bluuebunny/crossref_metadata_2025 huggingface dataset:
ANNOTATION: AN ANIMAL MODEL OF CEREBRAL ANEURYSMS
Authors: HAZAMA F. , HASHIMOTO N.
Published: May 2008

Cerebral aneurysms were induced experimentally in rats by ligating the common carotid artery on one side, making the animals hypertensive, and feeding them the lathyrogen β‐aminopropionitrile. On analysis of this experimental model, haemodynamic stress, hypertension and metabolic disorder of the connective tissue proved to be of primary importance as aetiological factors in the development of cerebral aneurysms. The experimentally induced cerebral aneurysms resemble those in man both in location and in microscopic structure; they can thus be regarded as a good model for the study of the pathogenesis of cerebral aneurysms. The initial changes leading to the formation of aneurysms occurred on the distal side of major artery branches adjacent to the apex, but distal to the intimal pad. It is proposed that degenerative changes in the internal elastic lamina and muscle cells of the media, caused by haemodynamic stress at vessel branches and intimal pads, are the basis for aneurysm formation.
SELECTIVE INFECTIONS OF OLFACTORY AND RESPIRATORY EPITHELIUM BY VESICULAR STOMATITIS AND SENDAI VIRUSES
Authors: LUNDH B. , KRISTENSSON K. , NORRBY E.
Published: May 2008

Following intranasal instillation of vesicular stomatitis virus (VSV) in mice there was an extensive infection of the olfactory epithelium in contrast to a minimal involvement of the respiratory epithelium. Sendai virus (SV), on the other hand, caused an extensive infection of the respiratory epithelium and only minimal infection of the olfactory mucous membrane. VSV budded from basolateral surfaces of supporting cells and olfactory neurons, but not from their apical surfaces or the ciliated bulbous endings of the olfactory neuron dendrites. This asymmetric release of VSV favoured neuroinvasion. The virus spread along the olfactory nerves to the glomeruli in the olfactory bulbs after which it propagated transneuronally into the rest of the brain. SV budded only from the apical surface of respiratory epithelial cells, was released into the air passages, and there were no signs of invasion into the olfactory bulbs. Inoculation of the olfactory mucous membrane is a useful procedure for studies on selectivity of attack on peripheral neurons by viruses and on mechanisms of virus invasion of the nervous system in vivo.
NEUROPATHOLOGY AND NEUROVIRULENCE OF CANINE DISTEMPER VIRUS PLAQUE ISOLATES IN THE HAMSTER
Authors: ALLEN I. V. , COSBY S. L. , KIRK J. , MARTIN S. J. , DINSMORE S.
Published: May 2008

Neuropathlogy and neurovirulence of canine distemper virus plaque isolates in the hamster

The relationship between neuropathologiesl abnormalities, antibody response and neurovirulence of plaque isolates has been studied in an experimental model of canine distemper in the hamster. Genetic virus variance influenced neurovirulence and the experimental evidence supports the hypothesis that the mechanism of this effect may be through the modulating effect of circulating antibody. Large plaque virus (LPV) produced severe encephalitis with little early antibody response and a high degree of pathological abnormality. Small plaque virus (SPV) produced mild chronic encephalitis and early antibody response. Microscopically, histological abnormalities in this group were qualitatively similar to those seen with LPV but generally of lesser degree. Immunosuppression in SPV infected animals increased the severity of the encephalitis, reflected by the increase in inflammation and inclusion formation. Combined SPV and LPV infection produced high antibody levels and less severe disease than LPV infection alone with an intermediate pattern of histological abnormality.
SINUS HISTIOCYTOSIS WITH MASSIVE LYMPHADENOPATHY PRESENTING AS A MENINGIOMA
Authors: CAREY M. P. , CASE C. P.
Published: May 2008

Sinus histiocytosis with massive lymphadenopathy presenting as a meningioma

This report documents a case of sinus histiocytosis with massive lymphadenopathy (SHML) which was unusual in that it produced a localized mass on the intracranial dura, simulating a meningioma. The clinical, histological and ultrastructural features of this case are presented.
SCHWANN CELL RESPONSES DURING REGENERATION AFTER ONE OR MORE CRUSH INJURIES TO MYELINATED NERVE FIBRES
Authors: OHARA SHINJI , IKUTA FUSAHIRO
Published: May 2008

Schwann cell responses during regeneration after one or more crush injuries to myelinated nerve fibres

The responses of Schwann cells during regeneration of myelinated nerve fibres were studied ultrastructurally in the distal segment of mouse phrenic nerve after a single or repeated localized crush injury. Chronological observations on nerves after a single crush confirmed the occurrence of myelination of only single regenerating axons among many that appeared in individual Bungner bands. The redundant axon sprouts often showed the structural features of degeneration and decreased in number with time. During the process, supernumerary Schwann cells not related to myelin formation were produced. They commonly failed not only to make a one–to–one relationship with an axon, but they also failed to acquire a new basal lamina of their own. With time, they showed shrinkage of their cytoplasm and became arranged circumferentially around the myelinating axon with unipolar or bipolar cytoplasmic processes.

Electron microscopic, quantitative assessment of the nuclear population of Schwann cells following repeated crushes up to four times, clearly indicated a progressive and predominant increase in the number of the supernumerary Schwann cells with the number of crushes. Also, they were found to form separate concentric cytoplasmic lamellae around the myelinating axons, developing structures resembling onion–bulbs.

