bluuebunny/crossref_metadata_2025 huggingface dataset:
Post–traumatic Alzheimer's disease: preponderance of a single plaque type
Authors: CLINTON J. , AMBLER M. W. , ROBERTS G. W.
Published: May 2008

The cause of Alzheimer's disease is unknown. Several factors have been proposed including head trauma. At present, the link between head injury and a subsequent neurodegenerative process is largely circumstantial, except in the case of dementia pugilistica (punch drunk syndrome) found in boxers. Recent studies have shown that the brains of boxers with this syndrome contain large numbers of ‘diffuse’ p–protein immunoreactive plaques. We supposed that this plaque type might be associated with trauma induced Alzheimer–like degeneration.

In order to test this hypothesis we have re–investigated a previously Reported case of post–traumatic premature Alzheimer's disease. Immunocytochemistry using antibodies to amyloid β–protein revealed large numbers of ‘diffuse’ non–Congophilic plaques with little or no neuritic component. A similar preponderance of this plaque type is present in the brains of boxers with dementia pugilistica. Our observations support the idea of a trauma induced Alzheimer–like degenerative process and indicate that such a condition is associated with a marked preponderance of ‘diffuse’ plaques.
Heat shock protein expression in corpora amylacea in the central nervous system: clues to their origin
Authors: MARTIN J. E. , MATHER K. , SWASH M. , GAROFALO O. , LEIGH P. N. , ANDERTON B. H.
Published: May 2008

Small bodies expressing epitopes of the 72 kD heat shock protein (HSP) have been identified in the brain and spinal cord in normal and neurologically abnormal individuals. These bodies resemble the ‘pre‐corpora amylacea’ (pre‐CA), thought to be the primary structure in the development of the mature body. Corpora amylacea are laminated hyaline bodies composed of polyglucosans. They are found in larger numbers with increasing age in the brain and spinal cord. Mature, histologically ‘classical’, corpora amylacea express epitopes of HSP chiefly at the periphery of the corpus, whilst smaller immature ‘pre‐corpora’ stain intensely throughout the entire structure. A heat shock or stress response in neurons and glial cells may be part of the cellular reaction to accumulation of abnormal products.
Propionic acidaemia: a neuropathological study of two patients presenting in infancy
Authors: HARDING B. N. , LEONARD J. V. , ERDOHAZI M.
Published: May 2008

The clinical and neuropathological findings are described in two children with propionic acidaemia presenting in infancy; they survived for 4 and 16 years respectively. Abnormalities were noted in the basal ganglia of both patients. In one child who clinically had severe athetosis, there was marbling of the corpus striatum. Clinical and morphological evidence suggests that the basal ganglia are especially vulnerable in propionic acidaemia.
Spindle‐cell glioblastoma or gliosarcoma?
Authors: JONES H. , STEART P. V. , WELLER R. O.
Published: May 2008

‘Gliosarcomas’ have long been considered to be mixed gliomas and sarcomas. The present study failed to define criteria which clearly delineate ‘gliosarcomas’ from glioblastoma multiforme and suggests that ‘gliosarcomas’ should be considered as spindle cell glioblastomas. A total of six cases originally diagnosed as ‘gliosarcomas’ were compared with four cases of glioblastoma multiforme. No clinical or prognostic features were defined which would clearly separate ‘gliosarcomas’ from glioblastoma multiforme. Macroscopically, biopsies from ‘gliosarcomas’ ranged from firm, apparently well‐circumscribed tumours to poorly circumscribed lesions with a soft consistency resembling glioblastoma multiforme. Histology revealed a continuous spectrum in which ‘gliosarcomas’ with large reticulin‐rich areas of spindle cells merged with typical glioblastomas containing only small islands of spindle cells and reticulin staining. Immunocytochemistry for glial fibrillary acidic protein (GFAP), S100 protein and α‐smooth muscle actin (ASM A) showed that the majority of cells in reticulin‐poor areas of ‘gliosarcoma’ and glioblastomas expressed S100 protein and GFAP; many expressed ASM A and some expressed both GFAP and ASMA. Spindle cells in reticulin‐rich areas of ‘gliosarcomas’ and glioblastomas most frequently expressed ASMA but many cells also expressed S100 protein and GFAP; some cells expressed both GFAP and ASMA. The results of this study and a review of the literature suggests that there is a clinical, radiological and pathological continuum with glioblastoma and ‘gliosarcoma’ at different ends of the spectrum. It is suggested, therefore, that most, if not all, ‘gliosarcomas’ be redesignated as spindle cell glioblastomas and not be considered as a mixture of glioma and sarcoma.
Widespread serum amyloid P immunoreactivity in cortical amyloid deposits and the neurofibrillary pathology of Alzheimer's disease and other degenerative disorders
Authors: KALARIA R. N. , GALLOWAY P. G. , PERRY G.
Published: May 2008

