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

Flow studies using dynamic CT and xenon (Xe) CT were carried out in 25 patients with ischaemic stroke in the territory of the middle cerebral artery to define the clinical characteristics of cerebral ischaemia at a chronic stage. The parameter of peak height/mean transit time (PH/MTT) obtained from dynamic CT can provide an accurate index for blood circulation in the cerebral vascular bed. Xe CT measurements revealed various kinds of ischaemia around the infarction even in the chronic stages. In mild ischaemia of more than 30 ml/100 g/min, reduction of cerebral blood flow (CBF) was well correlated to the PH/MTT. However, in severe ischaemia between 20 and 30 ml/100 g/min, changes of CBF were no longer correlated with the PH/MTT. There were cases showing severe reduction of CBF but which showed sufficient blood circulation (moderate value of PH/MTT). Mild reductions of CBF in parallel with decreased blood supply were often found in the peri-infarct area of infarctions in the centrum semiovale. On the other hand, infarctions in the cortico-subcortical region showed severe ischaemia, in even where blood circulation was relatively well sustained.
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PMID:Reversibility of cerebral ischaemia. Dynamic and xenon computed tomography study on ischaemic cerebrovascular disease. 794 95

Removal of extracellular glutamate at synapses, by specific high-affinity glutamate transporters, is critical to prevent excitotoxic injury to neurons. Oxidative stress has been implicated in the pathogenesis of an array of prominent neurodegenerative conditions that involve degeneration of synapses and neurons in glutamatergic pathways including stroke, and Alzheimer's, Parkinson's and Huntington's diseases. Although cell culture data indicate that oxidative insults can impair key membrane regulatory systems including ion-motive ATPases and amino acid transport systems, the effects of oxidative stress on synapses, and the mechanisms that mediate such effects, are largely unknown. This study provides evidence that 4-hydroxynonenal, an aldehydic product of lipid peroxidation, mediates oxidation-induced impairment of glutamate transport and mitochondrial function in synapses. Exposure of rat cortical synaptosomes to 4-hydroxynonenal resulted in concentration- and time-dependent decreases in [3H]glutamate uptake, and mitochondrial function [assessed with the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)]. Other related aldehydes including malondialdehyde and hexanal had little or no effect on glutamate uptake or mitochondrial function. Exposure of synaptosomes to insults known to induce lipid peroxidation (FeSO4 and amyloid beta-peptide) also impaired glutamate uptake and mitochondrial function. The antioxidants propyl gallate and glutathione prevented impairment of glutamate uptake and MTT reduction induced by FeSO4 and amyloid beta-peptide, but not that induced by 4-hydroxynonenal. Western blot analyses using an antibody to 4-hydroxynonenal-conjugated proteins showed that 4-hydroxynonenal bound to multiple cell proteins including GLT-1, a glial glutamate transporter present at high levels in synaptosomes. 4-Hydroxynonenal itself induced lipid peroxidation suggesting that, in addition to binding directly to membrane regulatory proteins, 4-hydroxynonenal potentiates oxidative cascades. Collectively, these findings suggest that 4-hydroxynonenal plays important roles in oxidative impairment of synaptic functions that would be expected to promote excitotoxic cascades.
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PMID:4-Hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes. 927 86

Ebselen is a selenium compound that have glutathione peroxidase-like activity which is neuroprotective in acute stroke ischemia. The efficacy of ebselen to prevent excitotoxicity provoked by glutamate in cerebellar granule neurons was investigated at various time points and concentrations. Simultaneous addition of ebselen with glutamate decreased neuronal death and was completely reversed by 3 microM of ebselen (3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and propidium iodide assays). However, when 1 microM of ebselen was added with glutamate and remained in the culture medium until 24 or 48 h, the neuronal survival increased to the control. The mechanism proposed for neuroprotection was the ability of ebselen to prevent lipoperoxidation provoked by glutamate. The present findings propose to amplify the use of ebselen in others neurodegenerative disorders involving glutamatergic system.
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PMID:Ebselen prevents excitotoxicity provoked by glutamate in rat cerebellar granule neurons. 1116 74

