bluuebunny/crossref_metadata_2025 huggingface dataset:
A CHANGE IN SUSCEPTIBILITY OF RAT CEREBELLAR PURKINJE CELLS TO DAMAGE BY ALCOHOL DURING FETAL, NEONATAL AND ADULT LIFE
Authors: PHILLIPS S. C. , CRAGG B. G.
Published: May 2008

Phillips S.C. & Cragg B.G.1982 Neuropathology and Applied Neurobiology 8, 441–454

A change in susceptibility of rat cerebellar Purkinje cells to damage by alcohol during fetal, neonatal and adult life

The sensitivity of rat cerebellar Purkinje cells to ethanol exposure during fetal, neonatal or adult life was assessed by histological techniques. Pregnant female rats were exposed to ethanol vapour during the last 2 weeks of gestation. Purkinje cells were counted 5 days after the pups were born. The number of Purkinje cells in lobe VIII was reduced by 45%, and the linear density of Purkinje cells in lobe I was 47% less than in controls not exposed to ethanol. Smaller reductions were found in other lobes. The weight of the cerebellum was reduced by 34%. Neonatal rats were exposed to ethanol vapour briefly during daylight hours on the third and fourth days after birth. Purkinje cells were counted on the fifth day after birth, and losses similar to those described above were found, with additional significant reductions of cell numbers in lobe I and of Purkinje cell density in lobe VIII. The weight of the cerebellum was reduced by only 4%. Adult male rats were exposed to ethanol vapour for 3 weeks and no Purkinje cell losses were subsequently found. The dura overlying the cerebellum of separate adult male rats was superfused with 100% ethanol for 1 h and no abnormalities were detected with electron microscopy in the exposed cortex 6 days later. It is remarkable that the brief neonatal treatment caused a more widespread loss of Purkinje cells than the 10 days of exposure to ethanol in utero, whereas the Purkinje cells present in adult animals show a great resistance to ethanol. The neonatal period seems to be a time of high susceptibility of Purkinje cells to ethanol.
CRYSTALLINE AGGREGATES OF PROTEIN‐GLYCOGEN COMPLEXES (ALIAS ‘VIRUS‐LIKE PARTICLES’) IN SKELETAL MUSCLE: REPORT OF A CASE AND REVIEW OF THE LITERATURE
Authors: PALMUCCI L. , ANZIL A. P. , LUH S.
Published: May 2008

Palmucci L., Anzil A.P. & Luh S. (1983) Neuropathology and Applied Neurobiology 9, 61–71

Crystalline aggregates of protein‐glycogen complexes (alias ‘viruslike particles’) in skeletal muscle: report of a case and review of the literature

Crystalline arrays of so‐called ‘virus‐like particles’ were found in postmortem samples of skeletal muscle obtained from an 11‐month‐old female infant. In a large number of skeletal muscle fibres crystalline inclusions were abundant, variously configurated and positively stained with a cytochemical method for polysaccharides. A battery of enzymatic tests, including some with diastase and a‐amylase, was, however, entirely non‐contributory. A muscle biopsy studied 5 months before death had disclosed no crystalline inclusions of any kind. The literature concerning similar cases of ‘virus‐like particles’, crystalline glycogen aggregates or protein‐glycogen complexes in muscle is reviewed. Possible reasons underlying the aggregation of protein‐glycogen complexes into crystalline arrays are discussed.
A QUANTITATIVE METHOD FOR COMPARING THE DISTRIBUTION OF CEREBRAL TRAUMA IN CLOSED‐HEAD INJURIES WITH AND WITHOUT TENTORIAL HERNIATION
Authors: GIBSON P. H.
Published: May 2008

Gibson P. H. (1983)Neuropathology and Applied Neurobiology9, 135–148

A quantitative method for comparing the distribution of cerebral trauma in closed‐head injuries with and without tentorial herniation

Damage to the cerebral and cerebellar hemispheres and brain‐stem was investigated in forty‐seven cases of closed‐head injury of which twenty‐four had undergone tentorial herniation. The damage was assessed by eye in coronal sections as well as microscopically using celloidin and paraffin techniques. All cases had damage to the hemispheres and brain‐stem. The types and positions of the damage were plotted on charts and quantified by using a cm2grid system. The quantity of the haemorrhage and ischaemia in the hemispheres was found by Student'st‐test to be statistically greater (P< 0001) for cases which had herniated. Haemorrhage and ischaemia were most frequently seen on the ventral aspect of the hemispheres and particularly the frontal lobes. The distribution of the haemorrhage and ischaemia was the same for both the herniated and non‐herniated brains. In a subsample of sixteen cases statistically significant differences were found using they2test for the positions of brain‐stem damageper sein herniated and non‐herniated brains. In a second subsample of thirty‐two cases a statistical difference in the position of haemorrhage was also found. The greatest damage to the brain‐stem was medial and rostral in herniated brains and paralateral and rostral but extending further caudally in non‐herniated brains. The variation in quantity of the five types of damage with length of survival was compared for herniated and non‐herniated brains.
AUTOMATED DIFFERENTIAL CELL COUNTING ON A SECTOR OF THE NORMAL HUMAN HIPPOCAMPUS: THE INFLUENCE OF AGE
Authors: MILLER A. K. H. , ALSTON R. L. , MOUNTJOY C. Q. , CORSELLIS †J. A. N.
Published: May 2008