Amyloid P (AP) component is present in all types of systemic amyloid deposits. Recently, it has been shown to be also present in cerebral amyloid lesions of Alzheimer's disease (AD). In this study, we used immunocytochemical methods to extend these findings at the electron microscope level and characterize the spectrum of AP immunoreactivity in neurofibrillary pathology (NFP) of AD and other neurodegenerative disorders including Down's syndrome (DS), Creutzfeldt‐Jakob, Parkinson's, Pick's and diffuse Lewy body diseases and progressive supranuclear palsy. In AD and DS, AP immunoreaction product was evident in all the classical amyloid lesions and NFP in a large sample of all cortical areas examined. The distribution and relative intensity of immunostaining was similar to that of thioflavin S staining in serial sections. In many cases, however, plaques and vessels stained by anti‐AP serum were not apparent with thioflavin S. Serial sections immunostained with antiserum to amyloid A, C‐reactive protein or to other proteins involved in systemic amyloidoses and the acute phase response showed no evidence of staining in any of the cerebral lesions. Electron microscopy confirmed that AP immunoreactivity was associated with the abnormal filaments characteristic of NFP as well as amyloid fibrils found in plaques and vessels showing congophilic amyloid angiopathy. Plaques of Creutzfeldt‐Jakob disease, Pick bodies of Pick's disease, tangles and Lewy bodies in Parkinson's disease and a subpopulation of Lewy bodies in the diffuse Lewy body disease coexistent with AD were also stained. With the exception of vessels in two of the five cases, AP was not detected in age‐matched controls. Our observations indicate AP to be a consistent feature of cerebral NFP and amyloid deposits.
Neuronal hypertrophy in the pars reticulata of the substantia nigra in Parkinson's disease
Authors: NEAL J. W. , PEARSON R. C. A. , COLE G. , POWELL T. P. S.
Published: May 2008

The size of neurons in the pars reticulata of the substantia nigra in patients dying with Parkinson's disease has been compared with that in non‐parkinsonian control cases. Parkinson's disease is accompanied by a significant (4‐ 53%) hypertrophy of reticulata neurons. This is similar to changes seen in experimental rats with ipsilateral damage of the striatum. It is suggested that the enlargement seen in Parkinson's disease, similar to that in the rat, is indicative of plasticity in the GABA‐ergic reticulata neurons, and may be associated with increased inhibitory flux in pathways arising from the pars reticulata to the superior colliculus and thalamus.
Membrane flow within the myelin sheath in IDPN neuropathy
Authors: BLAUROCK A. E. , CLAIR M. B. GENTER ST , GRAHAM D. G.
Published: May 2008

This Report describes some aspects of P, p'‐iminodipropionitrile (IDPN) neuropathy in rats as observed by ultrastructural methods and X‐ray diffraction. Light microscopy shows gross swelling of the axons in proximal lumbar spinal roots 8 days after intraperitoneal injection of IDPN. Mean axon cross‐sectional area and mean axon perimeter increased to 280% and 160% of their control values, respectively. At the same time, myelin membrane packing was not visibly disturbed. In addition, X‐ray diffraction patterns, recorded under physiological conditions, demonstrate that the myelin lipid bilayer thickness and widths of the aqueous spaces between bilayers did not change. Related observations are made on posterior tibial nerve (PNS myelin) and ventral spinal cord (CNS myelin). The various observations together are interpreted in terms of a fluid myelin membrane. It is proposed that the myelin membrane flows during axon swelling even though normal membrane‐membrane contacts are maintained within the sheath. Membrane flow and slippage between membranes are explained in terms of a molecular model of the myelin multilayer.
Rumpshaker: an X‐linked mutation affecting CNS myelination. A study of the female heterozygote
Authors: FANARRAGA M. L. , GRIFFITHS I. R. , McCULLOCH M. C. , BARRIE J. A. , CATTANACH B. M. , BROPHY P. J. , KENNEDY P. G. E.
Published: May 2008

This study examines the myelin deficits found in the spinal cord and optic nerves of female mice heterozygotes for rumpshaker (rsh), an X‐linked mutation causing hypomyelination. No clinical abnormalities were detected but morphological changes were evident, particularly in the spinal cord, which showed no evidence of resolving with age. In the spinal cord, scattered hypomyelinated axons, occasionally grouped in twos or threes, were the major feature; oligodendrocyte numbers were slightly elevated at all ages compared to normal male littermates and the total amount of myelin was reduced. Myelin protein composition of the sheaths was examined by immunostaining for myelin basic protein (MBP) and two peptide regions of PLP/ DM‐20 molecule; one being proteolipid protein (PLP)‐specific and the other recognizing the c‐terminal common to PLP‐DM‐20. The majority of myelin sheaths immunostained for MBP and PLP. Occasional MBP‐positive sheaths failed to stain with PLP/DM‐20 or PLP‐specific antiserum. Therefore, at least two types of immunocytochemically‐defined myelin sheaths are present in the heterozygotes. Changes in the optic nerves were much less obvious; glial cell numbers were increased but thinly myelinated axons were not detected although the total amount of myelin was reduced compared to normal littermates. In no instance were mosaic, amyelinated/ hypomyelinated patches detected. Heterozygotes for rsh, therefore, are considerably different from those for other X‐linked myelin mutations like the jimpy mouse and the myelin‐deficient rat, both in regard to the severity of the lesions and their failure to recover with age.
Demonstration of β amyloid protein‐containing neurofibrillary tangles in parkinsonism‐dementia complex on Guam
Authors: ITO H. , HIRANO A. , YEN S. H. , KATO S.
Published: May 2008