N-Methyl-D-aspartate (NMDA) receptor-mediated cell death is complex, probably involving elements of necrosis and apoptosis. The mechanisms underlying this phenomenon are incompletely understood but have been suggested to involve reactive oxygen species such as nitric oxide and superoxide anion (O(2)) and nuclear factor-kappaB (NF-kappaB) signaling. In this study, we used a selective nonpeptidyl superoxide dismutase mimetic (M40403) and SN50, a peptide inhibitor of NF-kappaB translocation, to investigate the role of O(2) and the potential downstream signaling molecules in cell death induced by activation of the NMDA receptor. Application of NMDA to a mixed neuronal/glial forebrain culture resulted in an early increase in the release of cytoplasmic lactate dehydrogenase (LDH), which peaked at 4 h. This was followed by a reduction in mitochondrial metabolism of the dye MTT [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide] that continued to decrease throughout the 20-h exposure. A substantial increase in DNA fragmentation as measured by an enzyme-linked immunosorbent assay (ELISA) specific for DNA-associated histone proteins (nucleosomes) was observed at 7 and 20 h. M40403 and SN50 blocked NMDA-induced changes in LDH release at 2, 4, and 20 h, MTT metabolism at 4 and 20 h, and DNA fragmentation at 20 h as measured by the ELISA and by an increase in terminal dUTP-nick end labeling. M40403 also prevented NMDA-induced nuclear transport of NF-kappaB and increased expression of Bax relative to Bcl-X(L). SN50 was also able to block NMDA-induced cell death as well as the increased Bax/Bcl-X(L) ratio. Time course studies and experiments with SN50 and M40403 suggest that O(2) production and NF-kappaB translocation may be involved in necrosis and apoptosis, but the latter also requires an increased expression of Bax. The ability of M40403 to prevent NMDA-induced cell death relatively early in this cascade suggests its potential therapeutic utility in central nervous systems diseases such as stroke that are associated with increased NMDA receptor-mediated production of O(2).
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PMID:The role of superoxide and nuclear factor-kappaB signaling in N-methyl-D-aspartate-induced necrosis and apoptosis. 1196 Oct 46

Alzheimer's disease (AD) is more prevalent following an ischemic or hypoxic episode, such as stroke. Indeed, brain levels of amyloid precursor protein (APP) and the cytotoxic amyloid beta peptide (Abeta) fragment are enhanced in these patients and in animal models following experimental ischaemia. We have investigated the effect of chronic hypoxia (CH; 2.5% O2, 24 h) on processing of APP in the human neuroblastoma, SH-SY5Y. We demonstrate that constitutive and muscarinic-receptor-enhanced secretion of the alpha-secretase cleaved fragment of APP, sAPPalpha, was reduced by approximately 60% in CH cells. The caspase inhibitor BOC-D(Ome)FMK did not reverse this effect of CH, and CH cells were as viable as controls, based on MTT assays. Thus, loss of sAPPalpha is not related to cell death or caspase processing of APP. Pre-incubation with antioxidants did not reverse the effect of CH, and the effect could not be mimicked by H2O2, discounting the involvement of reactive oxygen species in hypoxic loss of sAPPalpha. CH did not affect muscarinic activation of extracellular-signal regulated kinase. However, expression of ADAM 10 (widely believed to be alpha-secretase) was decreased approximately 50% following CH. Thus, CH selectively decreases processing of APP by the alpha-secretase pathway, most likely by decreasing levels of ADAM 10.
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PMID:Altered processing of amyloid precursor protein in the human neuroblastoma SH-SY5Y by chronic hypoxia. 1247 81

Ebselen is a seleno organic compound with antioxidant and anti-inflammatory properties, which is under clinical trials for the treatment of ischemic stroke. In this study, we attempted to correlate the protective effects of ebselen and the inducible nitric oxide synthase (iNOS) immunocontent in hippocampal slices submitted to oxygen-glucose deprivation (OGD), since the exacerbated production of nitric oxide by iNOS plays a role in the mechanisms of cellular death in ischemic insults. Ebselen (10 microM) protected slices from the deleterious effects of OGD (as assessed by MTT assay) only when present during all the recovery period (180 min). Moreover, ebselen added 5 and 15 min after the beginning of recovery only partially protected the slices from cellular death, while when added 30 min after the beginning of recovery no protection was observed. OGD increased the immunocontent of iNOS, and this increase was abolished also only when ebselen was present during all the recovery period. Our results indicate that the neuroprotective effect of ebselen could be related to this decrease in the iNOS immunocontent.
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PMID:Neuroprotective effect of ebselen on rat hippocampal slices submitted to oxygen-glucose deprivation: correlation with immunocontent of inducible nitric oxide synthase. 1285 May 58

Atherosclerosis and its complications such as stroke, myocardial infraction and peripheral vascular disease, remain the major causes of morbidity and mortality in the world. Studies have showed that chemokines and adhesion molecules are involved in causing atherosclerosis by promoting directed migration of inflammatory cells. Monocyte chemoattractant protein-1 (MCP-1) is one of the key factors critical for the initiating and developing of atherosclerotic lesions. IL-8, a CXC chemokine, stimulates neutrophil chemotaxis. Aspirin is the most common drug used to prevent the complications of atherosclerosis such as stroke and coronary heart disease. In this study, we found that aspirin inhibited TNF-alpha (10 ng/ml)-induced MCP-1 and IL-8 expression at the RNA and protein levels in human umbilical vein endothelial cells (HUVECs), monocyte adhesion and transmigration, and that its inhibitory effects were not due to decreased HUVEC viability as assessed by MTT test. Aspirin at the dose as low as 10 microg/ml significantly inhibited the release of TNF-stimulated MCP-1 by 29.1% (P = 0.008) and IL-8 by 26.9% (P = 0.0146) as compared to TNF-stimulated release. Antibodies pretreatment were likely to decrease the production of MCP-1 (P < 0.0001) and IL-8 (P < 0.0001). Furthermore, aspirin (10 microg/ml) inhibited U937 cell adhesion by a 13.4% (P = 0.0119) inhibition as compared to TNF-stimulated alone. Finally, at higher concentration, aspirin also inhibited U937 migration to HUVEC by 89.1% (P = 0.0475) as compared to TNF-stimulated alone. These results in our study suggest that aspirin inhibits TNF-alpha stimulated MCP-1 and IL-8 release in HUVECs, for its additional therapeutic effects of aspirin in causing atherosclerosis.
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PMID:Aspirin inhibits monocyte chemoattractant protein-1 and interleukin-8 expression in TNF-alpha stimulated human umbilical vein endothelial cells. 1513 50

