Published: May 2008

Oestrogen receptors and progesterone receptors were measured by an isoelectric focussing technique in cytosols from cryostat sections of eight human pituitary adenomas. Cryostat sections adjacent to the assayed sample were stained for anterior pituitary hormones using the peroxidase‐antiperoxidase technique, and the cellularity of each neoplasm was calculated with the aid of a computerized image analysis system. The results of ER and PR assays were adjusted to compensate for variations in cellularity. ER were present in three prolactin adenomas, one growth hormone adenoma and one gonadotrophin adenoma. The latter also contained PR. Steroid hormone receptors were not detected in two null cell adenomas and one non‐secretory oncocytoma. The results support the suggestion that antihormonal chemotherapy may be valuable in the treatment of certain pituitary adenomas.
NEURONAL ALTERATIONS IN HIPPOCAMPUS FOLLOWING SEVERE HYPOGLYCAEMIA: A LIGHT MICROSCOPIC AND ULTRASTRUCTURAL STUDY IN THE RAT
Authors: SIMON R. P. , SCHMIDLEY J. W. , SWAN J. H. , MELDRUM B. S.
Published: May 2008

Because they induce similar neuropathological changes (ischaemic cell change with microvacuolization), it has been suggested that ischaemia, status epilepticus and hypoglycaemia produce cell death by similar mechanisms, especially those resulting from intracellular calcium accumulation. We have recently demonstrated microvacuolation of neurons, mitochondrial swelling (the electron microscopic correlate of microvacuolization) and massive mitochondrial calcium sequestration (using the pyroantimonate technique) following ischaemia or status epilepticus. We therefore studied the selectively vulnerable neurons of rat hippocampus by light and electron microscopy (including the pyroantimonate technique) following 30 and 60 min of EEG isoelectricity resulting from insulin hypoglycaemia. The neuropathology at the light and EM level is unique and different from that following status epilepticus or ischaemia. The most constant finding is dark cell change of the granule cells at the tip of the dentate gyrus. In contrast to status epilepticus and ischaemia, hippocampal pyramidal neurons are far less frequently involved. Microvacuoles are rarely seen and, when present, their ultrastructural correlate is swollen Golgi apparatus, not dilated mitochondria. No intracellular calcium accumulation is demonstrable with pyroantimonate technique. Thus the cellular alterations produced by hypoglycaemia differ in character and distribution from those produced by anoxia‐ischaemia. Mitochondrial calcium accumulation is not prominent in cell death from hypoglycaemia. Whether calcium toxicity plays another, subtler role in hypoglycaemic brain injury is unknown.
RADIATION INDUCED DAMAGE IN THE CHOROID PLEXUS OF THE RAT BRAIN: A HISTOLOGICAL EVALUATION
Authors: CALVO W. , HOPEWELL J. W. , REINHOLD H. S. , YEUNG T. K.
Published: May 2008

Early and late histological changes have been investigated in the choroid plexus after the local irradiation of the brain of rats with single doses of 17‐5‐25 Gy of X‐rays. Changes were seen in epithelial cells within 1 week of irradiation. This was characterized by vacuolation, blebbing and partial lysis of the cytoplasm. Oedema in the underlying connective tissue was also seen after 1 week. A marked reduction in the number of endothelial cells, lining the walls of blood vessels, was found after 12 weeks; the severity was dose related and increased with time after irradiation. Slight atrophy of the epithelium was seen after 12 weeks.

The reduction in endothelial cell number was associated with an attempt at regeneration as indicated by endothelial nuclear enlargement, nuclear pairs or groups and by the appearance of mitotic figures. Evidence or epithelial regeneration was not seen until week 26.

Interstitial fibrosis was seen from 26 weeks after irradiation with the severity being both dose and time related. These late fibrotic changes were associated with basal membrane thickening, degenerative changes in the tunica media of arterioles and the appearance of thrombi.

These changes are compared and contrasted with those seen in other normal tissues after irradiation and are discussed in terms of their relevance to the development of late radiation damage to the central nervous system.

This work forms part of the collaborative programme of the European Late Effects Project Group (EULEP) and was partly supported by the Radiation Protection Programme of the Commission of the European Communities, Contract Nos. B10‐C‐345‐80‐D and B10‐E‐490 UKH. The Research Institute, Churchill Hospital, is supported by a grant from the Cancer Research Campaign (CRC). The authors would like to thank Miss S. Messenger for her care of the animals and Mrs B. Schur for the excellent histological preparations.
KINETICS OF THE HUMAN MEDULLOBLASTOMA CELL LINE, D283 MED, MAINTAINED IN AN ORGAN CULTURE SYSTEM. AUTORADIOGRAPHIC STUDY AFTER CUMULATIVE LABELLING IN VITRO: SIMILARITIES TO THE KINETICS OF HUMAN MEDULLOBLASTOMA IN SITU
Authors: NAKAGAWA Y. , HERMAN M. M. , BOYD J. C. , RUBINSTEIN L. J.
Published: May 2008