This Report concerns the immunohistochemical demonstration of β amyloid protein‐containing neurofibrillary tangles (β‐NFTs) from patients with parkinsonism‐dementia complex on Guam (PDC). Formalin‐fixed paraffin‐embedded tissue sections from the temporal lobe of nine PDC cases and the spinal cord of three were examined. An affinity‐purified antibody to the N‐terminal peptide sequence of p amyloid protein was used. β‐NFTs were demonstrated in the temporal lobes of the three oldest individuals. Some senile plaques, probably a manifestation of ageing, were also seen. The β‐NFTs were most frequent in the entorhinal cortex. Senile plaques were invariably present in the vicinity of the β‐NFTs. Conversely, in the regions without senile plaques, even though numerous neurofibrillary tangles were identifiable with the modified Bielschowsky method, no β‐NFTs were seen. The density of β‐NFTs appeared to be proportional to that of senile plaques, none was seen in cases lacking senile plaques. No β‐NFTs were detected in the spinal cords. Our data suggest that β‐NFTs result from secondary P amyloid deposition on certain neurofibrillary tangles.
Developmental profile of plasma proteins in human fetal cerebrospinal fluid and blood
Authors: BELL J. E. , FRYER A. A. , COLLINS M. , MARSHALL T. , JONES P. W. , STRANGE R. , HUME R.
Published: May 2008

Total protein, alphafetoprotein, albumin, prealbumin, alpha‐1‐antitrypsin, transferrin and ceruloplasmin levels were measured in samples of human fetal and neonatal cerebrospinal fluid (CSF) (97 cases), obtained between 12 and 41 weeks of gestation. In 39 of these cases (13 to 40 weeks gestation) plasma was also available for comparative analysis. CSF was collected from lateral ventricles in the first half of gestation and from the lumbar region in the second. Since these CSF samples were obtained from different sites, the protein levels in the lateral ventricle (early) samples could not be compared directly with those in the lumbar (later) samples. However, the mean protein levels in the lumbar samples were lower than those in the ventricular samples, which is in accord with the decline in CSF protein levels described in maturing animal fetuses. Despite a wide scatter of results, particularly in the first half of gestation, significant decline in the level of CSF alphafetoprotein was demonstrated during both first and second halves of gestation, and of albumin and prealbumin in the second half. No sex differences were found except for ceruloplasmin in lumbar CSF later in gestation, when males had higher levels than females.

In fetal plasma, protein levels increased with increasing gestation apart from alphafetoprotein and prealbumin which both declined progressively. CSF/plasma ratios were dissimilar for different proteins, and changed with increasing gestation. These findings support the concept that the human fetal blood brain barrier matures early.
A primary demyelinating disorder of young cattle
Authors: PALMER A. C. , JACKSON P. G. G. , BLAKEMORE W. F.
Published: May 2008

The clinical signs and neuropathological changes are described in six Limousin X calves that, at about one month after birth, showed signs of blindness, nystagmus, rotation of the eyes, opisthotonos, hyperprotraction of the forelegs and, in one case, apparent seizures. Pathologically there was necrosis of the optic chiasma and focal areas of myelin sheath vacuolation or demyelination in certain areas of the brain, especially in the cerebellar peduncles. In one animal, kept alive for 7 months, there was remyelination by Schwann cells of some demyelinated axons in the focal cerebellar lesions, while other axons remained demyelinated. There was no evidence of oligodendrocyte remyelination. The cause of the condition was not determined but a genetic association is likely.
Heterotransplantation of a human oligoastrocytoma into nude mice: difference in tumour growth between males and females
Authors: VERZAT C. , COURRIERE P. , HOLLANDE E.
Published: May 2008

A human oligodendroglial tumour cell line was established in the nude mouse from a mixed oligoastrocytoma. This cell line was identified by immunoperoxidase screening for glial fibrillary acid protein (GFAP) and Leu‐7, by electron microscopy, by its growth behaviour, and by radioreceptor assays for oestrogen, progestogen and androgen. At the first heterotransplantation, the tumour grew in the female but not in the male mice. GFAP‐positive cells were much less abundant than in the initial tumour, although Leu‐7 positive cells were plentiful. Growth curves were biphasic, and the tumours contained both oestrogen and androgen receptors. After three successive hetero transplantations in female mice, GFAP‐negative, Leu‐7‐positive tumours with the cytological features of an oligodendroglioma were obtained. In contrast to those of the first heterotransplantation, the growth curves showed a longer latency and a single growth phase. The tumours contained both progestogen and androgen receptors but lacked oestrogen receptor. The 5th heterotransplantation in male mice exhibited rapid growth, similar to the three previous heterotransplantations in the female mice. The growth observed solely in the female mice at the first heterotransplantation was thought to derive from the hormonal status of the host. The presence of hormone receptors in the tumours at the first heterotranspiantation lent support to this idea. There was no further influence of the sex of the host on tumour growth once the oligodendroglial line was established. The establishment and the development of oligodendrocytes may result from differentiation of transitory cells intermediate between astrocytes and oligodendrocytes. The effect of host‐sex on the development of oligodendrocytes points to a new facet of the differentiation of CNS glial cells.
The induction of neural tube defects by maternal hyperthermia: a comparison of the guinea‐pig and human
Authors: SMITH M. S. R. , UPFOLD J. B. , EDWARDS M. J. , SHIOTA K. , CAWDELL‐SMITH J.
Published: May 2008