Mitochondrial dysfunction and oxidative stress are often linked to various neurodegenerative disorders including ischemic stroke and Huntington's disease (HD). S-Nitrosoglutathione (GSNO) is an endogenous nitric oxide carrier recently identified as a potent antioxidant capable of neutralizing oxidative stress. In the present study, we explore the neuroprotective effects of GSNO against metabolic insults induced by 3-nitropropionic acid (3-NP), a mitochondrial complex II inhibitor commonly used as a pharmacological model for HD, in primary culture of fetal rat cortical and striatal neurons. Application of GSNO (1-5 microM) substantially reduced neuronal loss caused by 3-NP (1-5 mM) exposure based on MTT reduction, lactate dehydrogenase (LDH) release, and Hoechst staining assays. The protective effect of GSNO appeared to be more potent than N-acetyl-l-cysteine (NAC), a glutathione precursor, at the same concentrations. These results suggest that manipulation of GSNO metabolism may exert protective effects against mitochondrial dysfunction often observed in neurodegenerative disorders.
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PMID:Protective effects of S-nitrosoglutathione against neurotoxicity of 3-nitropropionic acid in rat. 1515 20

Alcoholic infusions of Ptychopetalum olacoides Bentham (PO, Olacaceae) are used in traditional medicine by patients presenting age associated symptoms and those recovering from stroke. The aim of this study is to evaluate the neuroprotective properties of PO ethanol extract (POEE) using hippocampal slices from Wistar rats exposed to oxygen and glucose deprivation (OGD, followed by reoxygenation). Mitochondrial activity, an index of cell viability, was assessed by the MTT assay; in addition, the free radicals content was estimated by the use of dichlorofluorescein diacetate as probe. The OGD ischemic condition significantly impaired cellular viability, and increased free radicals generation. In non-OGD slices, incubation with POEE (0.6 microg/ml) increased (approximately 40%) mitochondrial activity, without affecting free radicals levels. In comparison to OGD controls, slices incubated with POEE (0.6 microg/ml) during and after OGD exposure had significantly increased cellular viability. In addition, at this same concentration, POEE prevented the increase of free radicals content induced by OGD. In view of the fact that respiratory chain inhibition and increased generation of free radicals are major consequences of the ischemic injury, this study suggests that Ptychopetalum olacoides contains useful neuroprotective compounds and, therefore, deserves further scrutiny.
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PMID:Neuroprotective effects of Ptychopetalum olacoides Bentham (Olacaceae) on oxygen and glucose deprivation induced damage in rat hippocampal slices. 1530 33

Perfusion-weighted imaging (PWI) measures can predict tissue outcome in acute ischemic stroke. Accuracy might be improved if differential tissue susceptibility to ischemia is considered. We present a novel voxel-by-voxel analysis to characterize cerebral blood flow (CBF) separately in gray (GM) and white matter (WM). Ten patients were scanned with inversion-recovery spin-echo EPI (IRSEPI), diffusion-weighted imaging (DWI), PWI<6 h from onset and fluid attenuated inversion-recovery (FLAIR) at 30 days. Image processing included coregistration to PWI, automatic segmentation of IRSEPI into GM, WM and CSF and semiautomatic segmentation of DWI/FLAIR to derive the acute and 30-day lesions. Five tissue compartments were defined: (1) 'Core' (abnormal acutely and at 30 days), (2) 'Growth' (or 'infarcted penumbra', abnormal only at 30 days), (3) 'Reversed' (abnormal acutely but normal at 30 days), (4) 'MTT-Delayed ' (tissue with delayed mean transit time but not part of the acute or 30-day lesion), and (5) 'Normal' brain. Cerebral blood flow in GM and WM of each compartment was obtained from quantitative maps. Gray matter and WM mean CBF in the growth region differed by 5.5 mL/100 g min (P=0.015). Mean CBF also differed significantly within normal and MTT-Delayed compartments. The difference in the reversed region approached statistical significance. In core, GM and WM CBF did not differ. The results suggest separate ischemic thresholds for GM and WM in stroke penumbra.
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PMID:A novel method to derive separate gray and white matter cerebral blood flow measures from MR imaging of acute ischemic stroke patients. 1588 45


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