The neurons and the glia of the human hippocampus are notoriously vulnerable in various pathological conditions including those linked to ageing. There may even be differences between the young and the old in the absence of manifest disease. Using an image analyser, systematic measurements of cell numbers in the region of the Sommer (Hl) sector of the human hippocampus have been made on post‐mortem tissue from thirty‐seven female and forty‐nine male subjects aged between 15 and 96 years. In fifteen male and fifteen female subjects both hemispheres were available for analysis so that measurements were made on a total of 116 hemispheres. For each specimen the fresh volume of the hemisphere was measured and corrections subsequently made for changes in size which occurred during fixation, processing, mounting and staining. After all the correction factors had been applied the number of nucleolated neurons was found to fall by about 3.6% per decade (P<0.0001). There was no significant age‐related change in the number of glia. Marked individual variations were found.
THE EFFECT OF AGE ON BIOCHEMICAL AND MORPHOLOGICAL CHANGES IN THE SEMITENDINOSUS MUSCLE OF CATTLE WITH GENERALIZED GLYCOGENOSIS TYPE II
Authors: HOWELL J. McC. , DORLING P. R. , COOK R. D.
Published: May 2008

Progressive changes in acid alpha‐glucosidase activity, glycogen content and light microscopical and ultrastructural features in skeletal muscle of calves affected by generalized glycogenosis type II were assessed in biopsies from semitendinosus muscle of nine affected, twenty‐six carrier and fifteen normal calves taken at varying times between birth and 17 months of age. Affected animals could be identified by using the PAS technique on paraffin and epon embedded material or by electron microscopy. However, estimation of acid alpha‐glucosidase activity was required for precise diagnosis of generalized glycogenosis type II or to distinguish between normal and carrier animals. The glycogen content of the semitendinosus muscle of affected animals was approximately three times that in non‐affected animals and although storage of glycogen reached a plateau soon after birth, the muscle fibre damage seen in very young calves increased with age. Morphological evidence of glycogen accumulation, both within the cytoplasm and within membrane bound structures, was present at birth. In some animals evidence of muscle fibre regeneration and damage was seen in the same sections.
VIMENTIN INTERMEDIATE FILAMENTS IN CULTURES OF HUMAN MENINGIOMAS
Authors: LOLAIT S. J. , UNDERWOOD J. R. , MU F‐T. , ALDERUCCIO F. , DOW C. A. , PEDERSEN J. S. , CHALMERS P. J. , TOH B. H.
Published: May 2008

Monolayer cultures of six human meningiomas and meningeal cells from a human foetus were examined by indirect immunofluorescence with a human autoantibody to intermediate filaments and with a monoclonal antibody to vimentin intermediate filaments. No difference could be demonstrated in the staining of an intricate fibrillar network in cultures of transitional, fibroblastic, psammomatous and sarcomatous meningiomas compared to those of human foetal meninges. Many meningotheliomatous meningioma cells showed staining of distinctive ‘whorls’ of intermediate filaments, an observation less frequently seen in fetal meningeal cells or in meningiomas of other histological types. Meningioma cells, pretreated with vinblastine, showed staining of rearranged filaments whose conformation and compactness varied from cell to cell. A striking observation frequently seen in transitional and psammomatous meningiomas was the staining of thick intermediate filament ‘bands’ bridging two contiguous meningioma cells. Immunoblotting experiments confirmed the presence of vimentin intermediate filaments in the cultured meningioma cells.
MORPHOMETRIC APPROACHES TO PERIFASCICULAR ATROPHY IN MUSCLE BIOPSY: DO THEY HELP TO DIAGNOSE POLYMYOSITIS?
Authors: PALJÄRVI L. , SNÄLL E‐V.
Published: May 2008

The sizes of muscle fibres in the peripheral and central parts of fascicles were compared in biopsies from patients with polymyositis/ dermatomyositis, patients with slowly progressing muscular dystrophies and normal controls. Of three quantitative parameters tested, perifascicular atrophy factor gave the best discrimination between the patient groups. This factor is obtained by subtracting the atrophy factor of the peripheral fibres from that of the central ones. In polymyositis, the values tend to be negative as a result of atrophy affecting selectively the peripheral fibres, whereas in dystrophies the values are usually close to zero or positive. For the comparison between polymyositis and muscular dystrophy, the test based on perifascicular atrophy factor has an estimated sensitivity of 83% and a specificity of 65%. This quantitative method is thus able to increase sensitivity of the diagnosis of polymyositis over that attained by the subjective evaluation, even at the cost of a sizeable false‐positive rate.
LYMPHOMATOID GRANULOMATOSIS WITH CEREBRAL INVOLVEMENT
Authors: IRONSIDE J. W. , MARTIN J. F. , RICHMOD J. , TIMPERLEY W. R.
Published: May 2008

We report the case of a 26–year‐old man who suffered from lymphomatoid granulomatosis. The light microscopical features of a biopsy from involved cerebral tissue are described and for the first time the cytological findings on a brain smear are illustrated. The results of immunological and electronmicroscopical investigations are consistent with the suggestion that this disease may be a disorder of T lymphocytes. It is suggested that the smear technique may be used to confirm the presence of cerebral disease in patients with an established diagnosis, and to investigate suspected patients who present with extrapulmonary manifestations.
ADRENOLEUKODYSTROPHY: CLINICAL, PATHOLOGICAL AND BIOCHEMICAL FINDINGS IN TWO BROTHERS WITH THE ONSET OF CEREBRAL DISEASE IN ADULT LIFE
Authors: ESIRI M. M. , HYMAN M. , HORTON L. , LINDENBAUM R. H.
Published: May 2008

Adrenoleukodystrophy: clinical, pathological and biochemical findings in two brothers with the onset of cerebral disease in adult life