In our recent studies on the effects of maternal hyperthermia on the embryonic guinea‐pig, we have demonstrated two ‘teratogenic windows’ at embryonic days 13 and 21 (E13 and E21). E13 encompasses the period of the closure of the neural groove and anterior neuropore, and E21 the commencement of the cortical plate. The approximate equivalent developmental times in the human are E23‐E25 and E49‐E56 respectively. In the guinea‐pig, maternal hyperthermia at E13 results in a high incidence of neural tube defects (NTD), many open, and associated with other defects such as microphthalmia, and scoliosis or kyphosis. The NTD were most common in the developing hindbrain and all demonstrated considerable infoldings of neural tissue, rosettes of neuroepithelial cells, outpocketings of neural tissue and large cystic cavities beneath the defect. In human examples from the Kyoto Human Embryo Collection, 16 had verified hyperthermic insults at E23‐E25 and all had NTD which showed similar deformities to the guinea‐pig. Most embryos with such gross defects are aborted in the early fetal period in both species.
Pathological study of corticospinal‐tract degeneration in Friedreich's ataxia
Authors: MURAYAMA S. , BOULDIN T. W. , SUZUKI K.
Published: May 2008

The pattern of fibre degeneration in the lateral corticospinal tract (LCST) was studied in a case of Friedreich's ataxia (FA). There was preferential involvement of the lateral area of the LCST in the cervical spinal cord. More caudally, the degeneration involved the entire area of the LCST and did not reveal a medial to lateral gradient of involvement. We suggest that this distinctive pattern of tract degeneration is a consequence of the somatotopic organization of the LCST, with the dying‐back degeneration preferentially affecting those LCST fibres that extend to the lumbo‐sacral spinal cord. This pattern of tract degeneration may be a useful morphological marker of dying‐back degeneration in corticospinal tracts.
The polymerase chain reaction and its applications in neuropathology
Authors: LOVE S. , NICOLL J. A. R.
Published: May 2008

The polymerase chain reaction (PCR) provides a means of generating large numbers of copies of selected segments of DNA. Once amplified, the DNA can be characterized by determination of its size and sequence. For many applications, routinely‐processed biopsy and autopsy material is an adequate substrate for the reaction. PCR can be used to amplify sequences of DNA that are uniquely characteristic of particular micro‐organisms, allowing their rapid detection in samples of tissue or cerebrospinal fluid. The technique allows clones of cells with gene rearrangements or translocations to be detected with great sensitivity and is proving a useful way to monitor the effects of tumour therapy, particularly in patients with lymphomas and leukaemias. Further applications include the identification of gene deletions and mutations, and the assessment of cell lineage by amplification and analysis of highly polymorphic gene loci (DNA fingerprinting). Because the degree of amplification resulting from PCR is so great, even a single molecule of contaminating DNA may be detected and its significance misinterpreted. Great care, therefore, should be taken to prevent contamination of samples, particularly by the products of previous reactions, and every series of reactions should include appropriate controls.
Quantifying the pattern of β/A4 amyloid protein distribution in Alzheimer's disease by image analysis
Authors: BRUCE C. V. , CLINTON J. , GENTLEMAN S. M. , ROBERTS G. W. , ROYSTON M. C.
Published: May 2008

We have undertaken a study of the distribution of the β/A4 amyloid deposited in the cerebral cortex in Alzheimer's disease. Previous studies which have examined the differential distribution of amyloid in the cortex in order to determine the laminar pattern of cortical pathology have not proved to be conclusive. We have developed an alternative method for the solution of this problem. It involves the immunostaining of sections followed by computer‐enhanced image analysis. A mathematical model is then used to describe both the amount and the pattern of amyloid across the cortex. This method is both accurate and reliable and also removes many of the problems concerning inter and intra‐rater variability in measurement. This method will provide the basis for further quantitative studies on the differential distribution of amyloid in Alzheimer's disease and other cases of dementia where cerebral amyloidosis occurs.
Ultraviolet irradiation induced brain oedema in rats. A microgravimetric study
Authors: LAFUENTE J. V. , CRUZ‐SANCHEZ F. F. , ROSSI M. L. , CERVOS‐NAVARRO J.
Published: May 2008

The cerebral cortex of 36 anaesthetized Wistar rats were exposed to ultraviolet irradiation (UV‐I) for 6 min through a 2 × 2 mm left parietal craniotomy. Animals were killed at different times and brains were removed immediately after death. Three consecutive coronal sections were obtained and sampled for gravimetric study. The density of the samples was measured using a continuous gradient of organic solvents. Gravimetric results showed significant differences between brain samples. The irradiated left hemisphere was less dense than the right one, and maximum differences in density were found in the medial coronal section. Grey and white matter oedema in the non‐irradiated hemisphere was compared with the irradiated hemisphere. Early and delayed onset of oedema was observed in both hemispheres but it was more marked in the irradiated hemisphere. In conclusion, brain oedema induced by ultraviolet irradiation in various animals is also reproducible in rats with all the advantages involved in the use of these experimental animals. Microgravimetric study correlated with topographical analysis using this model may lead to an understanding of some of the dynamic aspects of cerebral oedema.
The pathological evolution of multiple sclerosis
Authors: McDonald W. I. , MILLER D. H. , Barnes D.
Published: May 2008

The new technique of nuclear magnetic resonance imaging (NMR) has been found to have particular value in the study of the evolution of the plaque of multiple sclerosis. Particularly when combined with gadolinium enhancement, the method not only shows very dramatically the waxing and waning of the plaque with time, it also demonstrates with remarkable clarity the important role of changes in vascular permeability in the pathological process. In this Annotation the ability of this technique to throw new light on the process of plaque formation and evaluation is critically assessed. In addition, the role of changing fluid content of the extra cellular spaces of the CNS in influencing interpretation of the more conventional clinical and electrophysiological findings is discussed. While the method of NMR analysis does not yet show us how the plaque is initiated, it is suggested that future studies with these new techniques in the living subject may well lead us to rational therapeutic approaches based on pathogen tic mechanisms.
Subependymal cells provide a faster response to ependymal injury than astrocytes in the hydrocephalic brain
Authors: COLLINS P. , GOULDING D. A.
Published: May 2008

