bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMMUNOSTAINING OF SCRAPIE CEREBRAL AMYLOID PLAQUES WITH ANTISERA RAISED TO SCRAPIE–ASSOCIATED FIBRILS (SAF)
Authors: McBRIDE P. A. , BRUCE M. E. , FRASER H. 
Published: May 2008

Immunostaining of scrapie cerebral amyloid plaques with antisera raised to scrapie–associated fibrils (SAF)Brain sections from 16 different mouse scrapie models were immunostained with antisera to scrapie–associated fibrils (SAF) from three experimental scrapie sources (hamster 263K, mouse ME7 and mouse 22L). These models involved seven strains of scrapie injected intracerebrally or intraperitoneally into a range of inbred mouse strains, producing a wide variety of neuropathological changes. The only brain structures which were positively immunostained were amyloid plaque cores in those models in which plaques could be readily identified using traditional amyloid stains. The intensity of immunostaining correlated with the density of amyloid in the cores, as detected by Congo red and thiofiavine S staining. No differences in immunostaining specificity were found between antisera or between plaques in different combinations of scrapie strain and mouse genotype. There were also no differences in immunoreactivity between plaques in different parts of the brain. These results strongly suggest that SAF and histologically detectable amyloid in scrapie mice are derived from the same precursor protein. Scrapie–associated cerebrovascular amyloid and plaques in sheep and goats also gave positive immunostaining with SAF antisera, although the lesions in the natural disease could only be stained after formic acid pretreatment. Senile plaques in Alzheimer's disease and Down's syndrome, although structurally similar to scrapie amyloid plaques, were found to be completely negative for SAF, in agreement with previous biochemical and immunocytochemical findings.
NECROTIZING VASCULITIS OF THE NERVOUS SYSTEM IN A PATIENT WITH AIDS–RELATED COMPLEX
Authors: VINTERS H. V. , GUERRA W. F. , EPPOLITO L. , III P. E. KEITH 
Published: May 2008

Necrotizing vasculitis of the nervous system in a patient with AIDS‐related complexA patient with AIDS‐related complex (ARC) presented with a fulminant neurologic syndrome suggestive of ascending myelopathy, and died approximately 48 h after admission to hospital. At necropsy, there was evidence of a severe necrotizing vasculitis affecting the nervous system most severely, with multifocal haemorrhagic necroses of the spinal cord and cauda equina. Although a rare intranuclear inclusion suggestive of herpesvirus infection was seen in the predominantly lympho‐histiocytic infiltrate in and around blood vessel walls, the precise aetiology of the angiitis was not apparent. It may represent a response to AIDS virus infection of one or more components of the blood vessel wall.
STRUCTURAL CHANGES IN THE RAT BRAIN AFTER CAROTID INFUSIONS OF HYPEROSMOLAR SOLUTIONS: A LIGHT MICROSCOPIC AND IMMUNOHISTOCHEMICAL STUDY
Authors: SALAHUDDIN T. S. , JOHANSSON B. B. , KALIMO H. , OLSSON Y. 
Published: May 2008

Salahuddin T. S., Johansson B. B., Kalimo H. & Olsson Y. (1988)Neuropathology and Applied Neurobiology14, 467–482Structural changes in the rat brain after carotid infusions of hyperosmolar solutions: a light microscopic immunohistochemical studyA solution of mannitol or urea was infused into the carotid artery of rats to open the blood–brain barrier (BBB) and to find out if such a procedure results in brain injury. Paraformaldehyde–fixed, paraffin–embedded material was available to determine the localization and extent of albumin extravasation by immunochemistry. Other light microscopic and immunocytochemical techniques were applied on consecutive sections to find out if structural damage had occurred.The cerebral cortex, the hippocampus and the basal ganglia of the infused brain hemisphere contained within regions of albumin extravasation scattered, collapsed, acidophilic neurons. In addition, there were multifocal lesions with marked sponginess of the neuropil which contained numerous shrunken, acidophilic neurons and a perifocal astrocytic gliosis. A moderate macrophage infiltration was present in rats with 72 h survival.In conclusion, infusion of hypertonic mannitol or urea into the carotid artery of the rat may result in structural brain damage within regions showing BBB injury. The presence of acidophilic neurons and the macrophage response indicate that some of the brain changes are irreversible.
THE SIGNIFICANCE OF THE LEWY BODY IN THE DIAGNOSIS OF IDIOPATHIC PARKINSON'S DISEASE
Authors: GIBB W. R. G. , LEES A. J. 
Published: May 2008