It was concluded that essentially the same regenerating process as that observed after a single crush was repeated following re–crush, thereby resulting in the successive accumulation of supernumerary Schwann cells around a myelinating axon.
NEUROPATHOLOGY OF ACQUIRED IMMUNODEFICIENCY SYNDROME
Authors: GONZALES M. F. , DAVIS R. L.
Published: May 2008

Neuropathology of acquired immunodeficiency syndrome

The nervous system is involved in the acquired immunodeficiency syndrome (AIDS) by infections and infestations, by neoplasms, and by several diseases of uncertain pathogenesis. The most common pathological abnormalities are the changes associated with the HIV agent itself, the ‘HIV subacute encephalitis’; the most specific change is demyelination with multinucleate giant cells. Cytomegalovirus (CMV) is the most common secondary virus, but progressive multifocal leucoencephalopathy (PML) is more frequently seen at biopsy. Toxoplasmosis is the most common cause of abscess formation, but fungal infections, especially by cryptococcus, are more often the cause of meningitis. Mycobacterial infections and other opportunistic organisms are relatively rarely seen in the CNS. A vacuolar myelopathy of unknown pathogenesis is seen in AIDS; it involves the dorsal and lateral columns and the thoracic spinal cord most prominently. Endarteritis of unknown cause with resultant infarction is seen in children. Primary CNS lymphoma accounts for a major percentage of the lymphomas seen in AIDS; they are high grade tumours, are most often multiple, and are of B‐cell origin. Metastatic Kaposi's sarcoma is very rare. Several peripheral neuropathies occur in AIDS, and recently a myopathy with small rod bodies has been reported.
PATHOLOGY OF THE CENTRAL NERVOUS SYSTEM IN 40 CASES OF ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS)
Authors: GRAY F. , GHERARDI R. , KEOHANE C. , FAVOLINI M. , SOBEL A. , POIRIER J.
Published: May 2008

Pathology of the central nervous system in 40 cases of acquired immune deficiency syndrome (AIDS)

The central nervous system was examined in 40 AIDS patients who died between August 1982 and 1987. The cases included two children born to intravenous drug abusers and 38 male adults.

The brains of eight patients who had no clinical or radiological evidence of central nervous system involvement showed non‐specific changes which included microglial nodules, perivascular mononuclear cuffs, mineralization of blood vessels and granular ependymitis.

In 32 brains from patients with neurological symptoms, toxoplasmosis was the most frequent finding (19 cases) manifested by multifocal, necrotic lesions or a diffuse pseudo‐encephalitic process. Other opportunistic infections included cytomegalovirus (eight cases), progressive multifocal leucoencephalopathy (two cases), cryptococcosis (one case), aspergillosis (one case), multiple bacterial microabscesses (one case) and Mycobacterium avium intracellular (one case). Two patients had cerebral lymphoma. Subacute encephalitis with white matter lesions and multinucleated giant cells characteristic of HIV infection was present in 15 cases.

Various combinations of all these infections were encountered in the same brain, sometimes in the same area and, occasionally, in the same cell.
A CLINICO–PATHOLOGICAL STUDY OF HERPES SIMPLEX ENCEPHALITIS
Authors: KENNEDY P. G. E. , ADAMS J. HUME , GRAHAM D. I. , CLEMENT G. B.
Published: May 2008

A clinico‐pathological study of herpes simplex encephalitis

A retrospective clinical and pathological analysis has been performed of 24 cases of herpes simplex virus encephalitis (HSE) seen at the Institute of Neurological Sciences, Glasgow, between 1972 and 1985. All patients had been diagnosed on the basis of isolation of herpes simplex virus (HSV) from, and/or the demonstration of characteristic histological changes of acute necrotizing encephalitis (ANE) in brain biopsy and/or autopsy tissue. Clinical presentation on admission included a prodromal influenzalike illness (46%), sudden onset of headache and confusion (54%), meningism (38%), deep coma (42%), aphasia (54%) and focal neurological signs (79%). Seizures occurred in 46% of cases during the course of the illness. Of the 24 cases, 14 (58%) died and 10 (42%) survived. Intravenous acyclovir treatment was associated with the best prognosis.

Cerebral biopsy of one temporal lobe was performed in 22 cases and in 19 of these a positive histological diagnosis of HSE could be made. HSV was isolated from 15 of the 19 (79%) biopsied cases in whom virus isolation was attempted. Only seven out of the 15 cases (47%) in which immunofluorescence assays for HSV antigens were performed were unequivocally positive. Herpes simplex virus was isolated in culture from all cases which were negative by immunofluorescence.

Immunocytochemical analysis on tissue sections of five representative brain biopsies demonstrated the presence of HSV antigens in some astrocytes, neurons and macrophages especially within areas of inflammatory infiltration. In situ hybridization experiments with a cloned HSV DNA probe demonstrated viral RNA in astrocytes, neurons and macrophages in two human biopsies and mouse brains in areas broadly corresponding to the distribution of viral antigen labelling. The combined immunocytochemical and in situ hybridization procedure showed that many but not all of the cells containing viral RNA also contained HSV antigens, indicating a productive infection in these double‐labelled cells.
IMMUNOCYTOCHEMICAL CHARACTERIZATION OF PRIMARY GLIAL CELL CULTURES FROM NORMAL ADULT HUMAN BRAIN
Authors: NEWCOMBE J. , MEESON A. , CUZNER M. L.
Published: May 2008

Newcombe J., Meeson A. & Cuzner M. L. (1988) Neuropathology and Applied Neurobiology 14, 453–465

Immunocytochemical characterization of primary glial cell cultures from normal adult human brain