Obstructive hydrocephalus was induced in 12‐day‐old rats by the infusion of kaolin into the cisterna magna. After 7 days, cortical and ependymal lesions were made with thin wire in non‐hydrocephalic brains and in hydrocephalic brains. The wounds were allowed to heal for times ranging from 1 day to 10 days post‐lesion, after which the animals were perfused and the brains prepared for histology. Paraffin sections of brain containing the ependymal wound were reacted for glial fibrillary acidic protein by the avidin biotin complex technique. Subependymal cells were associated with the ependymal defect from 1 day in both non‐hydrocephalic and in hydrocephalic brains. Reactive astrocytes were identified in hydrocephalic wounded brains on day 3. It was not until day 6 that astrocytes and astrocytic processes were seen in association with the subependymal cells at the wound edge, and astrocytic processes were noted along the needle track in the cortex. The results suggest that the extremely rapid response of subependymal cells to ependymal injury is a mechanism distinct from the astrocytes response for repair in the brain.
Astrocyte‐endothelial interaction: physiology and pathology
Authors: ABBOTT N. J. , REVEST P. A. , ROMERO I. A.
Published: May 2008

The blood‐brain barrier of higher vertebrates is formed by the layer of endothelial cells lining the brain microvessels. The close anatomical association between endothelial cells and per vascular astrocytic end feet suggests cooperation between these cell types in forming and maintaining the blood‐brain barrier. This review considers evidence from grafting experiments, developmental studies and culture models of the brain endothelium, concerning the inductive influences acting on the endothelium, and from endothelial cells acting on perivascular astrocytes. Examples from pathology and neurotoxicology which may involve breakdown of induction are also considered.
Transplanted cultured type‐1 astrocytes can be used to reconstitute the glia limitans of the CNS: the structure which prevents Schwann cells from myelinating CNS axons
Authors: BLAKEMORE W. F.
Published: May 2008

Transplantation of different glial cells into areas of demyelination made in the adult rat spinal cord allows insights into the cell‐cell interaction necessary to reconstruct a glial environment around demyelinated axons. Such studies have shown that type‐1 astrocytes are central to the exclusion of Schwann cells from areas of glia‐free demyelination. However, for these cells to be established in a manner which prevents Schwann cell remyelination of CNS axons, cells of the 0–2A lineage are also required. If cultures of isogeneic rat type‐1 astrocytes and mouse O‐2A cells are transplanted into lesions made in non‐immunosuppressed animals, Schwann cell remyelination is limited and extensive oligodendrocyte remyelination is achieved. This paradigm creates a model of immune mediated demyelination in which the immune response is not primarily directed at oligodendrocyte specific epitopes.
Varicella‐zoster virus encephalitis in acquired immunodeficiency syndrome: Report of four cases
Authors: GRAY F. , MOHR M. , ROZENBERG F. , BELEC L. , LESCS M. C. , DOURNON E. , SINCLAIR E. , SCARAVILLI F.
Published: May 2008

Four patients with acquired immunodeficiency syndrome, a 27‐year‐old female intravenous drug abuser and three males (two drug addicts aged 27 and 33 years and a 40‐year‐old homosexual) presented with a rapidly progressive encephalopathy. Two had generalized varicella‐zoster virus skin infection, one had had a regressive thoracic zoster rash 7 months previously and one had no history of cutaneous eruption. Neuropathological examination revealed, in each case, multifocal necrotic changes with numerous, intranuclear Cowdry type A inclusion bodies in glial cells, endothelial cells, macrophages and neurons, within and around the lesions. These inclusion bodies were stained positively for varicella‐zoster virus by immunocytochemistry and contained herpes virus nucleocapsids by electron microscopy. Molecular biology using the polymerase‐chain‐reaction method demonstrated viral genome. In one case, zoster‐induced non‐inflammatory vasculopathy involved medium sized lepto‐meningeal vessels and was associated with circumscribed areas of cortico‐subcortical infarction. In another case, varicella‐zoster virus encephalitis was associated with human immunodeficiency virus encephalitis and a secondary cerebral lymphoma. Multinucleated giant cells expressing human immunodeficiency virus proteins in their cytoplasm, were found in the lymphomatous deposits and in the varicella‐zoster virus necrotic lesions. In these latter lesions, Cowdry type A inclusion bodies could be seen in the nuclei of some multi‐nucleated giant cells confirming previous observations of MGCs co‐infected by HN and CMV, and supporting the hypothesis that DNA viruses interact with HN, thus increasing its effect.
Progressive degeneration of motor nerve terminals in GAD mutant mouse with hereditary sensory axonopathy
Authors: Miura H. , Oda K. , Endo C. , Yamazaki K. , Shibasaki H. , Kikuchi T.
Published: May 2008