The significance of the Lewy body in the diagnosis of idiopathic Parkinson's diseaseA retrospective study of 269 patients with a clinical diagnosis of Parkinson's syndrome was carried out. Seventy‐eight were selected as cases of Parkinson's disease on the basis of generally accepted criteria. Of these, 73 were found to have Lewy bodies and cell loss in the substantia nigra, two had the pathological changes of striatonigral degeneration, two had extensive neurofibrillary tangles and nigral cell loss compatible with post‐encephalitic parkinsonian syndrome, and one had Lewy bodies and striatonigral degeneration. Pathological examination of the remaining brains revealed Lewy bodies with cell loss in the nigra, a different pathological diagnosis, or normal basal ganglia. No unclassifiable ‘senile’ patients, or cases with neurofibrillary tangle degeneration or extranigral pathology of unknown cause were found. As a result of these findings clinico‐pathological diagnostic criteria for Parkinson's disease are proposed. All patients with this diagnosis had Lewy bodies in surviving neurons of two unilateral 7 &#x006d;̈mi sections of the mid‐part of the substantia nigra. The frequency of Lewy bodies in multiple system atrophy, Steele‐Richardson‐Olszewski syndrome and Alzheimer's disease was low and similar to that in age‐matched ‘normal’ controls. Pathological findings were compatible with the notion that these individuals have preclinical or coincidental Parkinson's disease.
COMPARISON OF SEVEN STAINING METHODS FOR SENILE PLAQUES AND NEUROFIBRILLARY TANGLES IN A PROSPECTIVE SERIES OF 15 ELDERLY PATIENTS
Authors: LAMY C. , DUYCKAERTS C. , DELAERE P. , PAYAN CH. , FERMANIAN J. , POULAIN V. , HAUW J. J. 
Published: May 2008

Samples of brain from 15 prospectively tested women over 75 years of age, living in the same institution and with a Blessed test score between 0 and 28 were studied to evaluate seven different staining techniques for counting senile plaques and neurofibrillary tangles. The methods included Bielschowsky (modified by Yamamoto & Hirano, 1986), Cross, Gallyas, Naoumenko–Feigin, silver methenamine, Bodian coupled with luxol fast blue, and thioflavine S; these techniques were performed on contiguous slides of the first temporal gyrus (Brodmann's area 22). The cost, difficulty and variability of the methods were evaluated. Modified Bielschowsky method revealed both amyloid and neurites. Cross, Bodian and Gallyas stained neurites preferentially and were more sensitive for neurofibrillary tangles than for senile plaques. Silver methenamine revealed amyloid in much the same way as thioflavine S. The highest count of senile plaques and neurofibrillary tangles was obtained with the modified Bielschowsky method. Best correlations between density of senile plaques and Blessed test score were obtained with modified Bielschowsky impregnation, silver methenamine, and Bodian and those for neurofibrillary tangles, with modified Bielschowsky, Naoumenko–Feigin, and Gallyas methods. Naoumenko–Feigin impregnation, even if fitted to the linear model, revealed very few changes (four times less than modified Bielschowsky) and appeared to be insensitive. All the techniques except Naoumenko–Feigin, were equally able to distinguish two groups of cases, i.e. those affected by Alzheimer's disease and those not affected. A multiple regression analysis indicated that the statistical relationship between the density of changes, evaluated after the modified Bielschowsky method, and the Blessed test score could not be improved by the additional use of other staining techniques.These data have direct implications for the evaluation of diagnostic criteria in Alzheimer's dementia. In this study, modified Bielschowsky impregnation was found to give the most complete picture of the lesions and, as such, could be considered a reference method. This technique is, however, expensive and difficult to perform. It stains a large number of normal structures and the recognition of the lesions is more subjective than with other selective stains. It is therefore difficult to recommend this technique for routine use. Other techniques alone, or in combination, can be recommended but the diagnostic criteria should be adapted for each of them.
Notes from the graveyard: neuropathology and schizophrenia*
Authors: ROBERTS G. W. , BRUTON C. J. 
Published: May 2008