Primary cultures were established from autopsy or biopsy samples of normal adult human brain and characterized by immunocytochemical techniques. Initially, macrophages were the predominant cell type adhering to the substratum, but as their number fell that of glial cells increased. Oligodendrocytes comprised 30% of the glial population in white matter cultures, and their perikarya and elongated processes were immunostained with antibodies directed against galactocerebroside and four myelin proteins. In white and grey matter cultures, process–bearing astrocytes and small numbers of polygonal astrocytes were stained with antibodies against glial fibrillary acidic protein and glutamine synthetase. Fibroblasts started to appear at 3 weeks and proliferated to form a monolayer beneath glial cells by 5 weeks. Glia began to die in the 6th week. These primary cell cultures of white or grey matter can be used to study the properties of glial cells from normal or pathological adult human brain.
ENHANCEMENT OF DEMYELINATION IN THE CENTRAL NERVOUS SYSTEM OF SEMLIKI FOREST VIRUS INFECTED MICE AFTER PRETREATMENT WITH MURAMYL DIPEPTIDE
Authors: ILLAVIA S. J. , WEBB H. E. , COLOVER J.
Published: May 2008

Illavia S. J., Webb H. E. & Colover J. (1988) Neuropathology and Applied Neurobiology 14, 483–493

Enhancement of demyelination in the central nervous system of Semliki Forest virus infected mice after pretreatment with muramyl dipeptide

Semliki Forest virus infections in mice produce an encephalitis with demyelination. If before giving the virus the mice are treated with muramyl dipeptide in Freund's incomplete adjuvant, there is a significant increase in demyelination. If ovalbumin is added to the above and then followed after an interval by a second dose of ovalbumin and finally by the virus, the demyelination is further, but only marginally increased. The addition of ovalbumin without muramyl dipeptide in the schedule appears to increase the number of infiltrating cells and to a lesser extent the perivascular cuffing, but does not increase the demyelination as compared to that obtained when Semliki Forest virus is given on its own.
CORTICAL AND SUBCORTICAL ARGYROPHILIC GRAINS CHARACTERIZE A DISEASE ASSOCIATED WITH ADULT ONSET DEMENTIA
Authors: BRAAK H. , BRAAK E.
Published: May 2008

Cortical and subcortical argyrophilic grains characterize a disease associated with adult onset dementia

Unusual cytoskeleton abnormalities were found in the brains of 28 individuals afflicted with adult onset dementia. Most conspicuous were small spindle‐shaped argyrophilic grains loosely scattered throughout the neuropil. Additionally, coiled bodies of silver‐stained filaments were encountered, mainly located within the white matter close to the cortical grey matter. Argyrophilic grains and coiled bodies contained dense accumulations of straight filaments with a diameter of about 9 nm.

The argyrophilic grains were found in abundance within sector CA1 of the Ammon's horn and layer Pre‐β of the entorhinal region. A slightly less dense scattering of the grains occurred in layer IIIab of the adjoining temporal isocortex, insular cortex and orbitofrontal cortex. The basolateral amygdaloid complex and the hypothalamic lateral tuberal nucleus were the most affected subcortical structures. Deeper brain stem nuclei merely showed a sparse number of grains or were devoid of them.

Eighty brains of demented individuals were examined. Forty‐eight of them showed the features of Alzheimer's disease and four showed the features of Pick's disease. Twenty‐eight cases revealed the abnormalities under consideration. Ten showed exclusively argyrophilic grains and coiled bodies, while 16 also had neuritic plaques, neurofibrillary tangles, and neuropil threads. One of the 28 cases was associated with Parkinson's disease and one showed features of both Parkinson's and Alzheimer's disease. Twenty brains of non‐demented individuals of about the same age and devoid or almost devoid of Alzheimer changes were used as controls. None of the control brains showed the presence of argyrophilic grains and coiled bodies. These changes, therefore, are considered the morphological substrate of an unknown disease associated with adult onset dementia.
BOOK REVIEWS
Authors: KAPUR NARINDER , BELL JEANNE E. , POLKEY C. E.
Published: May 2008

Book reviewed in this article:

Walsh, K. Neuropsychology. A Clinical Approach 2nd Edition

WALSH, K.W. (1985) Understanding Brain Damage.

Ounstead, C, Lindsay, J. & Richards, P. Temporal Lobe Epilepsy–A Biographical Study 1948–1986 Clinics in Developmental Medicine No 103.

Milhorst, T. H. Cerebrospinal Fluid and the Brain Oedemas Neuroscience Society of New York
MITOCHONDRIA–RELATED ENCEPHALOMYOPATHIES
Authors: GOEBEL H. H. , BORNEMANN A. , REICHMANN H.
Published: May 2008

Owing to advances in morphological and biochemical techniques, the mitochondria–related myopathies and encephalomyopathies have emerged as a still rapidly growing group of primary and secondary metabolic disorders, which may extend from infancy to late adulthood. Impairment of the biochemically diversified mitochondria is reflected in an enormous number of deficiencies, often affecting several mitochondrial enzymes in the same patient; morphologically abnormal mitochondria are common and are thus not specific to individual mitochondrial enzyme deficiencies. Skeletal muscle biopsies have provided a wealth of data through histological and histochemical studies and from isolated mitochondria. As a similar abundance of biochemical and morphological findings has not been obtained from brain tissue in mitochondrial encephalomyopathies, investigation of these disorders is still in its infancy; interpretation of these conditions and their encephalopathic components has largely been based on comparison of data not derived from brain tissues. Therefore, it has been, and still is, largely the link between an encephalopathy and an associated mitochondrial myopathy that identifies the brain lesions as clinical and morphological expressions of a mitochondrial defect. As enzyme histochemical and electron microscopic investigations of mitochondrial encephalopathies have not yielded a comparable rich spectrum of morphological findings, it is conceivable that the spectrum of mitochondrial encephalopathies may be much larger than defined by the hitherto identified encephalomyopathies. This may be especially so when the myopathic component is of minor nosological significance.
ULTRASTRUCTURE OF AXOTOMIZED ALPHA AND GAMMA MOTONEURONS IN THE CAT THORACIC SPINAL CORD
Authors: JOHNSON I. P. , SEARS T. A.
Published: May 2008