Two brothers are described in whom adrenoleukodystrophy (ALD) presented as progressive cerebral degeneration in early adult life. Diagnosis during the life of one brother was based on cerebral biopsy appearances. At autopsy there was a leucodystrophy and an additional myelopathy in both cases. Biochemical studies carried out on the propositi and other family members revealed characteristic abnormalities of ALD in the propositi and two, as yet clinically unaffected, adult brothers, and abnormalities characteristic of the heterozygous state in their mother. Neither of the clinically affected brothers showed clinical features of hypoadrenalism and these cases emphasize the importance of considering the diagnosis of ALD in adult males with leucodystrophy even in the absence of overt adrenal insufficiency.
INFANTILE HYPOTHALAMIC HAMARTOMA WITH MULTIPLE CONGENITAL ABNORMALITIES
Authors: NURBHAI M. A. , TOMLINSON B. E. , LORIGAN‐FORSYTHE B.
Published: May 2008

This case report describes a hypothalamic hamartoma with multiple congenital abnormalities in a male infant, with a post‐mortem examination and histology of the lesion.
GLYCOGEN PARTICLES IN METHIONINE SULFOXIMINE EPILEPTOGENIC RODENT BRAIN AND LIVER AFTER THE ADMINISTRATION OF METHIONINE AND ACTINOMYCIN D
Authors: DELORME P. , HEVOR T. K.
Published: May 2008

Glycogen particles in methionine sulfoximine epileptogenic rodent brain and liver after the administration of methionine and actinomycin D

Rats and mice were submitted either to the convulsant methionine sulfoximine (MSO) alone or to MSO combined with actinomycin D or methionine respectively. Twenty‐four hours after the intraperitoneal administration of these compounds, the animals were killed and tissue samples were prepared for electron microscopy. Methionine sulfoximine induced ‘grand mal’ type seizures which were abolished by methionine. In saline controls, glycogen was as β particles located in the cytoplasm of astrocytes, i.e. in perikarya and processes. Liver glycogen was as perinuclear masses of a and β particles or as αparticles scattered in all the cytoplasm. When the rodents were treated with MSO, glycogen was as α and β particles which invaded all areas of the astrocyte cytoplasm, this increase being tremendous in perivascular end feet. Actinomycin D slowed down the accumulation of glycogen particles while methionine completely abolished it. In any case, glycogen particles were confined to the astrocytes and were never seen in other types of cells. In liver, MSO induced an important decrease or a complete disappearance of glycogen particles. When the convulsant was combined with actinomycin D or with methionine, the figures looked like those of controls. These results have been discussed in relation to the mechanism of glycogenesis in central nervous system of rodents submitted to MSO.
AGE‐RELATED VARIATIONS IN THE NEURON CONTENT OF THE CEREBRAL CORTEX IN SENILE DEMENTIA OF ALZHEIMER TYPE
Authors: HUBBARD B. M. , ANDERSON J. M.
Published: May 2008

Hubbard B. M. & Anderson J. M. (1985) Neuropathology and Applied Neurobiology, 11, 369–382

Age‐related variations in the neuron content of the cerebral cortex in senile dementia of Alzheimer type

The cell content of the cerebral cortex in senile dementia of Alzheimer type has been examined using a stereological method which combines gross cortical measurements and microscopical observations to give volumetric data on cells and neuropil. In the neocortex only the large (> 12 µm diameter) neuron fraction was found to be abnormal; the volume of these cells was reduced in most patients aged less than 80 years, but was not usually abnormal for age in older cases. Smaller neurons and glial cells showed no consistent change from normal values. Neuropil was diminished in both age groups, so that patients over 80 years of age tended to show cerebral atrophy without neocortical neuron loss. By contrast to the neocortex, the subiculum of the hippocampus consistently showed pathological neuron loss in both age groups.
A MORPHOMETRIC STUDY OF THE MICROVASCULATURE OF A RAT GLIOMA
Authors: LUTHERT P. J. , LANTOS P. L.
Published: May 2008

Luthert P. J. & Lantos P. L. (1985) Neuropathology and Applied Neurobiology, 11, 461–473

A morphometric study of the microvasculature of a rat glioma

Intracerebral tumours were produced in BD IX rats by the inoculation of neoplastic astrocytes. Following perfusion‐fixation, 10 firw sections were stained with toluidine‐blue and photographed so as to construct photomontages embracing deep tumour, tumour edge and surrounding brain. Thirteen montages from 9 tumours were studied. Successive 200 mm samples were analysed with a digitizing tablet and, for each sample the following were measured (a) the number of vascular profiles per unit area, (b) the mean vessel circumference and diameter and (c) the approximate fractions of the sample occupied by tumour and necrosis. Towards the tumour centre, vascular density dropped to 20% of that for normal cortex but vessel size more than doubled. The surface area fraction of the vessels reached a maximum at the tumour edge.

These results provide not only an anatomical framework for both a variety of physiological studies and for the investigation of angiogenesis in this system but also have pharmacokinetic implications for the treatment of brain tumours.
CREUTZFELDT‐JAKOB DISEASE: IMPLICATIONS FOR GROWTH HORMONE DEFICIENT CHILDREN
Authors: PREECE M.A.
Published: May 2008

For over 25 years children with short stature due to growth hormone deficiency have been able to achieve normal height with the aid of human growth hormone (hGH) injections. Following reports of four deaths due to Creutzfeldt‐Jakob disease (CJD) in young adults previously treated with hGH this treatment has ceased. There are major implications due to the potential risks of further cases of CJD and to the lack of a previously well‐tried therapeutic substitute.
CALCIFICATION IN THE HUMAN CHOROID PLEXUS, MENINGIOMAS AND PINEAL GLAND
Authors: ALCOLADO J. C. , MOORE I. E. , WELLER R. O.
Published: May 2008