Cells of the human D283 Med medulloblastoma cell line were collected by gravity sedimentation and maintained in vitro in an organ culture system. The explants grew as clusters of small cells with scanty cytoplasm; some cells were arranged in solid trabeculae, sometimes forming rows and columns, and occasionally rosettes. The kinetic parameters were estimated after 6 days in vitro by cumulative labelling of the cultures with tritiated thymidine in three different experiments. The length of G2 phase (TG2) was obtained from an analysis of the fractions of continuously labelled mitoses (FCLM), the length of S phase (Ts) from the median values of grains over mitotic figures (grain index, GI), and the other parameters from mathematical models that related growth fraction (GF), TG2, total cell cycle time (Tc) and labelling index (LI) as a function of time. Mean GF, Tc, TG1, Ts and TG2 were estimated respectively to be 0.35, 30 h, 13 h, 10 h, and 7 h. These estimates correspond to those reported for human medulloblastomas in situ and confirm previous in vitro experiments which suggest that the organ culture technique is a suitable system for the study of cell kinetics in human malignant gliomas and for an analysis of the in vitro effects of chemotherapeutic agents.
EXTENSIVE EXTRAPONTINE AND CENTRAL PONTINE MYELINOLYSIS ASSOCIATED WITH CORRECTION OF PROFOUND HYPONATRAEMIA
Authors: BOON A. P. , POTTER AND A. E.
Published: May 2008

The relationship between correction of hyponatraemia and the development of central pontine myelinolysis (CPM) remains controversial. A case of CPM associated with extensive extrapontine demyelination is described. Profound hyponatraemia and its subsequent correction are documented. It is suggested that the extent of demyelination reflects the degree of hyponatraemia noted prior to correction, supporting current hypotheses regarding the role of hyponatraemia in CPM. This case is unusual in that other recognized risk factors for the development of CPM are absent.
MONOCLONAL ANTIBODY TO ALDOLASE C: A SELECTIVE MARKER FOR PURKINJE CELLS IN THE HUMAN CEREBELLUM
Authors: ROYDS J. A. , IRONSIDE J. W. , WARNAAR S. O. , TAYLOR C. B. , TIMPERLEY W. R.
Published: May 2008

A monoclonal antibody to the glycolytic enzyme aldolase C was used in an immunoperoxidase technique on unfixed and formalin‐fixed paraffin‐embedded tissues from the human central nervous system (CNS) and other tissues. No staining outside the CNS was detected. In the central nervous system the antibody gave a selective and intense staining of Purkinje cell perikarya, axons and dendrites in both fixed and unfixed tissues. In the human fetal brain, positive staining of Purkinje cells was seen from 35–36 weeks' gestation onwards. This coincides with the conversion of Purkinje cells to a tetraploid state, and may reflect increased glycolytic activity accompanying the rapid dendritic growth at this stage of development. Preliminary investigations on a variety of disease states suggest that this antibody may be useful in studies of ischaemic damage, congenital abnormalities and degenerative conditions affecting the cerebellum.
THE TOPOGRAPHIC DISTRIBUTION OF SENILE PLAQUES AND NEUROFIBRILLARY TANGLES IN THE BRAINS OF NON‐DEMENTED PERSONS OF DIFFERENT AGES
Authors: MANN D. M. A. , TUCKER C. M. , YATES P. O.
Published: May 2008

The incidence and severity of senile plaques (SP) and neurofibrillary tangles (NFT) were examined in six areas of brain in 60 non‐demented patients of age range 6–84 years. Thirty‐two patients showed neither SP nor NFT in any region (30 of these were under 65 years of age), 15 patients showed both SP and NFT in one or more regions (14 were over 60 years of age), 11 patients aged 21–84 years showed NFT only in one or more areas and two patients showed SP alone and only in the amygdala. Overall comparison of number and severity showed the greatest severity of SP within the amygdala in most instances, whereas NFT were found in most instances and at greatest severity within the hippocampus. The reason for this apparent vulnerability of these areas of brain to SP and NFT formation may lie with their connections with the outside world via the olfactory bulbs and tract. This pathway may thus provide an entry point to the brain for pathogenic agent(s) that may induce, either directly or indirectly, pathological processes that ultimately lead to SP and NFT formation.
PERIVENTRICULAR LESIONS IN MULTIPLE SCLEROSIS: THEIR PERIVENOUS ORIGIN AND RELATIONSHIP TO GRANULAR EPENDYMITIS
Authors: ADAMS C. W. M. , ABDULLA Y. H. , TORRES E. M. , POSTON R. N.
Published: May 2008