Using horseradish peroxidase as a retrograde marker, the ultrastructural response of alpha and gamma motoneuronal cell bodies in the cat thoracic spinal cord has been compared 1–8 days following intercostal nerve transection and ligation. By light microscopy, reduction of Nissl body size, together with nuclear and nucleolar alterations were seen in alpha motoneurons 4–8 days following axotomy, but not at any stage in axotomized gamma motoneurons. In the electron microscope, disorganization of Nissl body ultrastructure was seen in both alpha and gamma motoneurons 2 days following axotomy. Only in alpha motoneurons, however, did these disorganized Nissl bodies subsequently fragment into smaller pieces. Both alpha and gamma motoneurons lost synapses following axotomy, but the proportional loss from gamma motoneurons was two–fold greater than that from alpha motoneurons. Loss of synaptic terminals with flattened synaptic vesicles was two–fold higher than that of synaptic terminals with round synaptic vesicles from axotomized gamma motoneurons, whereas axotomized alpha motoneurons lost both types of synaptic terminal equally.
CHRONIC EXPERIMENTAL ALLERGIC NEURITIS IN LEWIS RATS
Authors: ADAM A. M. , ATKINSON P. F. , HALL S. M. , HUGHES R. A. C. , TAYLOR W. A.
Published: May 2008

An experimental chronic relapsing demyelinating neuropathy was produced by immunizing adult Lewis rats with bovine myelin in low (2–5 mg) and high (5 mg) doses, with and without Mycobacterium tuberculosis in the adjuvant. Each regime produced a similar disease course: acute severe hind limb weakness was followed by apparent recovery and then reappearance of mild neurological deficit with occasional spontaneous exacerbations. The partially recovered animals were relatively resistant to reimmunization with myelin. Immunization of four–week–old rats with myelin in complete adjuvant produced disease with a similar course. Subsequent immunization of these juvenile rats with adjuvant alone precipitated exacerbations. In the late stages, the prominent changes in peripheral nerves and nerve roots were axon loss, axonal regeneration and remyelination while inflammatory cell infiltration was confined to occasional foci. Onion bulb formation was extremely common in the dorsal root ganglia and affected in particular the nerve fibres close to the dorsal root ganglion cells. The cells forming the onion bulbs resembled the satellite cells surrounding the axon hillocks. Onion bulb formation also occurred in the portion of the ventral roots adjacent to the dorsal root ganglion but was rare elsewhere. Immunocytochemistry revealed only occasional lymphocyte infiltration but there was increased Class I and Class II MHC antigen expression throughout the peripheral nervous system. The results are relevant to the interpretation of biopsies from patients with chronic demyelinating neuropathy of possible inflammatory or autoimmune origin.
A COMPARATIVE IMMUNOCYTOCHEMICAL STUDY OF HUMAN CEREBELLAR CORTEX IN X–CHROMOSOME–LINKED COPPER MALABSORPTION (MENKES‘ KINKY HAIR DISEASE) AND GRANULE CELL TYPE CEREBELLAR DEGENERATION
Authors: GOTO S. , HIRANO A. , ROJAS–CORONA R. R.
Published: May 2008

A comparative immunocytochemical study on the cerebellar cortex with X–chromosome–linked copper malabsorption (X–cLCM) and granule cell type cerebellar degeneration (gc–CD) was carried out by using specific monoclonal antibodies to synaptophysin (SY) and glial fibrillary acidic protein (GFAP). In X–cLCM cases, marked depletion of SY–immunoreactivity (IR) and reduction in number of SY–positive glomeruli were seen in the molecular and granular layers, respectively. Abnormal Purkinje cells occasionally showed moderately strong SY–IR having a fine granular pattern. Proliferation of GFAP–positive cells was observed in the granular and Purkinje cell layers. In the gc–CD case, SY–positive materials were coarsely distributed in a less dense fashion in the molecular layer as compared to a normal control. Purkinje cell perikarya did not show SY–IR. In the gc–CD granular layer, SY–IR appeared to have a coarsely punctate pattern, whereas immunoreactive glomeruli were almost completely absent. A number of GFAP–positive Bergmann cells was observed in the Purkinje cell layer and their fibres were densely and irregularly distributed in the molecular layer, whereas the granular layer was devoid of GFAP–positive cells.

