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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transplantation of human neural stem cells (NSCs) is a promising potential therapy for neurologic dysfunctions after the hyperacute stage of stroke in humans, but large amounts of human NSCs must be expanded in long-term culture for such therapy. To determine their possible therapeutic potential for human stroke, human fetal neural stem/progenitor cells (NSPCs) (i.e., neurosphere-forming cells) were isolated originally from forebrain tissues of one human fetus, and expanded in long-term neurosphere culture (exceeding 24 weeks), then xenografted into the lesioned areas in the brains of Mongolian gerbils 4 days after focal ischemia. Sensorimotor and cognitive functions were evaluated during the 4 weeks after transplantation. The total infarction volume in the NSPC-grafted animals was significantly lower than that in controls. Approximately 8% of the grafted NSPCs survived, mainly in areas of selective neuronal death, and were costained with antibodies against neuronal nuclei antibody (NeuN), microtubule associated protein (MAP-2), glial fibrillary acidic protein (GFAP), and anti-2'3' cyclic nucleotide 3'-phosphodiesterase (CNPase). Synaptic structures between NSPCs-derived neurons and host neurons were observed. Furthermore, gradual improvement of neurologic functions was observed clearly in the NSPC-grafted animals, compared to that in controls. Human NSPCs, even from long-term culture, remarkably improved neurologic functions after focal ischemia in the Mongolian gerbil, and maintained their abilities to migrate around the infarction, differentiate into mature neurons, and form synapses with host neuronal circuits. These results indicate that in vitro-expanded human neurosphere cells are a potential source for transplantable material for treatment of stroke.
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PMID:Human neural stem/progenitor cells, expanded in long-term neurosphere culture, promote functional recovery after focal ischemia in Mongolian gerbils. 1537 9

Diabetes mellitus increases the risk of central nervous system (CNS) disorders such as stroke, seizures, dementia, and cognitive impairment. The cellular mechanisms responsible for the increased risk of these disorders are incompletely understood. Astrocytes are proving critical for normal CNS function, and alterations in their activity could contribute to diabetes-related disturbances in the brain. We examined the effects of streptozotocin (STZ)-induced diabetes in rats on the level of the astrocyte intermediate filament protein, glial fibrillary acidic protein (GFAP), number of astrocytes, and levels of the astrocyte glutamate transporters, glutamate transporter-1 (GLT-1) and glutamate/aspartate transporter (GLAST), in the cerebral cortex, hippocampus, and cerebellum by Western blotting (WB) and immunohistochemistry (IH). Studies were carried out at 4 and 8 weeks of diabetes duration. Diabetes resulted in a significant decrease in GFAP protein levels (WB) in the hippocampus and cerebellum at 4 weeks and in the cerebral cortex, hippocampus and cerebellum by 8 weeks. Attenuated GFAP immunoreactivity (IH) was evident in the hippocampus, cerebellum and white matter regions such as the corpus callosum and external capsule at both 4 and 8 weeks of diabetes. Astrocyte cell counts of adjacent sections immunoreactive for S-100B were not different between control and diabetic animals. No significant differences were noted in astrocyte glutamate transporter levels in the cerebral cortex, hippocampus, or cerebellum at either time period (WB, IH). With the expanding list of astrocyte functions in the CNS, the role of astrocytes in diabetes-induced CNS disorders clearly warrants further investigation.
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PMID:Effects of diabetes mellitus on astrocyte GFAP and glutamate transporters in the CNS. 1537 52

The long-term (4-month) responses to treatment of stroke in the older adult rat, using rat bone marrow stromal cells (MSCs), have not been investigated. Retired breeder rats were subjected to middle cerebral artery occlusion (MCAo) alone, or injected intravenously with 3 x 10(6) MSCs, at 7 days after MCAo. Functional recovery was measured using an adhesive-removal patch test and a modified neurological severity score. Bromodeoxyuridine, a cell proliferation marker, was injected daily for 14 before sacrifice. Animals were sacrificed 4 months after stroke. Double immunostaining was used to identify cell proliferation and cell types for axons, astrocytes, microglia, and oligodendrocytes. MSC treatment induced significant improvement in neurological outcome after MCAo compared with control rats. MSC treatment reduced the thickness of the scar wall (P < 0.05) and reduced the numbers of microglia/macrophages within the scar wall (P < 0.01). Double staining showed increased expression of an axonal marker (GAP-43), among reactive astrocytes in the scar boundary zone and in the subventricular zone in the treated rats. Bromodeoxyuridine in cells preferentially colocalized with markers of astrocytes (GFAP) and oligodendrocytes (RIP) in the ipsilateral hemisphere, and gliogenesis was enhanced in the subventricular zone of the rats treated with MSCs. This is the first report to show that MSCs injected at 7 days after stroke improve long-term neurological outcome in older animals. Brain tissue repair is an ongoing process with reactive gliosis, which persists for at least 4 months after stroke. Reactive astrocytes responding to MSC treatment of ischemia may also promote axonal regeneration during long-term recovery.
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PMID:Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells. 1554 Feb 31