Schizophrenia is commonly regarded as a ‘functional’ psychosis, the implication being that the delusions, hallucinations and cognitive impairment characteristic of the disease have no organic basis. This view is due in no small way to the failure of pathologists to find convincing pathological changes associated with the disease in the first seven decades of the century. Over the last 10 years things have changed considerably. Recent CT and MRI scan studies have provided convincing evidence of significant ventricular enlargement in the brains of schizophrenics and post‐mortem studies have shown that schizophrenic brains are about 6% lighter than controls and have a reduced volume and reduced antero‐posterior length.Planimetric studies on post‐mortem material and a recent MRI study show that medial temporal lobe structures (parahippocampal gyrus, hippocampus and amygdala) are preferentially affected. Although other brain regions (e.g. cingulate gyrus, frontal cortex) also show alterations they appear to be ‘downstream’ from the regions primarily affected. Morphological studies show that there is a loss of neurons from medial temporal lobe structures and indicate irregularities in their cytoarchitectonic arrangement. The alterations in structure are not associated with degenerative, inflammatory, or abnormal vascular processes. There has been much debate as to the possible causes of the structural changes and whether they are limited to particular ‘types’ or sub‐groups of schizophrenics. At present it seems simpler to suppose that all schizophrenics have a degree of structural abnormality which may differ in degree but not in kind.It has been proposed that the changes in brain structure in schizophrenia are the result of an anomaly of brain development. In the last year CT and MRI studies have shown that ventricular enlargement precedes clinical symptoms and is not progressive. These studies support the developmental interpretation. Future studies will need to focus on (a) the mechanisms (Probably genetic) which can cause such developmental anomalies, (b) the neurochemical perturbations occurring as a result of such anomalies and (c) how both relate to clinical symptoms.
Ubiquitin, cell stress and diseases of the nervous system
Authors: LOWE J. , MAYER R. J. 
Published: May 2008

Cells, including those of the nervous system, respond to damage by an increase in the synthesis of a family of proteins called ‘stress proteins’ which are amongst the most conserved gene products in evolution suggesting fundamental roles in cell metabolism. Stress‐induced proteins have functions in normal cells, particularly for the importation of protein into membrane‐limited organelles, and their up‐regulation following stress is thought to be cytoprotective, by protecting proteins and organelles from damage. Ubiquitin is an important protein induced by cell stress. It is only found in nucleated cells and has several known functions; the most investigated being as a co‐factor for the non‐lysosomal intracellular degradation of abnormal or short lived proteins.Morphological studies using immunohistochemistry to localize ubiquitin protein conjugates have revealed that ubiquitin is a component of many of the filamentous inclusion bodies characteristic of neurodegenerative diseases, suggesting activation of a common neuronal response in this type of disease process. Immunohistochemical localization of ubiquitin conjugates has provided a new tool for the sensitive detection of such inclusions and has resulted in the identification of novel inclusion bodies in all cases of motor neuron disease.Preliminary work on enzymes involved in ubiquitin metabolism suggest that there are several possible mechanisms for the formation of inclusion bodies and may provide indirect evidence for the dynamics of inclusion body formation.Work in other areas of pathology indicate important roles for the stress proteins in immune surveillance and autoimmunity and it is likely that the general principles which are currently evolving will also have an impact in neuropathology
The incidence of prenatal brain injury
Authors: SQUIER M. , KEELING J. W. 
Published: May 2008