We present an immunocytochemical study of the X–cLCM and gc–CD cerebellar cortices, discuss the possible pathogenic mechanisms occurring in these diseases and discuss the usefulness of the SY–immunostaining technique for visualization of axon terminal involvement in these pathological conditions.
EXPERIMENTAL INTRACEREBRAL HAEMATOMA IN THE RAT: SEQUENTIAL LIGHT MICROSCOPICAL CHANGES
Authors: JENKINS A. , MAXWELL W. L. , GRAHAM D. I.
Published: May 2008

In a small animal model of controlled intracerebral haemorrhage, changes within the haematoma and surrounding tissues were examined by light microscopy in toluidine blue stained semithin sections. Groups of animals were killed at 2, 6, 15, 24 and 48 hours, 2, 4, 8 and 14 days, and 3 months survival. Sequential changes in neurons, glia and leucocytes, together with the gradual absorption of the blood clot and its replacement by an astrocytic scar are described.
Immunolocalization of cathepsin D in the human central nervous system and central nervous system neoplasms
Authors: ROBSON D. K. , IRONSIDE J. W. , REID W. A. , BOGUE P. R.
Published: May 2008

The cellular distribution of the lysosomal proteinase cathepsin D was studied in a series of 76 neoplasms and 18 non‐neoplastic tissues from the human central nervous system, using a well‐characterized polyclonal antibody in a peroxidase‐antiper‐oxidase technique. In the normal and developing brain, cathepsin D is confined to neurons and choroid plexus epithelium. Strong granular cytoplasmic staining was present in neuronal and choroid plexus neoplasms, and in reactive macro‐phages. A large variety of other neoplasms also exhibited positive cytoplasmic staining, albeit usually of a weaker diffuse type. Cathepsin D cannot be considered a specific marker for neuronal or choroid plexus neoplasms, but the antiserum used in this study may be of value in antibody panels for the investigation of these tumours. Its localization may also be of value in embryological studies, particularly in the cerebellum, and in investigations of steroid hormone receptor‐associated proteins in meningiomas and Schwannomas.
Regeneration of nerve fibres in the anterior medullary velum of neonatal and weanling rats
Authors: HUTCHINSON S. P. , McCONNELL P.
Published: May 2008

The responses to injury of myelinated central axons in neonatal (5‐day) and weanling (30‐day) rats were compared, using the trochlear nerve fibres in the anterior medullary velum (AMV) as an experimental system. In intact animals, fibres of the trochlear nerve decussate completely in the AMV, to enter the contralateral nerve. Sprouting from proximal axon stumps was seen within 36 h after injury in silver‐stained, whole mounts of mid‐sagittally lesioned AMVs from weanlings. Subsequent growth produced a tangled axon mass which persisted until 15–20 days post‐lesion (d.p.l.) but then began to degenerate. By 50 d.p.l, the majority of surviving axons looped within the AMV to enter the ipsilateral trochlear nerve; few axons remained growing randomly within the AMV. Axonal debris persisted within the velum 50 d.p.l. In neonatal rats, lesioned trochlear axons initially developed axon sprouts, but then degenerated with rapid clearance of debris, leaving the AMV devoid of both axons and degeneration products by 6 d.p.l. From 8 d.p.l., the velum became repopulated by axons which either grew randomly or looped to enter the ipsilateral peripheral nerve. Both patterns of axon growth were still observed 50 d.p.l. In both experimental groups, horseradish peroxidase injection to the right superior oblique muscle 40 d.p.l. indicated that at least some of the looping fibres observed within the lesioned AMVs originated in the ipsilateral trochlear nucleus. The origin of those axons growing randomly within the AMVs of neonatally‐lesioned animals is unknown. The results are discussed with reference to current ideas concerning regeneration‐inhibiting elements in the CNS, and regeneration‐promoting factors in the PNS.
Ubiquitinated eosinophilic granules in the inferior olivary nucleus
Authors: KATO S. , HIRANO A. , SUENAGA T. , YEN S. H.
Published: May 2008

Ubiquitinated ìntracytoplasmic eosinophilic granules were found in the inferior olivary neurons of 99 normal individuals. The granules, ranging from 1 to 8 μM in diameter, were round and appeared in groups. Their number increased significantly with ageing. The frequency of the granules in 12 patients with Alzheimer's disease or spinocerebellar degeneration did not differ from that in normal subjects. The ubiquitinated eosinophilic granules can be considered to represent age‐related changes in the inferior olivary neurons.
Selective degeneration of cerebellar cortical neurons caused by cycad neurotoxin, L‐β‐methylaminoalanine (L‐BMAA), in rats
Authors: SEAWRIGHT A: A. , BROWN A. W. , NOLAN C. C. , CAVANAGH J. B.
Published: May 2008

Both the racemate and the L‐form of BMAA (β‐methylami‐noalanine), when injected intraperitoneally into young rats, produced acute signs of cerebellar dysfunction and degeneration of cerebellar stellate, basket, Purkinje and Golgi cells, but not granule cells. Degenerative changes were also occasionally seen in cerebellar roof nuclei which may be secondary in nature. No other changes were found in the remainder of the central nervous system. The doses of the L‐form of BMAA producing these changes were from 6 to 14 μmol/g body weight, i.e. the lower and upper levels of the dose range used by Vega and Bell (1967)* and equivalent to 75 and 183 mg/rat. Doses of 1 to 4 mg/g body weight of the racemate were given to young rats less than 100 g in weight, but no changes were apparent after daily doses of the racemate of 0.5 mg/g body weight. Damage to cerebellar neurons is considered to be the result of excitotoxic activity. All cells showing degeneration are GABAergic, although not all are known to possess N‐methyl‐D‐aspartate (NMDA) receptors. The present finding of selective cerebellar neuron damage may not conflict with the earlier findings of others, but our results suggest that L‐BMAA has unusual glutamate receptor binding properties.
Peculiar changes in Rosenthal fibres in an atypical astrocytoma
Authors: RADNER H. , KLEINERT R. , VENNIGERHOLZ F. , DENK H.
Published: May 2008