Rodent models of stroke are often used to investigate the mechanisms that lead to ischemic neuronal damage. In this study, we used a model of cerebral hypoxia with ischemia to produce unilateral damage in C57Bl/6 mice. Lesion volume, ascertained by TTC staining, increased with longer durations of hypoxia. Additionally, cresyl violet, TUNEL, and FluoroJade staining showed a statistically significant increase in cellular damage in the ipsilateral cortex, CA1 pyramidal layer, and dentate gyrus of the hippocampus of ipsilateral hypoxic/ischemic tissue versus sham tissue. Astrocyte reactivity, determined by GFAP staining, was significantly higher in the ipsilateral H/I cortex and contralateral hippocampus compared to sham cortex and hippocampus, respectively. Increased microglia activation was evident in the H/I-treated cortex and hippocampus versus sham cortex and hippocampus, particularly within areas undergoing degeneration. To examine whether this model produces motor deficits, a battery of tests were administered before and after hypoxia. Following 45 min H/I, locomotor activity, rotarod performance and performance on an inverted wire hang test were all significantly decreased. These data indicate that the histological evidence of neuronal damage is consistent with functional deficits and suggest that this model may be useful for investigating strategies designed to protect neurons from hypoxia/ischemia-induced damage.
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PMID:Characterization of cellular and neurological damage following unilateral hypoxia/ischemia. 1554 86

To identify biochemical markers for carotid stroke outcome, blood serum levels of inflammation markers (C-reactive protein, orosomucoid, soluble p-selectin) and autoantibodies (AAB) to neurospecific antigens (glial fibrillary acidic protein, neuron specific enolase, S-100 protein) were studied in 27 patients (mean age 64 +/- 6 years) with acute ischemic stroke in inner carotid artery system on day 1-2 and 21 of the disease onset. To day 21, patients with good rehabilitation of neurological functions (group 1) demonstrated a decrease of C-reactive protein and soluble p-selectin concentrations, and unfavorable disease course was associated with a significant (p<0.05) increase of concentrations of these indices. On day 1 and 7, a level of AAT to glial fibrillary acidic protein was higher (p<0.05) in group 1 than in that with minimal rehabilitation and to day 21 it decreased relatively the baseline level. At the same time, patients with minimal rehabilitation had a stable AAT level. On day 7, the AAT level correlated with expression of neurological deficit on day 21 (r=0.510; p=0.019). No stroke-course-dependent differences were found in dynamics of orosomucoid as well as of AAT to neuron specific enolase and S-100 protein levels.
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PMID:[Markers of inflammation, autoantibodies to neurospecific antigens and outcome in patients with acute ischemic stroke]. 1562 89

We have previously demonstrated that neuregulin-1 (NRG-1) is upregulated and is neuroprotective in ischemic brain injury, however the expression and localization of its receptors during ischemia has not been investigated. Therefore, we used a rat middle cerebral artery occlusion (MCAO) model to examine the distribution of erbB receptors following ischemic stroke. Like neuregulin-1, we observed a dramatic induction of erbB4 in the peri-infarct regions of the ipsilateral cortex 24 h following MCAO. Using Fluoro-Jade B (FJB) staining as a marker of neurodegeneration, erbB4 was upregulated in FJB-positive cells, suggesting that erbB receptors are induced in injured neurons. The increase in erbB receptors was seen in neurons and a subpopulation of macrophages/microglia. There was no erbB co-localization with GFAP-positive astrocytes. These results demonstrate that erbB receptors are upregulated in neurons and macrophages/microglia following ischemic stroke and may be involved in neuroprotection and repair.
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PMID:Upregulation of erbB receptors in rat brain after middle cerebral arterial occlusion. 1569 57

Immunochemical staining techniques are commonly used to assess neuronal, astrocytic and microglial alterations in experimental neuroscience research, and in particular, are applied to tissues from animals subjected to ischemic stroke. Immunoreactivity of brain sections can be measured from digitized immunohistology slides so that quantitative assessment can be carried out by computer-assisted analysis. Conventional methods of analyzing immunohistology are based on image classification techniques applied to a specific anatomic location at high magnification. Such micro-scale localized image analysis limits one for further correlative studies with other imaging modalities on whole brain sections, which are of particular interest in experimental stroke research. This report presents a semi-automated image analysis method that performs convolution-based image classification on micro-scale images, extracts numerical data representing positive immunoreactivity from the processed micro-scale images and creates a corresponding quantitative macro-scale image. The present method utilizes several image-processing techniques to cope with variances in intensity distribution, as well as artifacts caused by light scattering or heterogeneity of antigen expression, which are commonly encountered in immunohistology. Micro-scale images are composed by a tiling function in a mosaic manner. Image classification is accomplished by the K-means clustering method at the relatively low-magnification micro-scale level in order to increase computation efficiency. The quantitative macro-scale image is suitable for correlative analysis with other imaging modalities. This method was applied to different immunostaining antibodies, such as endothelial barrier antigen (EBA), lectin, and glial fibrillary acidic protein (GFAP), on histology slides from animals subjected to middle cerebral artery occlusion by the intraluminal suture method. Reliability tests show that the results obtained from immunostained images at high magnification and relatively low magnification are virtually the same.
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PMID:Semi-automated image processing system for micro- to macro-scale analysis of immunohistopathology: application to ischemic brain tissue. 1578 Aug 92