Calcification in the human choroid plexus, meningiomas and pineal gland

Calcification in the stroma of adult telencephalic choroid plexus was studied of 20 postmortem brains and one biopsy by light microscopy, transmission and scanning electron microscopy and compared with calcification in psammoma bodies in normal arachnoid, five spinal meningiomas and in calcospherites of six pineal glands. Fifteen fetal and newborn choroid plexuses were also examined by light microscopy. Calcium deposition was observed in the subepithelial regions of the adult choroid plexus, in the walls of blood vessels but was mostly seen in spherical psammona bodies. Collagen whorls 20–60 μm in diameter and surrounded by arachnoid cells, were observed in the stroma of the choroid plexus; calcium, phosphorous and iron were deposited in the collagen whorls to form psammoma bodies. Matrix vesicles and spicules resembling hydroxyapatite were associated with the arachnoid cells surrounding the collagen whorls and with the collagen fibres within the whorls. The dense amorphous calcified core of each psammoma body was surrounded by an outer coating of entwined collagen fibres readily visible by scanning electron microscopy. Similar psammoma bodies were occasionally observed in normal arachnoid. Psammoma bodies in meningiomas resembled those in the choroid plexus stroma. Calcospherites in the pineal differed from psammoma bodies; they were lobulated, more irregular in shape and did not have a collagen base. The results of this study suggest that psammoma bodies in the choroid plexus, as in meningiomas, form by a process of dystrophic calcification associated with arachnoid cells and collagen fibres. The presence of iron in the choroid plexus psammoma bodies may be a result of haemorrhage into the stroma. The mechanism of calcification in pineal remains unclear.
RACTERISTICS OF HUMAN MEDULLOBLASTOMA CELL LINE TE‐671 UNDER DIFFERENT GROWTH CONDITIONS IN VITRO: A MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY
Authors: MØRK S. J. , MAY E. E. , PAPASOZOMENOS S. CH. , VINORES S. A.
Published: May 2008

Characteristics of human medulloblastoma cell line TE‐671 under different growth conditions in vitro: a morphological and immunohistochemical study

The human medulloblastoma cell line, TE‐671, was studied in vitro both in monolayer culture and in a three‐dimensional culture system using gelfoam as the supporting matrix. Flow cytometry studies of cells grown in monolayer culture revealed a unimodal, tetraploid DNA content. Most cells in both in vitro systems contained neuron‐specific enolase (NSE), actin, and tubulin, while only occasional cells or cell clusters contained the 68 000 molecular weight subunit of neurofilaments (NF mol. wt 68 000) or microtubule‐associated protein 2 (MAP‐2). In monolayer culture, long cellular processes containing NSE, NF mol. wt 68 000 and MAP‐2, which were present at 2 days, were nearly absent by 7 days. All antigens were present at 4 days in the organ culture system; by 72 days, cells still stained positively for NF mol. wt 68000 and MAP‐2, but staining for NSE, actin, and β‐tubulin was diminished as compared to 4 days. Retinoic acid (RA) in the 13‐cis isomer form at 10‐6 M was applied to monolayer cultures at day 1 for 6 days and to gelfoam cultures at day 1 for 28 days. RA did not significantly alter cell proliferation up to 7 days in vitro and did not appreciably affect cellular expression of NSE, NF mol. wt 68000, MAP‐2, β‐tubulin, or actin in either system. By electron microscopy, most cells grown under different culture conditions with or without RA treatment appeared to be undifferentiated and polygonal, with occasional cytoplasmic annulate lamellae.

The immunohistochemical and ultrastructural features reported indicate that the TE‐671 medulloblastoma line is composed primarily of primitive neuroepithelial cells with a limited potential for neuronal differentiation. This differentiation was not promoted by RA or by an in vitro system known to favour differentiation in a number of human and animal nervous system tumours. The findings suggest that the cells of the TE‐671 line lack either receptors for retinoic acid or the capacity to respond to bound retinoic acid.
A QUANTITATIVE STUDY OF THE ULTRASTRUCTURE OF PYRAMIDAL NEURONS OF THE CEREBRAL CORTEX IN ALZHEIMER'S DISEASE IN RELATIONSHIP TO THE DEGREE OF DEMENTIA
Authors: SUMPTER P. Q. , MANN D. M. A. , DAVIES C. A. , NEARY D. , SNOWDEN J. S. , YATES P. O.
Published: May 2008

A quantitative study of the ultrastructure of pyramidal neurons of the cerebral cortex in Alzheimer's disease in relationship to the degree of dementia

Quantitative morphometric (stereological) methods have been used to measure the number or amount of organelles in pyramidal nerve cells, unaffected by neurofibrillary degeneration, in biopsy specimens of temporal cortex from 11 patients with Alzheimer's disease, and to relate these to the degree of dementia, as measured by psychometric testing. Only areal proportion (AA) and surface area (SA) of rough endoplasmic reticulum were significantly reduced in line with the severity of the degree of dementia. It is suggested that these changes reflect a progressively diminishing requirement for packaging and transport of replacement proteins, particularly in relation to neurotransmitter metabolism in nerve terminals following the loss of synapses which we have shown to occur in these patients.
CYTOFLUOROMETRIC QUANTIFICATION OF SOMATOPETAL AXONAL TRANSPORT: EFFECTS OF A CONDITIONING LESION AND 2,5‐HEXANEDIONE
Authors: NENNESMO INGER , KRISTENSSON KRISTER
Published: May 2008

Cytofluorometric quantification of somatopetal axonal transport: effects of a conditioning lesion and 2,5‐hexanedione