Recent epidemiological studies have shown that cerebral palsy is only rarely associated with birth asphyxia and that there may be more important causative factors in the prenatal period. For this reason a series of 165 brains of infants who were stillborn or died in the early neonatal period was examined in order to identify the incidence and nature of prenatal brain damage.Seventeen (44%) of the stillborn infants showed evidence of brain damage thought to be related to circulatory disorders. The most frequent abnormality, widespread ischaemic damage to the white matter of the cerebral hemispheres, occurred in 10 (26%). Criteria for white matter ischaemia were reactive astrocytosis, macrophage infiltration, karyorrhexis and endothelial swelling or reduplication. This abnormality was only seen after 27 weeks gestation. In five (13%) of the stillborn infants, haemorrhage was seen in association with ischaemic damage and in only two (5%) did brain haemorrhage occur in utero without evidence of co–existing ischaemic damage.Of the 90 live–born infants, 12 (16%) of those surviving less than 3 days and three (20%) of 15 infants who lived between 3 and 7 days after birth showed ischaemic damage which was of prenatal origin.The most frequent pathological change in the infants studied was white matter gliosis occurring in infants who survived into or beyond the last trimester. This may interfere with normal myelination by diverting glial stem cells into reactive astrocytes and thus reduce the population of oligodendrocytes available to synthesize myelin and so cause permanent neurological damage.
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.
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.
Accumulation of hippocampal cholinergic neurostimulating peptide (HCNP)‐related components in Hirano bodies
Authors: Mitake S. , Ojika K. , Katada E. , Otsuka Y. , Matsukaw N. , Fujimori O. 
Published: May 2008

We have previously isolated from the hippocampus of young rats a novel peptide termed ‘hippocampal cholinergic neurostimulating peptide’ (HCNP) which specifically enhances the cholinergic activity of the septohippocampal system in vitro. Cloning and base sequence analysis of HCNP‐specific cDNA from rat and human cDNA libraries revealed that the 1.1 kDa peptide aligns at the N‐terminal region of its 21 kDa precursor protein. An affinity‐purified rabbit antibody to rat HCNP prepared by us recognizes the C‐terminal domain of the peptide. while an antibody against human HCNP binds to a large portion of the peptide. In this report we show that both antibodies react with HCNP‐related components present in the soluble cytosol fraction of human brain tissue.Immunohistochemical examination of human nervous system tissues from elderly individuals revealed that Hirano bodies in Sommer's sector of the hippocampus were specifically stained by anti‐HCNP antibodies. The number of HCNP‐positive Hirano bodies was greater in patients with Alzheimer's disease than in normal, age‐matched individuals. The immunohistochemical results were substantiated by immunoelectron microscopy. The present findings indicate that HCNP‐related components accumulate in Hirano bodies, suggesting that patients who bear these inclusions may have a disturbance of the septohippocampal cholinergic system, considered to be of importance for learning and memory formation.
Experimental induction of corpora amylacea‐like inclusions in rat astroglia
Authors: Cissé S. , Schipper H. M. 
Published: May 2008