The evolution of motor nerve degeneration was examined in gracile axonal dystrophy (GAD) mutant mice, which develop initial sensory ataxia and subsequent motor paresis. Using the anterior gracilis (AG) muscle, which is innervated at two discrete and well‐separated end‐plate zones, we demonstrated that axonal degeneration occurred first at motor nerve terminals in the distal end‐plate zone, and then extended gradually from the distal to the more proximal parts of affected axons in the intramuscular nerve trunk. In contrast to the degeneration in the distal zone, active degeneration was less marked in the proximal endplate zone and, furthermore, most terminal axons had begun to produce regenerating sprouts. Ventral horn cells were histologically normal, even at advanced stages. These results indicate that, as previously observed in sensory nerves, dying back degeneration progresses later in the lower motor neuron system, even within one muscle. The mechanism(s) influencing the activation of axonal regeneration are discussed. This mutant mouse will be a useful model for the study of regenerating phenomena in dying back degeneration of genetically compromised motor neurons, as well as for the study of the pathogenesis of hereditary sensory and motor neuropathies in man.
Neurocytoma/lipoma (neurolipocytoma) of the cerebellum
Authors: Ellison D. W. , Zygmunt S. C. , Weller R. O.
Published: May 2008

We describe a unique tumour that was removed from the posterior fossa of a woman aged 50 years. It was characterized histologically by bland, oval cells with fibrillary cytoplasm and by small groups of lipocytes. Immunocytochemical studies demonstrated expression of synaptophysin, neuron specific enolase and PGP 9.5, but a few cells also expressed glial fibrillary acidic protein and desmin. The combination of neuroectodermal and mesodermal features in this tumour is discussed in relation to primitive neuroectodermal tumours and neurocytoma
Secretion of cathepsin B by human gliomas in vitro
Authors: McCormick D.
Published: May 2008

There is evidence from investigations of non‐CNS neoplasms that secreted proteolytic enzymes may facilitate tumour invasion by partially degrading extracellular matrix (ECM). Among the enzymes which may be involved are members of the cysteine proteinase superfamily and especially cathepsin B (CB). In the present investigation we have studied CB in human gliomas in vitro, concentrating particularly on CB secretion, as extracellular enzyme is of prime importance in this context. We have found that CB is secreted by gliomas in vitro as a latent zymogen, requiring activation. This has been confirmed by gel chromatography which indicated that CB is secreted as a 42 kDa proenzyme which may be proteolytically processed to an enzymatically active 29 kDa molecule. The inactive, high molecular weight, latent CB is stable at extracellular pH in contrast to the activated low molecular weight form which rapidly loses activity at this pH. We have also measured secretion of cysteine proteinase inhibitors (CPI), as their presence would have a direct influence on the effective activity of CB, and found that all of the gliomas secreted significant amounts of a CPI as assessed by papain inhibition. Our experiments suggest that a number of factors are involved in the regulation of extracellular glioma‐derived CB activity. These include: rate of secretion of pro‐CB, rate of CB activation, destabilization of CB at neutral pH and the presence of cysteine proteinase inhibitors.
Proliferating cell nuclear antigen (PCNA): expression in samples of human astrocytic gliomas
Authors: Revesz T. , Alsanjari N. , Darling J. L. , Scaravilli F. , Lane D. P. , Thomas D. G. T.
Published: May 2008

In this retrospective study, 55 astrocytic tumours were stained with monoclonal antibody PC10 which recognizes the proliferating cell nuclear antigen (PCNA) in formalin fixed, paraffin‐wax embedded sections. All the cases were graded using the Daumas‐Duport system and the PCNA labelling indices (LIs) were correlated with tumour grades. Mean PCNA LI was 4.1% in the grade II, 8.1 % in the grade III and 26.1% in the grade IV group. Six juvenile and cerebellar (grade I) astrocytomas had a mean PCNA LI of 5.6%. In general PCNA LI increased with tumour grade, but there was considerable variation of LIs especially in grade IV tumours which often had very high PCNA LIs (up to 72.7%). PC10 may be a useful complementary technique in surgical neuropathology, but the significance of the high LIs, seen in a proportion of glioblastomas, needs to be further determined.
Failure of remyelination in areas of demyelination produced in the spinal cord of old rats
Authors: Gilson J. , Blakemore W. F.
Published: May 2008

The extent of remyelination was determined one month after injecting 1μl of 1.0% lysolecithin into the dorsal columns of adult rats of three age groups—juvenile, young and old. In the juvenile group (2 months) all axons were remyelinated by either oligodendrocytes or Schwann cells. In the young rats (5 months) nearly all axons were remyelinated. However, in the oldest age group (> 12 months) many axons remained demyelinated and there was a decrease in both oligodendrocyte and Schwann cell remyelination. Also, myelin sheaths formed by oligodendrocytes in the old rats were thinner than those found in the young rats; evidence of impaired Schwann cell remyelination was also seen. The appearance of the lesions in the old animals was variable and many contained myelin debris despite the presence of macrophages within the demyelination area. Although some astrocytes were present in the lesion, many of the demyelinated axons were not separated by astrocyte processes. It is suggested that the failure of remyelination in the old rats following lysolecithin‐induced demyelination may be related to sluggish responses of astrocytes and/or macrophages to demyelination. However, a lack of recruitable myelin‐forming cells in old animals cannot be excluded.
The neurotoxicity of α‐chlorohydrin in rats and mice: I. Evolution of the cellular changes
Authors: Cavanagh J. B. , Nolan C. C. , Seville M. P.
Published: May 2008