A 50‐year‐old female patient died of an unbeatable glioma apoplecticum. At autopsy a strongly vascularized glial tumour was found. The criteria for malignancy according to the WHO classification were only partially fulfilled by this tumour which displayed morphological features of an astrocytoma but could not be further subclassified. By light microscopy, angioma‐like vascular proliferations, large cells with brightly eosinophilic cytoplasm, and small cells with hyperchromatic nuclei were found. Most large cells had vesicular, excentrically placed nuclei and contained fibrillary whorls or amorphous, irregular cytoplasmic inclusions. By immunohistochemical staining, using antibodies to glial fibrillary acidic protein (GFAP) the fibrillary whorls were identified as aggregates of glial filaments. The amorphous inclusions lacked GFAP immunoreactivity and appeared in the electron microscope as electron dense material surrounded by a dense network of glial filaments. The abnormal perikaryal inclusions of these atypical astrocytoma cells appeared to be peculiar alterations of Rosenthal fibres closely mimicing Mallory bodies.
Glial and neuronal differentiation in the human fetal brain 9–23 weeks of gestation
Authors: WILKINSON M. , HUME R. , STRANGE R. , BELL J. E.
Published: May 2008

Glial and neuronal differentiation in the human fetal brain 9–23 weeks of gestation. Nineteen human fetal brains ranging from 9–23 weeks of gestation were examined immunocytochemically for evidence of glial and neuronal differentiation. Radial glia were positive for vimentin and glial fibrillary acidic protein (GFAP) throughout the age range. SlOO‐positive cells which were presumed to be astrocytes were present from 9 weeks; they were always more widespread in the cerebrum and the brainstem than GFAP‐positive mature astrocytes, which could be detected with certainty only at 14 weeks. Carbonic anhydrase II (CA II)‐positive oligodendrocytes were present in the brainstem in small numbers from 17 weeks. Neuronal fibre tracts in the cerebrum were positive for 160 kD phosphorylated neurofilament protein (BF10) from 9 weeks, but negative for 200 kD phosphorylated neurofilament protein (RT97) and for 70 and 200 kD non‐phosphorylated neurofilament protein (NFP) whereas most tracts in the brainstem were positive for BF10 from 9 weeks and positive for the other neurofilament proteins from 14 weeks. Corticospinal tracts differed in remaining negative for neurofilament proteins other than BF10, which showed positive reaction throughout. Perikarya of differentiated neurons in all areas of the brain were neurofilament‐negative but neuron specific enolase (NSE)‐positive. Germinal eminence cells were focally vimentin‐positive from 15 weeks, focally GFAP‐positive from 17 weeks, and negative for all NFP and for NSE. The value of a short fixation time and pretreatment with trypsin in the immunocytochemical demonstration of GFAP is stressed.
Role of the basement membrane in the regeneration of skeletal muscle
Authors: CALDWELL C.J. , MATTEY D. L. , WELLER R. O.
Published: May 2008

Role of the basement membrane in the regeneration of skeletal muscle. In many experimental models of skeletal muscle damage and in human muscle disease, empty basement membrane tubes remain following the destruction of muscle fibres. In the present study we test the hypothesis that the empty basement membrane tubes play an essential role in the orientation of regenerating muscle fibres. Two groups of 15 Wistar rats were used. In one group, aqueous barium chloride (BaCl2) solution was injected into the right quadriceps muscle; in the other group, freshly prepared 2% trypsin solution was similarly injected. The different stages of muscle cell necrosis and regeneration were observed by histology, by immunofluorescence using an anti‐basement membrane antibody, and by transmission (TEM) and scanning electron microscopy (SEM) in animals killed 1–77 days following injection. Although there was muscle fibre necrosis at sites of BaCl2 injection, empty basement membrane tubes were well preserved. Myoblasts grew along the empty basement membrane tubes and by 77 days, the regenerated muscle fibres at the site of the injection were well orientated. Trypsin not only destroyed muscle fibres but also destroyed the basement membrane tubes; in the early stages of regeneration the myoblasts were disorientated but by 77 days, regeneration was comparable to that seen in the barium chloride injected muscle. The results of this study suggest that preservation of empty basement membrane tubes is not essential for the orientation of regenerating myoblasts in skeletal muscle.
Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis
Authors: TROOST D. , van den OORD J. J. , JONG J. M. B. VIANNEY DE
Published: May 2008

In order to test the hypothesis that the immune system plays a role in the pathogenesis of amyotrophic lateral sclerosis (ALS), the cellular composition of the spinal cord inflammatory infiltrate was analysed in eight cases of sporadic ALS by a panel of monoclonal antibodies. The majority of the many diffusely scattered lymphocytes seen in the anterior and lateral corticospinal tracts and anterior horns belonged to the suppressor/cytotoxic T‐cell subset and were admixed with variable numbers of macrophages. Helper‐inducer T‐cells were rare and B‐cells were conspicuously absent. Compared to controls, ALS specimens exhibited an increase in major histocompatibility complex (MHC) products or human leucocyte antigens (HLA) in the corticospinal tracts and anterior horns. HLA‐ABC antigens were expressed in the honeycomb pattern of the glial matrix of the spinal cord, and HLA‐DR antigens were strongly expressed by large dendritic cells. In addition, macrophages and endothelial cells were labelled by HLA‐DR. These findings suggest that an autoimmune process or infectious agent may play a role in ALS.
The use of monosodium glutamate in identifying neuronai populations in mice infected with scrapie
Authors: FOSTER J. D. , SCOTT J. R. , FRASER H.
Published: May 2008

The excitatory amino‐acid, monosodium glutamate, which causes degeneration in the retinal ganglion cells in neonatal mice, was used to investigate the transport of scrapie within optic nerve axons. In treated mice, there was prolongation of the incubation period following intraocular infection with the ME7 strain of scrapie, and a decrease in the severity of retinopathy after intracerebral infection with the 79A strain These data confirm that scrapie infection spreads along neural pathways, and demonstrate the potential use of selective neurotoxins to study pathogenesis.
Immunochemical detection of sodium channel in human tissue and cell lines
Authors: LOVE S. , BOURNE S. P. , BAINES D.
Published: May 2008