The periventricular region was studied in the brains of 129 cases of multiple sclerosis, with the purpose of establishing the mechanism and order of events in the development of the periventricular plaque, and deciding whether there is any relationship between granular ependymitis and such plaques. Periventricular plaques were found in 82‐2% of cases. Observation and computerized morphology showed that the early stage of the periventricular plaque is the formation of a lesion around a subependymal vein and that adjacent lesions later coalesce. These plaques do not appear to arise from the ependyma, which is against any role for the CSF in their initial development. Chronic or burnt‐out periventricular lesions often show overlying granular ependymitis (10‐9% of cases) and subependymal gliosis (17‐8%), presumably as a result of the long‐continued low‐grade inflammatory process. This process, which is not specific for multiple sclerosis, is sometimes associated with transfer of IgG and C3, as shown with peroxidase methods, across the subependymal vein wall and the ependymal epithelium. Increased permeability of the inflamed ependyma constitutes a possible abnormal entry route from plaque to CSF or, in reverse, from CSF to brain.
RESPONSE OF FETAL AND NEONATAL RAT BRAIN TO INJURY
Authors: MOORE I. E. , BUONTEMPO J. M. , WELLER R. O.
Published: May 2008

Previous observations have suggested that a reactive astrocytic response to damage does not occur in fetal brain. In this study the time course of the astrocytic response to injury in fetal and neonatal rat brains has been assessed using the immunoperoxidase technique for glial fibrillary acidic protein (GFAP). Cold lesions were induced in utero to the forebrain and brain stem of rat fetuses at 16–18 days of gestation. The inflammatory response and the presence of GFAP in the processes of reactive astrocytes were studied in the brains of animals killed from 4 days (20–22 days of fetal life) to 12 days (9 days of post natal life) after the injury. Reactive astrocytes containing GFAP were present at the site of injury in all fetal and neonatal rat brains. Astrocyte processes were thin and short but stained strongly for GFAP. There was a greater amount of astrocytic scar tissue in animals killed 12 days after injury than in those killed after 4 days. In contrast to adults, little mesenchymal component was observed in newly formed scar tissue on the meningeal surfaces of the fetal and newborn rat brain.
BOOK REVIEWS
Authors: WHEAL H.
Published: May 2008

Book reviewed in this article:

Gootman P. M. (Ed) Developmental Neurobiology of the Autonomic Nervous System

Riihimäki V. & Ulfvarson U. (Eds) Safety and Health Aspects of Organic Solvents
THE PROGRESSION OF THE PATHOLOGICAL CHANGES OF ALZHEIMER'S DISEASE IN FRONTAL AND TEMPORAL NEOCORTEX EXAMINED BOTH AT BIOPSY AND AT AUTOPSY
Authors: MANN D. M. A. , MARCYNIUK B. , YATES P. O. , NEARY D. , SNOWDEN J. S.
Published: May 2008

The progression of the pathological changes of Alzheimer's disease in frontal and temporal neocortex examined both at biopsy and at autopsy

Brains were obtained at autopsy from five patients with Alzheimer's disease, each of whom had undergone diagnostic craniotomy 3–7 years previously. It was possible, therefore, to examine the number (density) and nucleolar volume of pyramidal nerve cells, and the density of senile plaques and neurofibrillary tangles within the cerebral cortex on two occasions during the progression of their illness, and to assess how these measures might have changed during the period between biopsy and death. In all five patients, at biopsy, the density and the nucleolar volume of pyramidal nerve cells was significantly less than controls and, in general, values for both these measures fell significantly further from biopsy to death. By contrast, in none of the five patients did senile plaque density consistently change from biopsy to death; neurofibrillary tangle density either did not change, or indeed sometimes decreased from biopsy to death. These data show that both the clinical and the pathological progression of Alzheimer's disease is marked by a continuing loss of pyramidal cells from frontal and temporal cortex, although the densities of plaques and tangles within the cortex do not, per se, correlate with the stage of the illness. The usefulness of measurement of plaque and tangle densities as pathological criteria by which the clinical and neurochemical deficits of Alzheimer's disease can be compared in different patients is clearly questionable.
IDENTIFICATION OF THE NORMAL MICROGLIAL POPULATION IN HUMAN AND RODENT NERVOUS TISSUE USING LECTIN–HISTOCHEMISTRY
Authors: SUZUKI H. , FRANZ H. , YAMAMOTO T. , IWASAKI Y. , KONNO H.
Published: May 2008

Identification of the normal microglial population in human and rodent nervous tissue using lectin–histochemistry

Mistletoe iectin–1 (ML–1) and Ricinus communis agglutinin–120 (RCA–1) both possess D–galactose–specific surface–binding sites. They were used to selectively identify microglial populations in aldehyde–fixed normal brain tissue by lectin immunohistochemistry on paraffin and frozen sections. Mistletoe lectin–1 was superior to RCA–1 in labelling microglia in the rat brain, whereas RCA–1 labelled human microglia better than ML–1. Thus, RCA–1 and ML–1 supplement each other for identifying microglial in human and rodent central nervous system tissues. The high reproducibility of the results and the applicability of the technique to routine histology, using formalin–fixed tissue, should facilitate study of the histogenesis and role of microglia in the CNS.