Mice and rats are found to be equally susceptible to developing symmetrical brain stem lesions on exposure to α‐chlorohydrin and in both species the earliest neurotoxic changes are strictly confined to glial cells, particularly astrocytes; haemorrhages are not found in either species. Minimal evidence of increased vascular leakage of horseradish peroxidase (HRP) in rats is shown by increased HRP content of perivascular cells within the lesions. Later macrophage invasion and capillary proliferation is accompanied by rare focal leakiness of HRP. Gross astrocytic damage, therefore, does not necessarily impair integrity of the blood‐brain barrier. While early in intoxication, astrocytes are severely distended with fluid and their organelles seriously disorganized, they do not die but rapidly regenerate their processes. They thus appear to undergo a process of ‘clasmatodendrosis’ from which they recover. Comparisons are made with the genesis of symmetrical brain stem lesions in other acute energy deprivation syndromes, including Wernicke's encephalopathy.
Astroglial changes in the cerebral cortex of AIDS brains: a morphometric and immunohistochemical investigation
Authors: Weis S. , Haug H. , Budkat H.
Published: May 2008

Astroglial changes in the cerebral cortex of AIDS brains were analysed by means of morphometry. Astrocytes with and without immunoreactivity for glial acidic protein (GFAP) were counted and their size was measured. In the two investigated cortical areas (frontal and parietal), a similar reaction pattern of astroglia was observed. The total number of astrocytes (i.e. GFAP‐positive and GFAP‐negative astrocytes) did not differ between control and AIDS brains. However, the number of GFAP‐positive astrocytes was significantly increased in AIDS brains, while the number of GFAP‐negative cells was significantly reduced. Nuclear size of GFAP‐negative and GFAP‐positive astrocytes was significantly increased. The reaction pattern of cortical astrocytes in AIDS seems to be characterized by GFAP production in protoplasmic astroglia as well as by hypertrophy of all astrocytes.
Different patterns of neuropathological disease in rhesus monkeys infected by simian immunodeficiency virus, and their relation to the humoral immune response
Authors: Dean A. F. , Montgomery M. , Baskerville A. , Cook R. W. , Cranage M. P. , Sharpe S. A. , Dennis M. J. , Luthert P. J. , Hou S‐T. , Lantos P. L.
Published: May 2008

The brains of 21 rhesus monkeys inoculated with SIVMAC51 were examined after intervals ranging from 3 to 27 months and compared with five uninoculated controls. Eighteen animals became infected and individually exhibited several distinct patterns of disease. Nine (50%) had largely intramural leptomeningeal venous infiltrates (LMVI) without multinucleate giant cells (MGC) or foamy macrophages. Three (17%) had only MGC lesions, involving the cerebral parenchyma. One had both patterns and five (33%) neither. The controls had sparse and tiny LMVI only, similar to three inoculated animals that did not become infected. Immunohistochemistry showed the predominance of T and B lymphocytes in LMVI and choroid plexus mononuclear lesions but a predominance of macrophages over lymphocytes in the MGC lesions. Specific disease patterns differed in their association with the humoral immune response. Animals with LMVI were all hypergammaglobulinaemic when killed compared to pre‐inoculation levels, and the size of the change in serum immunoglobulin concentration was positively correlated with a quantitative index of LMVI density. Furthermore, their post‐mortem lymph node histology was hyperplastic. In contrast, animals found at autopsy to have MGC brain lesions were hypogammaglobulinaemic compared to pre‐inoculation. The results are consistent with two phases in SIV‐associated disease: one characterized by LMVI and hypergammaglobulinaemia and another featuring MGC and hypogammaglobulinaemia.
Fusion of myogenic cells to the newly sealed region of damaged myofibres in skeletal muscle regeneration
Authors: Robertson T. A. , Papadimitriou J. M. , Grounds M. D.
Published: May 2008

In regenerating skeletal muscle, sarcoplasmic extensions containing variable numbers of nuclei, widely referred to as ‘buds’ or ‘stumps’, are formed at the ends of damaged myofibres. In this paper we investigated whether the nuclei seen in the buds results from fusion of myogenic cells or from migration of myonuclei to the sealed ends of damaged myofibres in murine muscle regenerating after crush injury. The fusion of mononuclear and multinucleate myogenic cells to the buds was demonstrated by transmission electron microscopy. In order to elucidate the frequency and kinetics of cytoplasmic continuity between myotubes and sealed myofibres, we labelled the damaged myofibres with carbocyanine dye DiI (which inserts into the lipid bilayer and travels down continuous membranes) and the samples were then examined by con‐focal scanning microscopy. This technique showed that there was little fusion between myotubes and myofibres during the first 6 days after crush injury, but significant fusion had occurred by the tenth day especially at the newly sealed region of the damaged myofibre. A scheme for the repair of damaged skeletal muscle is presented.
Leucotomized schizophrenics lose neurons in the mediodorsal thalamic nucleus
Authors: Pakkenberg B.
Published: May 2008