Mouse monoclonal antibodies have been raised to the C–terminal region of rat type II voltage–dependent sodium channel. One of these, designated 13A4–G4, recognizes a 260 Kd putative sodium channel protein in human fetal brain, heart and skeletal muscle, at 14–18 weeks of gestation. Faint immunoreactivity is also present in human fetal kidney but none has been detected in human fetal liver, lung or spleen. The antibody reacts in both western blots and immunocytochemical preparations with the human neuroblastoma cell lines SK–N–SH and SK–N–MC, the rhabdomyoblastoma cell line TE671, Y79 retinoblastoma cells and IPSB–18 astrocytoma cells. No 13A4–G4 immunoreactivity has been detected in several human cell lines derived from tissues that do not normally express sodium channels.
Stress protein inclusions in cerebral vessels in dialysis encephalopathy
Authors: MARTIN J. E. , MATHER K. , SWASH M. , DODD S. M. , DALE G. E. , GAROFALO O. , LEIGH P. N.
Published: May 2008

Dialysis encephalopathy, a complication of long‐term haemodialysis, is a syndrome characterized by progressive dementia, myoclonus, dysarthria and ataxia associated with high serum and brain levels of aluminium. Expression of heat‐shock or stress proteins, including ubiquitin can be induced in cell culture experiments by aluminium. We Report immunohistochemical studies of heat shock protein (HSP) expression in the frontal cortex of three patients with dialysis dementia. Immunolabelling with antibody to the 72 kD heat shock protein revealed punctate granules in most endothelial cells of cortical vessels in patients with dialysis encephalopathy. These granules, 1–5 urn in diameter, aggregated to form inclusions that resembled stress‐granules, typically induced in plant or animal cell culture by repeated insult. These granules did not express epitopes of ubiquitin. They were rare in endothelial cells in the brains of subjects dying with other neurological disorders or of non‐neurological causes. We suggest that these stress granules represent a toxic response of endothelial cells in the brain to aluminium.
Multifocal multinucleated giant cell myelitis in an AIDS patient
Authors: GENY C. , GHERARDI R. , BOUDES P. , LIONNET F. , CESARO P. , GRAY F.
Published: May 2008

A 19‐year‐old male intravenous drug abuser, was admitted to hospital with a one‐week history of lower limb weakness and urinary retention. He was known to have been HIV‐seropositive for 3 years and had been treated for cerebral toxoplasmosis. Neurological examination confirmed flaccid paraparesis with weak ankle jerks and bilateral extensor plantar responses. There was no obvious sensory deficit. Neurological examination was otherwise normal. CSF contained 63 mg/dl protein and 10 leucocytes/mm3. Myelography was normal. He died 1 month later from septic peritonitis. Neuropathological examination showed chronic lesions of toxoplasmosis in brain. Small necrotic foci with myelin loss, proliferation of microglia, macrophages and multinucleated giant cells (MGC) were disseminated in the whole spinal cord, mostly in the white matter, but the brain was spared. Immunohistochemistry demonstrated p24 and p17 HIV antigens in macrophages, MGC and microglial cells. These lesions resemble those of so called ‘multifocal giant cell encephalitis'. The present case demonstrates that HIV‐related multifocal inflammatory changes may be restricted to the spinal cord and may be a cause of myelopathy in AIDS patients.
B and T lymphocytes are affected in lysosomal disorders – an immunoelectron microscopic study
Authors: BRUCK W. , GOEBEL H. H. , DIENES P.
Published: May 2008

Circulating lymphocytes of four patients with mucopolysaccharidoses II and IIIA, four patients with juvenile neuronal ceroid‐lipofuscinosis, one patient each with glycogenosis type II, infantile neuronal ceroid‐lipofuscinosis, and Gaucher disease were classified by immunoelectron microscopy as B or T lymphocytes. Disease‐specific lyosomal inclusions as well as non‐specific lysosomal organelles, especially Gall bodies were identified in B and T lymphocytes. These non‐quantitative studies indicate that both B and T lymphocytes participate in the lysosomal storage process.
Respiratory burst activity in brain macrophages: a flow cytometric study on cultured rat microglia
Authors: BANATI R. B. , ROTHE G. , VALET G. , KREUTZBERG G. W.
Published: May 2008

A new flow cytometric method for the investigation of the respiratory burst of macrophages/ microglia isolated from neonatal rat brain has been established. Respiratory burst activity was measured quantitatively in single viable cells by the intracellular oxidation of non‐fluorescent dihydrorhodamine 123 (DHR) to fluorescent rhodamine 123. Cultured microglia exhibited high spontaneous respiratory burst activity already before stimulation. After maximal stimulation with phorbol myristate acetate, DHR oxidation rose by 40–95%. The respiratory burst activity in resident or inflammatory, i.e. thioglycolate elicited, peritoneal macrophages was significantly lower than in cultured brain macrophages suggesting a high potential of microglia for oxidative tissue destruction.
Cerebral endothelial cell infection by measles virus in subacute sclerosing panencephalitis: ultrastructural and in situ hybridization evidence
Authors: KIRK J. , ZHOU A. L. , McQUAID S. , COSBY S. L. , ALLEN D I. V.
Published: May 2008