Cytofluorometric quantification of axonally transported fluorescein isothiocyanate (FITC)‐labelled wheat germ agglutinin (WGA) from the injection site in the snout area was performed in the facial nucleus at various times during regeneration of one of the facial nerves. Measurements were made on single neurons on both operated and non‐operated sides in three different groups of mice 8, 12 and 16 days after a nerve crush, Group 1: (control group) animals with a nerve crush, Group 2: animals with a conditioning lesion (nerve injury) made 3 days before the nerve crush, and Group 3: animals exposed daily to 2,5‐hexanedione from 2 weeks before nerve crush until killing. A conditioning lesion caused a more rapid return of transport in regenerating nerves but there was no evidence for an increase in the total amount of transported FITC‐WGA. For mice exposed to 2,5‐hexanedione a transient increase of tracer transport in regenerating nerves could be demonstrated on day 12 after nerve crush. On day 16, however, a reduction of transport was seen in both operated and non‐operated nerves. This study shows that it is possible experimentally to manipulate the influx of macromolecules to the nerve cell body from the periphery during nerve regeneration, and the present method offers the opportunity to study quantitatively the effects of various treatments on reinnervation of a muscle.
VASCULAR PERMEABILITY IN TRANSPLANTABLE MURINE GLIOMAS: MORPHOLOGICAL CORRELATION WITH TRACER STUDIES
Authors: PIRES M. M. , PILKINGTON G. J. , LANTOS P. L.
Published: May 2008

Invasive astrocytomas were produced in mice by intracerebral injection of a cell line obtained from a spontaneous murine astrocytoma. These tumours grew in the cerebral hemispheres and, in many cases, extended through the needle hole in the skull to give rise to large extracranial tumours. On injection of the tracers, Evans' blue or horseradish peroxidase (HRP), into the femoral vein, differences were noted in the vascular permeability of the intracerebral and extracranial tumours; the latter alone being stained. Ultrastructurally, small amounts of HRP were localized on the luminal membranes of the vascular endothelium in intracerebral tumours, while in extracranial neoplasms, the tracer was present in the widened extracellular space and in the cytoplasm of macrophages and neoplastic cells. Accordingly, endothelial fenestrations, open junctions and irregular vessels with hypertrophic endothelia were seen exclusively in extracranial neoplasms. These anomalies in the vasculature of intracerebral and extracranial components of VMDk P 497 tumours may have important implications in chemotherapeutic studies using this glioma model.
STUDIES ON THE NEUROBIOLOGY OF VITAMIN E (ALPHA‐TOCOPHEROL) AND SOME OTHER ANTIOXIDANT SYSTEMS IN THE RAT
Authors: GOSS‐SAMPSON M. A. , MULLER D. P. R.
Published: May 2008

To understand why nervous tissue should be particularly affected by severe deficiency of vitamin E, the distribution of vitamin E (alpha‐tocopherol) and some other antioxidant systems was investigated. The concentration of vitamin E and the activities of glutathione peroxidase and superoxide dismutase were determined in different regions of the nervous system in male Wistar rats. The cerebral cortex had the highest, and the cerebellum the lowest concentration of alpha‐tocopherol (P< 0.02). Activity of glutathione peroxidase tended to show an inverse relationship to the alpha‐tocopherol concentration, whereas superoxide dismutase activity was evenly distributed through the nervous tissue. Vitamin E concentrations were also determined in spinal cord, sciatic and tibial nerves and in epineurial, myelin and non‐myelin fractions of the sciatic nerve. Uptake of intravenously injected tritiated alpha‐tocopherol was studied after 6 h and found to be greater in brain and peripheral nerve than cervical and thoracic regions of the spinal cord. Uptake of tocopherol varied along the sciatic and tibial nerve, being greatest where the sciatic nerve divided into tibial, sural and common peroneal nerves. This corresponded to an area of increased vasculature which was visualized by an angiographic technique using barium sulphate.
NEURONOTOXICITY OF AXONALLY TRANSPORTED TOXIC LECTINS, ABRIN, MODECCIN AND VOLKENSIN IN RAT PERIPHERAL NERVOUS SYSTEM
Authors: WILEY R. G. , STIRPE F.
Published: May 2008

In an attempt to find new and more useful suicide transport agents, the cytotoxic lectins abrin, modeccin and volkensin were pressure microinjected into peripheral nerves (vagus, hypoglossal and sciatic) of adult rats. After 33 h‐5 days survival, the brainstems, spinal cords and corresponding sensory ganglia were examined histologically. All three lectins produced profound chromatolysis, and destruction of sensory and motor neurons projecting axons through the injected nerves. Volkensin and modeccin were significantly more potent than any previously reported suicide transport agent. It is concluded that abrin, modeccin and volkensin are effective, unselective suicide transport agents in the rat peripheral nervous system but none is clearly superior to ricin for making restricted sensory and motor neuron ablations. However, modeccin and volkensin are fundamentally different from any previously reported suicide transport agents with respect to spread within the CNS which destroyed neurons adjacent to those initially taking up and transporting the toxin. Possibly this is due to the different oligosaccharide binding specificity of modeccin and volkensin compared to other suicide transport agents. Modeccin and/or volkensin may prove useful in making lesions of CNS interneurons using the suicide transport strategy.
THE PATHOLOGICAL EFFECT ON THE CENTRAL NERVOUS SYSTEM OF MICE FOLLOWING SINGLE AND REPEATED INFECTIONS OF THE DEMYELINATING A7(74) STRAIN OF SEMLIKI FOREST VIRUS
Authors: ILLAVIA S. J. , WEBB H. E.
Published: May 2008

The pathological effect on the central nervous system of mice following single and repeated infections of the demyelinating A7(74) strain of Semliki Forest virus

The avirulent strain A7(74) of Semliki Forest virus was inoculated intraperitoneally into mice at weekly intervals for 7 weeks. Pathological, virological and serological studies were carried out twice weekly, after each infecting dose. Similar studies were performed on mice that had been given repeated inoculations at 2, 3 or 4 weekly intervals as were a group of control mice given a single dose of SFV.