It has previously been shown that chronic schizophrenic patients have a 40–50% reduction in the total number of nerve and glia cells in the mediodorsal thalamic nucleus and the nucleus accumbens compared with controls, while the total neuron and glia number is the same in the two groups in the ventral pallidum. Using new stereological cell counting methods, neuron and glia cell numbers were estimated in the mediodorsal thalamic nucleus, the ventro‐medial part of nucleus accumbens and the ventral pallidum in nine brains from leucotomized schizophrenics. This number was compared with counts from control cases and chronic schizophrenics without leucotomy. The results showed that the total number of nerve cells in the mediodorsal thalamic nucleus was statistically significantly reduced from 1.08 × 106 in chronic schizophrenics to 0.88 × 106 in leucotomized schizophrenics. Total neuron number was statistically significantly reduced in the ventro‐medial part of the nucleus accumbens in schizophrenics without further reduction in leucotomized schizophrenics. The total neuron number in ventral pallidum was normal. With frontal leucotomy it is possible to investigate the consequences of disconnection of the prefrontal cortex to central regions in the human brain. The mediodorsal nucleus of thalamus represents a major efferent projection to the prefrontal cortex. The dorsal prefrontal cortex projects to nucleus caudatus and the orbital prefrontal cortex to the nucleus accumbens, a prominent region in the limbic system. It was expected that a lesion to the prefrontal region by anterograde, retrograde degeneration may affect the mediodorsal nucleus of thalamus.
Selective excitotoxic pathology in the rat hippocampus
Authors: Jarrard L E. , Meldrum B. S.
Published: May 2008

The pattern of cell loss and neuronal degeneration resulting from multiple microinjections of N‐methyl‐D‐aspartate (NMDA), ibotenate (IBO), quisqualate (QUIS), and kainate (KA) into hippocampus was studied, together with the protection provided by the NMDA antagonist 3‐(±)‐2‐carboxypiperazin‐4‐yl‐propyl‐l‐phosphonate (CPP). Histological evaluation was carried out after 7 days of survival. NMDA and IBO resulted in an extensive loss of all cells in the hippocampus including dentate gyrus, hilar cells, and CA3‐CA1 pyramidal cells, but there was an absence of damage to areas and structures outside hippocampus. After QUIS and KA injections the hippocampal damage was limited to hilar cells in the dentate gyrus, CA3 pyramidal cells, and partial loss of CA1 cells; there was extensive extrahippocampal damage including entorhinal cortex, amygdala, layers III, V, and VI of ventral neocortex, olfactory areas, and various thalamic nuclei. CPP provided almost complete protection from the effects of intrahippocampal injections of NMDA and IBO, but did not affect the hippocampal cell loss found after QUIS and KA (with the exception of minor protection of some CA1 cells). CPP protected most extrahippocampal sites from the damage resulting from QUIS and KA, indicating that such excitotoxic cell death is indirect and involves NMDA receptor activation by an endogenous agent. The use of multiple microinjections as opposed to single injections allows a clearer interpretation of selective excitotoxic vulnerability.
Mumps virus alters aggregation of acetylcholine receptors in cultured rat skeletal muscle cells
Authors: Keli S. , Norrby E. , Kristensson K.
Published: May 2008

Cultured myoblasts, but not myotubes, from rat skeletal muscles were infected with the RW strain of mumps virus. Such myoblasts then fused to form myotubes containing viral antigen. The infected myotubes showed a significant decrease in the number of dorsal, linear acetylcholine receptor (AChR) aggregates as determined by FITC‐conjugated alfa‐bungarotoxin. Infected myotubes co‐cultivated with spinal cord cells showed no increase in the number of dorsal, linear AChR aggregates, compared to normal, uninfected myotubes. In addition, an increased proliferation of the myoblasts, which remained uninfected in the infected cultures, was noted. This may indicate a release of a growth stimulating factor from the virus containing cells. This study shows that mumps virus infection can lead to an altered receptor organization in a morphologically preserved cell.
Assessment of nuclear size, nuclear DNA content and proliferation index in stereotaxic biopsies from brain tumours
Authors: Salmon I. , Levivier M. , Camby I. , Rombaut K. , Gras T. , Pasteels J.‐L. , Brotchi J. , Kiss R.
Published: May 2008

In this paper we study the feasibility of measuring the diverse biological parameters in stereotaxic biopsies from human brain lesions. These biological parameters are the nuclear area (NA), the proliferation index (PI) and the ploidy level, the latter of which was evaluated by means of the DNA index (DI) and histogram type (DHT). These parameters were assessed by means of the digital cell image analysis of Feulgen‐stained nuclei. This analysis was performed on 124 samples from 22 computed tomography (CT)‐guided stereotaxic biopsies. The data show that the methodology used here enables the above parameters to be assessed on small samples without limiting the classical anatomopathological diagnosis. The data also reveal that the DHT corresponded more accurately to the ploidy level in the sample analysed than the DI. Lastly, it appears that supratentorial astrocytic tumours of the adult, which constituted the majority of the cases analysed here, are strongly heterogeneous at a biological level.
Hirano bodies and related neuronal inclusions
Authors: Hirano A.
Published: May 2008

Hirano bodies are bright eosinophilic intracytoplasmic inclusions which have a highly characteristic crystalloid fine structure. They occur preferentially in the neuronal processes of the CA1 area in Amnion's horn in a wide variety of conditions, especially amyotrophic lateral sclerosis and parkinsonism–dementia complex on Guam, Alzheimer's disease, Pick's disease and ‘normal’ elderly individuals. Hirano bodies contain epitopes of actin, actin–associated proteins, tau, middle molecular weight neurofilaments subunit and a C–terminal fragment of β‐amyloid precursor protein. In addition to the CA1 area of Amnion's horn, they have also been identified in many other areas of the nervous system in humans and various experimental animals. Although usually observed in neurons. Hirano bodies may also be present in other cell types. It is the consensus that Hirano bodies in the pyramidal layer of CA1 originate largely from an age‐related alteration of the microfilamentous system.