Infection of vascular endothelium plays a central role in the pathogenesis of acute measles virus infection outside the central nervous system (CNS) but has not been described in the human CNS. An ultrastructural survey was made of blood vessels in five cases of subacute sclerosing panencephalitis (SSPE) to determine whether or not infection of cerebral vascular endothelium occurred in this persistent fatal CNS disease caused by measles virus. Morbillivirus nucleo‐capsids were found in a few endothelial cells in three necropsy cases but not in the limited tissue available from two biopsies. In a severe parenchymal lesion in one necropsied case, endothelial cells hybridized in situ with a biotinylated probe specific for the N genomic RNA of measles virus. It is concluded that human cerebral endothelium is susceptible to measles virus infection.
Multiplication of rubella and measles viruses in primary rat neural cell cultures: relevance to a postulated triggering mechanism for multiple sclerosis
Authors: ATKINS G. J. , MOONEY D. A. , FAHY D. A. , NG S. H. , SHEAHAN B. J.
Published: May 2008

Rubella virus multiplied to low titre and produced a partial cytopathic effect in rat glial cell cultures. Anti‐galactocerebroside staining showed that this cytopathic effect involved the disintegration of oligodendrocytes. A similar effect was produced following infection of myelinating neural cell cultures with rubella virus, but virus multiplication could not be detected in pure neuron cultures. Measles virus was found to multiply and produce a cytopathic effect in primary cultures of both neurons and glial cells. These results are discussed in relation to the ability of measles and rubella viruses to trigger human multiple sclerosis.
Changes in muscle plasma membranes in young mice with X chromosome‐linked muscular dystrophy: a freeze‐fracture study
Authors: SHIBUYA S. , WAKAYAMA Y.
Published: May 2008

The structure of the muscle plasma membrane of tibialis anterior muscles of X chromosome‐linked muscular dystrophy (mdx) mice was studied by the freeze‐fracture technique at 3, 7 and 14 days after birth. The ultrastructural features of the freeze‐fracture replicas of the muscle plasma membrane alterations in young mdx mice showed a decrease of orthogonal array, orthogonal array subunit particle and intramembranous particle densities on the protoplasmic face. The results are consistent with the previous studies which have shown that the orthogonal arrays are significantly decreased in number in muscle plasma membranes of adult mdx mice and in those of Duchenne dystrophy. However, the immature mdx mouse membranes at 3 days after birth contained as many orthogonal arrays as controls and did not show a statistically significant decrease (P > 0.1 by the Wilcoxon rank‐sum test). Moreover, the orthogonal arrays were also numerous in young mdx mouse muscle plasma membranes at 7 and 14 days after birth, although the density was less than that of the control mice (p < 0.01 by the Wilcoxon rank‐sum test). These changes in young mdx mouse plasma membranes may precede the later muscle fibre degeneration in this mouse dystrophy and may provide us with an additional clue to the mechanism why mdx mice scarcely show any disability despite the absence of dystrophin.
An immunohistological study of macrophages in the human fetal brain
Authors: GOULD S. J. , HOWARD S.
Published: May 2008

Brains from human fetuses of 13 to 27 weeks gestation have been examined immunohistologi‐cally for the presence of macrophages using the marker alpha‐ 1‐anti‐chymotrypsin. A preliminary study demonstrated this to be a satisfactory marker of brain macrophages, although macrophages were also weakly positive for the more specific marker MAC‐387. Macrophages were widely present within the cerebral hemispheres following their rapid accumulation between 14 and 16 weeks of gestation. They were identified in characteristic locations which, in the earliest gestation brains examined at 13 weeks, included the mid‐line of the corpus callosum, around the optic tract and at the junction of the external and internal capsules near the apex of the putamen. Subsequently, macrophages were identified in abundance in the internal and external capsules and, by 22 weeks gestation, in the periventricular tissues. Their consistent presence and distribution indicate that at least the majority of these macrophages are a normal feature of the developing brain possibly related to remodelling processes.
Inflammatory demyelinating lesions in two patients with IgM monoclonal gammopathy and polyneuropathy
Authors: VITAL A. , LATINVILLE D. , AUPY M. , DUMAS P. , VITAL C.
Published: May 2008

We Report two patients with polyneuropathy and IgM monoclonal gammopathy in whom peripheral nerve biopsy showed the widening of myelin lamellae which is characteristic of IgM paraproteinaemic neuropathy. Moreover, certain myelinated fibres were invaded by histiocytes overloaded with myelin debris, and in some instances elongated macrophage processes could be seen peeling away the myelin lamellae. The latter ultrastructural features are characteristic of inflammatory demyelinating polyneuropathies in both human and experimental pathology. Such an association has not been Reported to date in human pathology, but could explain the prevalence of inflammatory demyelinating lesions in experimental models of IgM paraproteinaemic neuropathy. These two cases seem to bridge the gap between inflammatory demyelinating polyneuropathies and polyneuropathies associated with IgM monoclonal gammopathy.
Glioblastoma multiforme of the hippocampus in advanced Alzheimer's disease
Authors: POOLE E. C. , KEPES J. J.
Published: May 2008

An 87‐year‐old woman suffered from Alzheimer's disease diagnosed 6 years prior to her death. Autopsy showed in addition to far‐advanced Alzheimer's disease, a large, partially necrotic glioblastoma occupying her right hippocampus. Occurrence of a glial neoplasm in Alzheimer's disease could well be coincidental, since both entities are fairly common in elderly individuals; it is however, uncommon for gliomas to centre on the hippocampus itself. For these reasons it is possible (although cannot be proven from a single case), that florid reactive gliosis commonly associated with Alzheimer's disease, may have played a role in eventually initiating neoplastic proliferation of astrocytes in this patient.