Results showed grossly enhanced central nervous system lesions, in particular the perivascular cuffing and demyelination, after the 2nd and 3rd weekly inoculation. With further injections there was no increase in severity of the lesions and by the eighth inoculation the pathological changes in the brain appeared to have recovered. The maximum and most persistent damage to the brain was seen after the 2nd and 3rd weekly inoculations. As the interval between two SFV inoculations was increased, the lesions in the central nervous system were reduced and protection increased. Virus in the blood was only detectable after the first inoculation and brain virus after the first and second inoculations. Peak IgG antibody levels were seen on day 46 after a single inoculation and day 35 in the multiple inoculations.

It was concluded that repeated inoculations of SFV do not produce a relapsing demyelinating disease, but the 7th and 14th day inoculations do enhance the lesions which are seen to persist after the inoculation on the 21st day. In spite of the gross pathological changes inflicted, the brain damage appears to recover.
THE EFFECTS OF THIOCTIC ACID ON MOTOR NERVE TERMINALS IN ACRYLAMIDE–POISONED RATS
Authors: KEMPLAY S. , MARTIN P. , WILSON S.
Published: May 2008

The effects of thioctic acid on motor nerve terminals in acrylamide–poisoned rats

Acrylamide causes a distal neuropathy by combining with and depleting glutathione and other sulphydryl–containing compounds in axons and nerve terminals. This results in damage to the axon membrane and impaired efficiency of synaptic vesicle recycling. The changes may be assessed by staining nerve terminals in muscle with zinc iodide and osmium, a technique which depends upon the presence of sulphydryl compounds for the development of the stain. The present experiments were designed to test whether thioctic acid, itself a sulphydryl–containing compound, could protect against acrylamide–induced damage of motor nerve terminals. In vitro and in vivo experiments on acrylamide–poisoned rats showed that thioctic acid was able to maintain the integrity of the nerve terminal membrane, as shown by the ability of the terminals to develop ‘spontaneous’ sprouts and to stain with the zinc iodide osmium technique. Thioctic acid treatment also enhanced recovery after partial denervation of muscles in both normal and acrylamide–poisoned animals. The results suggest that thioctic acid is itself able to react with the acrylamide before the latter has a chance to bind and deplete axonal and nerve terminal glutathione.
THE EFFECTS OF ALUMINIUM ON BRAIN GANGLIOSIDES IN URAEMIC RATS TREATED WITH 24R, 25–DIHYDROXYVITAMIN D3
Authors: VUKIčEVIć S. , KRAčUN I. , STAVLJENIć A. , KELOVIć Z. , KREMPIEN B. , RÖSNER H.
Published: May 2008

The effects of aluminium on brain gangliosides in uraemic rats treated with 24R, 25‐dihydroxyvitamin D3

The administration of aluminium to uraemic rats leads to aluminium accumulation in different brain regions. Aluminium intoxication significantly alters brain gangliosides, the content of which is increased in uraemic animals. This phenomenon can be prevented by administration of 24R, 25‐dihydroxyvitamin D3 (24, 25(OH)2D3).

Our results could possibly find an application in the prevention of aluminium‐induced encephalopathy in patients on haemodialysis.
AN ANALYSIS OF THE MORPHOLOGY OF SENILE PLAQUES IN DOWN'S SYNDROME PATIENTS OF DIFFERENT AGES USING IMMUNOCYTOCHEMICAL AND LECTIN HISTOCHEMICAL TECHNIQUES
Authors: MANN D. M. A. , BROWN A. , PRINJA D. , DAVIES C. A. , LANDON M. , MASTERS C. L. , BEYREUTHER K.
Published: May 2008

The morphology of the senile plaque (SP), within the hippocampus and the temporal cortex, has been examined in 21 patients with Down's syndrome (DS), dying between the ages of 13 and 65 years, using immunocytochemical and lectin histochemical methods, as well as with a conventional silver staining technique. The earliest changes detectable within these areas of brain in the younger patients involved a fine diffuse deposition of amyloid (A4) protein and a uniform granular accumulation of an oligosaccharide recognized by the lectin from Canavalia ensiformis (ConA). At this stage, these ‘pre—plaque’ areas are unrecognizable using silver staining. Later the conventional SP morphology becomes apparent; the A4 protein aggregates into the usual plaque core and neurites appear with silver staining. The fine ConA positive material concentrates into large clumps and becomes recognizable by other lectins such as PSA, WGA and ePHA, which bind to mannose containing structures in an increasingly complex form. It is suggested that the development of the pathological changes of Alzheimer's disease, in patients with DS (and also in AD itself) involves a primary deposition of amyloid protein in conjunction with the accumulation of an as yet unidentified oligosaccharide. These changes precede the neuronal response that is characterized by the formation of neurites and the accumulation of neurofibrillary tangles that ultimately leads to cell death.
REVERSIBLE NEURONAL DAMAGE IN HIPPOCAMPAL PYRAMIDAL CELLS WITH TRIETHYLLEAD: THE ROLE OF ASTROCYTES
Authors: NOLAN C. C. , BROWN A. W.
Published: May 2008