This study tested the application of an immunoisotopic assay for immunohistochemical localization and quantification of proteins in brain sections from rats without or with transient focal ischemia. We assessed the hypothesis that measurements of protein levels in injured brain determined by an isotopic assay using [(125)I]-protein A have greater reliability than those made by conventional immunoperoxidase labeling using diaminobenzidine. Quantification of immunoreactivities for glial fibrillary acidic protein (GFAP), glutamate transporter-1 (GLT-1) and heat shock protein-70 (HSP-70) was determined by optical density signal in the immunoisotopic and immunoperoxidase assays. In ischemic brain, the immunoisotopic assay detected protein increases (cortical penumbra HSP-70, 151+/-6%), protein decreases (cortical ischemic core GLT-1, 61+/-6%) and no changes in GFAP levels compared to controls animals. These results differed from the protein levels found by the immunoperoxidase assay, which showed elevated HSP-70, GLT-1 and GFAP in all ischemic regions. We conclude that nonspecific immunosignal confounds assessments of protein expression in injured brain and that the immunoisotopic method is a valid approach to regionally localize and quantify proteins after brain injury. The disadvantage of the falsely positive overestimation of protein immunoreactivity after stroke with the immunoperoxidase method has to be weighted with the advantage of the cellular resolution.
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PMID:In situ immunoradiographic method for quantification of specific proteins in normal and ischemic brain regions. 1581 55

Stroke patients have increased levels of endothelin-1 (ET-1), a strong vasoconstrictor, in their plasma or cerebrospinal fluid. Previously, we showed high level of ET-1 mRNA expression in astrocytes after hypoxia/ischemia. It is unclear whether the contribution of ET-1 induction in astrocytes is protective or destructive in cerebral ischemia. Here, we generated a transgenic mouse model that overexpress ET-1 in astrocytes (GET-1) using the glial fibrillary acidic protein promoter to examine the role of astrocytic ET-1 in ischemic stroke by challenging these mice with transient middle cerebral artery occlusion (MCAO). Under normal condition, GET-1 mice showed no abnormality in brain morphology, cerebrovasculature, absolute cerebral blood flow, blood-brain barrier (BBB) integrity, and mean arterial blood pressure. Yet, GET-1 mice subjected to transient MCAO showed more severe neurologic deficits and increased infarct, which were partially normalized by administration of ABT-627 (ET(A) antagonist) 5 mins after MCAO. In addition, GET-1 brains exhibited more Evans blue extravasation and showed decreased endothelial occludin expression after MCAO, correlating with higher brain water content and increased cerebral edema. Aquaporin 4 expression was also more pronounced in astrocytic end-feet on blood vessels in GET-1 ipsilateral brains. Our current data suggest that astrocytic ET-1 has deleterious effects on water homeostasis, cerebral edema and BBB integrity, which contribute to more severe ischemic brain injury.
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PMID:Endothelin-1 overexpression leads to further water accumulation and brain edema after middle cerebral artery occlusion via aquaporin 4 expression in astrocytic end-feet. 1581 85

Both increased and decreased testosterone levels have been reported to correlate with poor outcome after acute ischemic stroke. The present study focused on the role of testosterone during recovery from neurological deficits in a rat focal ischemia model. Castrate male rats were subjected to behavioral tests after 90 min of middle cerebral artery occlusion (MCAO). On day 7 post-MCAO, neurological deficit-matched rats were assigned to a treatment group implanted with subcutaneous testosterone pellets or a control group implanted with sham cholesterol pellets. After 4 weeks post-MCAO, the average infarct volume was not significantly different between the two groups. Rats in the testosterone group demonstrated significantly earlier improvement in neurological deficits and shortened latency of adhesive tape removal compared with the control group as analyzed by Wilcoxon signed ranks test. Walking on parallel bars improved in both groups with a trend towards early recovery observed in the testosterone group. Biased left body swings persisted during the test period in both groups post-MCAO. Serum testosterone was within physiological levels in the treatment group but was not detectable in the control group by radioimmunoassay. GAP-43 and synaptophysin expression did not differ between groups. Less GFAP expression and reactive astrocyte hypertrophy were found around the infarct area in testosterone-treated rats compared with control rats. In conclusion, testosterone replacement post-MCAO accelerated functional recovery in castrate rats, suggesting a potential therapeutic role for testosterone replacement in stroke recovery.
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PMID:Effect of testosterone on functional recovery in a castrate male rat stroke model. 1586 33


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