Corpora amylacea (CA) are glycoproteinaceous inclusions that accumulate in the human central nervous system during normal ageing, and to an even greater extent in Alzheimer's disease and other neurodegenera‐tive disorders. They are particularly prominent in subpial and subependymal regions, and are most commonly located within astrocytes and their processes. We previously demonstrated that human CA share many tinctorial and histochemical properties in common with Gomori‐positive cytoplasmic granules which accumulate in periventricular astrocytes of the ageing vertebrate brain and in rat astroglial cultures exposed to the sulphydryl agent, cysteamine (CSH). In the present study, long‐term exposure of neonatal rat astrocyte cultures to CSH resulted in the formation of large spherical, PAS‐positive cytoplasmic inclusions which are highly reminiscent of, if not identical to, human CA.As in the case of human CA and Gomori‐positive astrocyte granules, the CSH‐induced CA‐like inclusions exhibit non‐enzymatic peroxidase activity and consistent immunolabelling with antibodies directed against the mitochondrial protein, sulphite oxidase. Taken together, our findings suggest that progressive mitochondrial damage and macroautophagy play an important role in the biogenesis of CA (and Gomori‐positive granules) in astrocytes of the ageing periventricular brain.
Cytoskeletal changes in cultured human fibroblasts following exposure to 2,5‐hexanedione
Authors: Passarin M. G. , Monaco S. , Ferrari S. , Giannini C. , Rizzuto N. , Moretto G. 
Published: May 2008

M. G. Passarin, S. Monaco, S. Ferrari, C. Giannini, N. Rizzuto and G. Moretto (1996) Neuropathology and Applied Neurobiology 22, 60‐67Cytoskeletal changes in cultured human f ibroblasts following exposure to 2,5‐hexanedioneIn the present study, the effects of the 2,5‐hexanedione (HD) on the various cytoskeletal components of human eukaryotic cells were investigated. Primary cultures of human fibroblasts from three healthy donors were exposed to 2.8 mM HD for 14 days; unexposed cultures were used as controls. At different time intervals, cells were counted and the growth curves compared. After 14 days of treatment, the cultures were processed for immu‐noblotting, immunocytochemistry and ultrastructural studies. As compared to controls, morphological abnormalities induced by HD consisted of modification of the cell shape, formation of tangles composed by 10 nm filaments and cytoplasmic segregation of microtubules and membrane‐bound organelles. By immunocytochemistry, the tangles of cytoplasmic filaments were stained by an antibody specific for vimentin. By immunoblotting, the anti‐vimentin antibody recognized only bands of 50‐60 kDa. Comparison of growth curves between treated and control fibroblasts clearly revealed an interference of HD with the cell cycle. The present results demonstrate that the cytotoxicity of HD is not restricted to intermediate filaments, but affects other cytoskeletal components, such as microtubules, as suggested by the impairment of cell division cycle
Cell death in the normal developing brain, and following ionizing radiation, methyl‐azoxymethanol acetate, and hypoxia‐ischaemia in the rat
Authors: Ferrer I. 
Published: May 2008

SummaryNaturally occurring (programmed) cell death in the developing brain has morphological characteristics of apoptosis and is associated with internucleosomal DNA fragmentation. Apoptosis also plays a role in cell death following hypoxia‐ischaemia in the developing rat brain. Ionizing radiation‐induced cell death in the brain of the young rat has morphological characteristics of apoptosis. is mediated by protein synthesis and is associated with internucleosomal UNA fragmentation. Methylazoxymethanol (MAM) acetate injection in the young rat produces apoptotic cell death in the external granule cell layer of the cerebellum. In addition, strong c‐Jun immunore‐activity is observed in apoptotic cells during normal development and following experimentally induced cell death. Moreover, c‐Jun mRNA induction and de novo c‐Jun protein synthesis, together with activation of c‐Jun/AP‐1, as revealed with gel mobility shift assay, occurs in irradiated animals. Western blotting of total brain homogenates shows a c‐Jun‐immunoreactive band at p39, which corresponds to the molecular weight of c‐Jun. in control rats. However, a thick c‐Jun‐immunoreactive band at about p62, accompanied by a decrease of the p39 band, occurs in irradiated and MAM‐treated rats. A thin band immediately above the thick p62 band, suggestive of c‐Jun phosphorylation, is also observed in treated rats. Taken together, these observations indicate that c‐Jun expression is associated with apoptotic cell death in the developing central nervous system.