A single dose (19 mgkg‐1) of triethyllead given to weanling rats produces necrosis in a small number of hippocampal pyramidal (CA3) and hilar neurons with reversible changes in the remaining neurons of this region. The sequence of events has been studied by light and electron microscopy over a period from 12 h to 14 days after dosing. Early changes resemble those previously described for trimethyltin, with the formation of characteristic tubulo–vesicular dense bodies by 12 h accompanied by vacuolation of Golgi and smooth surfaced endoplasmic reticulum (SER) elements which became generalized by 24 h. Large numbers of secondary dense bodies, formed from tubulo–vesicular dense bodies as well as from autophagosomes, were present by 48 h, whilst very little rough surfaced endoplasmic reticulum (RER) and few polyribosomes remained and vacuolation was much reduced. In those animals which did not die from seizures, the majority of hippocampal pyramidal cells were able to recover from these changes with astrocytes playing a significant role in the elimination of the dense bodies. This involved astrocytes inserting processes into the neuronal perikaryon from where the secondary dense bodies were selectively transferred into the astrocyte cytoplasm. This activity was first seen at 48 h, reached a peak at 4 days, when most CA3 neurons contained one or more astroglial intrusions and subsided soon after. The surviving neurons returned to apparent normality over the period from 3 to 7 days with a gradual return of polyribosomes, Golgi elements and RER.
Non‐missile head injury: report of a patient surviving for 6 years
Authors: MIZUTANI Y. , HAYAKAWAt K. , TAKIZAWA T. , MATSUMOTO M. , MORIMATSU Y.
Published: May 2008

A female patient with non‐missile head injury is described. She showed slight improvement in her level of consciousness, and survived for 61/2 years after injury. At autopsy, the white matter lesions were localized rather than diffuse in distribution. In addition to lesions in the corpus callosum, anterior commissure and dorsolateral quadrant of the rostral brain stem, those in the parasagittal cerebral white matter, and in the hilus of the dentate nucleus and superior cerebellar peduncle were considered to be due to primary axonal injury. A cavity in the frontal white matter was remarkable in that there was no evidence to indicate expansion of the lesion due to haemorrhage. These features suggested that the injurious physical forces had acted parallel to the direction of the axons.
Granulomatous angiitis and cerebral amyloid angiopathy presenting as a mass lesion*
Authors: LE COZ P. , MIKOL J. , FERRAND J. , WOIMANT F. , MASTERS C. , BEYREUTHER K. , HAGUENAU M. , COPHIGNON J. , PEPIN B.
Published: May 2008

A woman, who presented with clinical and radiological signs of a right temporal mass suggestive of a brain tumour, was found to have granulomatous angiitis associated with cerebral amyloid angiopathy; the diagnosis was confirmed by biopsy. She is still well 13 years after excision of the lesion. The association of granulomatous angiitis and cerebral amyloid angiopathy constitutes a peculiar variety of central nervous system micro‐angiopathy. Only a few similar cases have been described.
Loss of axonal contact causes down‐regulation of the PLP gene in oligodendrocytes: evidence from partial lesions of the optic nerve
Authors: McPHILEMY K. , GRIFFITHS I. R. , MITCHELL L. S. , KENNEDY P. G. E.
Published: May 2008

We have examined the influence that axons may have on the expression of proteolipid protein (PLP), the major myelin protein of the CNS. Partial transections were made of the optic nerve of adult rats to produce approximately a 50% loss of axons. Twenty‐eight days after lesioning, sections of the distal nerves were immunostained for GFAP and neurofilament protein and hybridized for PLP mRNA. The area of astrocytosis, as defined by GFAP immunostaining, usually exceeded the extent of axonal loss. PLP mRNA expression in oligodendrocytes in the denervated area of the lesioned nerve was reduced compared to the innervated zones of the lesioned nerve and the contralateral intact nerve. This down‐regulation correlated with the axonal loss rather than the area of astrocytosis. The data support the contention that axons are necessary for oligodendrocytes to maintain full expression of their major myelin protein genes.
Barrier functions of the leptomeninges: a study of normal meninges and meningiomas in tissue culture
Authors: FEURER D. J. , WELLER R. O.
Published: May 2008

The anatomical arrangement of the pia mater suggests that it may act as a regulatory interface between cerebrospinal fluid and the surface of the brain and between arterioles within the brain and the surrounding neural tissue. However, the functional aspects of such a barrier are difficult to evaluate in vivo. In the present study, the enzymic content and endocytotic capacities of normal leptomeningeal cells in situ and meningioma cells in confluent tissue culture are examined in relation to barrier functions of meningeal cells. Growth of cells in culture was obtained from human fetal and newborn rat leptomeninges and from 9/13 meningiomas. But, in only two meningiomas were the cultured cells characterized as meningeal in origin by using the strict criteria of desmosomes identified by immunocytochemistry or by electron microscopy. These two tumours had high (8–8.7%) Ki‐67 labelling indices. Glutamine synthetase activity is present in normal meninges and in meningioma cells in culture; this enzyme together with catechol‐O‐methyltransferase could play a role in limiting the diffusion of neurotransmitters into brain tissue. A steady rate of endocytosis of carbon particles and fluorescent latex beads, 0.2–1 urn in diameter, was observed in cultured meningioma cells. Such endocytosis was inhibited by cyto‐chalasin B indicating the active participation of intracellular microfilaments. Similar endocytosis has been observed in normal leptomeninges in vivo. The results of this study suggest that meningioma cells in culture reflect the barrier functions of the pia mater and may be used as a model to further investigate the functions of the pia mater.
The glial reaction in closed head injuries
Authors: CROOKS D. A. , SCHOLTZ C. L. , VOWLES G. , GREENWALD S. , EVANS S.
Published: May 2008

The development of the glial reaction in human closed head injury has been investigated using morphometry and statistical analysis. The brains of eight individuals that survived less than 48 h following closed head injury were analysed using immunoperoxidase for glial fibrillary acidic protein (GFAP). Controls were eight patients without neurological disease. The density of reactive astrocytes was estimated in 25 fields in each of 10 different areas sampled bilaterally avoiding the subpial and subependymal zones, and the perivascular white matter. There was great variation between the zones within and between groups, and considerable variation between individuals. The raw data were expressed as logarithms averaged and analysed using the median and non‐parametric statistics. The corpus callosum in the head injury group showed the highest densities of reactive astrocytes, particularly in the splenium which achieved statistical significance using the non‐parametric tests. This pattern was not reproduced in the control group. Although there was overlap between the head injured and control individuals, the head injury group had relatively higher densities in all zones, and showed an overall increase in the density of reactive astrocytes. This achieved statistical significance in the corpus callosum, the occipital subcortical white matter, and the cerebellum. This study has shown that the glial reaction is often prominent in the corpus callosum irrespective of the presence of a primary lesion although the pattern varies from case to case.
Distribution of Alzheimer's disease amyloid protein precursor in normal human and rat nervous system
Authors: CORIA F. , MORENO A. , TORRES A. , AHMAD I. , GHISO J.
Published: May 2008

Alzheimer's disease and cerebral amyloid angiopathies (CAA) are clinically heterogeneous diseases, but pathogenically related by the deposition of βA4‐amyloid in the brain in the form of neuritic plaques and/or vascular infiltrates. Antibodies directe against the N‐terminal region of the predicted sequence of the βA4 amyloid protein precursor (APP) were used to investigate the cellular distribution of this protein in the brain of normal humans and rats. We found a widespread presence of APP throughout the nervous tissue, including neurons, blood vessels, menigeal membranes, choroid plexus and ependymal cells. The highest APP immunoreactivity in both species was found in neuronal cell bodies and their processes, and around blood vessels. These findings may account for the clinical, pathological and aetiological differences found among the βA4‐amyloidosis.
The behaviour of meningeal cells following glial cell transplantation into chemically‐induced areas of demyelination in the CNS
Authors: FRANKLIN R. J. M. , CRANG A. J. , BLAKEMORE W. F.
Published: May 2008

Following transplantation of cultures of CNS glia containing leptomeningeal cells into ethidium bromide‐induced demyelinating lesions, meningeal cells adopt either compacted or diffuse arrangements. The compacted arrangements involved no interactions with other cellular components of the remyelinating environment, and were particularly prominent following transplantation of cultures containing a high proportion of fibronectin‐positive meningeal cells. The diffuse arrangements involved interactions with astrocytes, Schwann cells and endothelial cells, and contributed to a fragmented appearance of the lesion. Such observations indicate that meningeal cell contamination should be avoided when attempts are being made to repopulate glial‐deficient lesions in the CNS by transplanting central glial cells, since their effect is to partition the glial environment.
Dying back type axonal degeneration of sensory nerve terminals in muscle spindles of the gracile axonal dystrophy (GAD) mutant mouse
Authors: ODA K. , YAMAZAKIT K. , MIURA H. , SHIBASAKI H. , KIKUCHI T.
Published: May 2008

A disorder of the gracile axonal dystrophy (GAD) mutant mouse is characterized by a neuro‐muscular disease with sensory ataxia (detectable 30 days after birth) and paresis of the hind‐limbs (detectable at 80 days). In the sensory ataxia stage, histological study of the primary sensory system shows that, in addition to the lesions in the central nervous system, peripherally projecting axons have also started to degenerate at their distal ends in muscle spindles. Although the structure of Ia fibre endings appear normal until 15 days after birth, initial changes in the annulo‐spiral structure are detected around the 20th day by a degeneration of the terminal axons. Degeneration then progressed proximally and the secondary endings also start to degenerate. Neuron cell bodies located in the dorsal root ganglia are morphologically intact until the later stages. Chronological studies indicate that, although axonal degeneration progresses throughout life, it is accentuated during the rapid somatic growth period. Around 50 days of age, transient regeneration takes place at axonal endings when somatic growth has attained a plateau. Such primary sensory endings tend to be restored by fine, multiple axons which gain access to the intrafusal fibres through the original endoneurial tubes. Ultrastructural observations at the fully affected stage show intrafusal muscle fibres lying scattered within spindles due to loss of the fine network of inner capsule layers and an almost complete loss of sensory endings from the surface of intrafusal muscle fibres. These results indicate that this mutant mouse is a useful model for naturally occurring ‘dying back’ type axonal degeneration or ‘central and peripheral distal axonopathies', and would provide significant information about the complete evolution of the pathological processes involved.
The binding of basic fibroblast growth factor to ischaernic neurons in the rat
Authors: KATO T. , NAKANO S. , KOGURE K. , SASAKI H. , KOIWAI K. , YAMASAKI Y. , KATAGIRI T. , SASAKI H.
Published: May 2008

Transient occlusion of the right middle cerebral artery for 15 min produced a small ischaemic lesion in the dorsal portion of the right striatum in rats as seen on days 3, 7 and 14 post‐operatively. The lesions consisted mainly of reactive astrocytes and ‘ischaemic neurons’ with chromatin‐condensed (pyknotic) nuclei and homogeneously eosinophilic cytoplasm. The incubation of tissue sections with basic fibroblast growth factor (bFGF) followed by anti‐bFGF, or with biotinylated bFGF without anti‐bFGF, labelled virtually all ischaemic neurons, indicating that bFGF had bound to the latter. The pretreatment of sections with heparitinase prevented the binding of bFGF to these cells, suggesting that the chemical substrate for the bFGF binding was heparan sulphate. In light of the findings that many normal‐looking neurons were observed in the corresponding portion of the right striatum in most rats on post‐operative days 28 and 90, the appearance of bFGF‐binding sites in ischaemic neurons may contribute to the repair process of injured neurons.