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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to clarify whether pre-exposure to hypoxia influences neuronal death following transient cerebral ischaemia. Twenty gerbils were exposed to 10% oxygen in a chamber for 3 weeks. The other control gerbils (n = 20) were fed in normoxia for 3 weeks. Both carotid arteries in the neck were occluded with aneurysm clips for 5 minutes under halothane anaesthesia in 30 gerbils, recirculated and then fed in normoxia. Five animals in both groups were sacrificed before, and 2, 4, and 7 days after surgery. The animals were fixed with 4% paraformaldehyde and histological study was performed. Immunohistochemical study was also done with antibodies against basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). The neuronal death in the hippocampus was more severe in the hypoxic group. Expression of both bFGF and VEGF was obvious in the cingulate cortex, corpus callosum and internal capsule before clipping in the hypoxic group, but not observed in the normoxic group before clipping. We observed the expression of both bFGF and VEGF widely in the brain at 2 and 4 days after recirculation in both groups. The expression in the hypoxic group was much more prominent than that in the normoxic group. These expressions were not observed at 7 days in both groups. Pre-exposure to hypoxia followed by transient cerebral ischaemia accelerated neuronal death in the hippocampus, and induced the more obvious expression of both VEGF and bFGF compared with those in the normoxic group.
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PMID:Transient cerebral ischaemia in Mongolian gerbils pre-exposed to hypoxia. 926 62

Several growth factors have been implicated in the pathogenesis of Alzheimer's disease (AD). We considered whether the vascular endothelial growth factor (VEGF) is involved in the vascular pathology associated with most cases of AD. We observed enhanced VEGF immunoreactivity in clusters of reactive astrocytes in the neocortex of subjects with AD compared to elderly controls. VEGF reactivity was also noted in walls of many large intraparenchymal vessels and diffuse perivascular deposits. In addition, we established that astrocytic and perivascular VEGF reactivity was enhanced in cerebral cortex of rats subjected to cerebral ischemia and to chronic hypoxia; experimental conditions known to be associated with astrogliosis and angiogenesis. We suggest the increased VEGF reactivity, also observed in infarcted human brain tissue, implicates compensatory mechanisms to counter insufficient vascularity or reduced perfusion (oligemia) apparent in AD.
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PMID:Vascular endothelial growth factor in Alzheimer's disease and experimental cerebral ischemia. 979 65

Using a reproducible two-vessel occlusion model for forebrain ischemia in rats, we investigated the temporal and spatial changes of vascular endothelial growth factor (VEGF) expression after transient forebrain ischemia with Northern blot analysis and in situ hybridization. Northern blot analysis revealed that VEGF mRNA of the hippocampus was increased from 12 h after reperfusion, with a peak at 1 day. In situ hybridization and double labeling for VEGF mRNA and glial fibrillary acidic protein showed a transient induction of VEGF mRNA in the neurons of the hippocampus from 12 h of reperfusion with a peak at 1 day, and in the astrocytes of the hippocampus, caudoputamen, thalamus and cortical regions at 1 day. After 3 days, no more VEGF signal was detected. Our results demonstrate that astrocytes and neurons each upregulate VEGF mRNA in different temporal and spatial patterns after transient forebrain ischemia in the rat, and these patterns appear to be different from those in transient focal cerebral ischemia.
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PMID:Expression of vascular endothelial growth factor mRNA following transient forebrain ischemia in rats. 1032 80

This study examined vascular endothelial growth factor (VEGF) expression in rat brain after reversible global cerebral ischemia produced by cardiac arrest and resuscitation. Three alternative splicing forms, VEGF(188), VEGF(164) and VEGF(120), were observed in cortex, hippocampus and brainstem by RT-PCR analysis. After 24 h of recovery from cardiac arrest, mRNA levels corresponding to VEGF(188) and VEGF(164) were significantly increased by about double in all the regions analyzed. These mRNA levels remained elevated at 24 and 48 h of recovery but returned to basal expression after 7 days of recovery. Changes in VEGF(120) expression after cardiac arrest did not reach statistical significance. VEGF protein expression measured by Western blot was also increased by about double at 24 and 48 h of recovery but returned to control levels after 7 days of recovery. VEGF immunohistochemistry localized this increased expression mostly associated with astrocytes. Considering its biological activity, VEGF induction after cardiac arrest and resuscitation may be responsible for the increased vascular permeability and the resultant vasogenic edema, found 24-48 h after reversible global ischemia.
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PMID:Vascular endothelial growth factor upregulation in transient global ischemia induced by cardiac arrest and resuscitation in rat brain. 1064 Jun 78

The angiopoietin/Tie receptor system may contribute to angiogenesis and vascular remodeling by mediating interactions of endothelial cells with smooth muscle cells and pericytes. The temporal expression of angiopoietin-1 (Angpo-1), angiopoietin-2 (Angpo-2), Tie-1, and Tie-2 mRNA was studied in a focal cerebral ischemia model in rats. The cDNA fragments obtained from reverse transcription polymerase chain reaction amplification were cloned and used as a probe to detect individual genes. Northern blot analysis showed a delayed increase of a 4.4-kb Angpo-1 transcript for up to 2 weeks after ischemia, eightfold higher than the values of the sham-operated controls. A biphasic expression of a 2.4-kb Angpo-2 transcript was noted, peaking at 24 hours (6.4-fold) and 2 weeks (4.6-fold) after ischemia. The expression of Tie-2 mRNA (4.3 kb), a receptor for Angpo-1, and Tie-1 mRNA (4.3 kb) also increased starting 24 hours after reperfusion and remained elevated for up to 2 weeks after ischemia. The temporal profiles of the expression of these genes were different from those of other angiogenic genes such as basic fibrobast growth factor/fibroblast growth factor receptor and vascular endothelial growth factor/vascular endothelial growth factor receptor and proteolytic enzymes (tissue-type plasminogen activator and urokinase plasminogen activator) and their inhibitors (plasminogen activator inhibitor-1). The expression patterns of these genes could be related to progressive tissue liquefaction and neovascularization after ischemia in this stroke model. Differential expression of these angiogenesis genes suggests the involvement of complex regulatory mechanisms that remain to be characterized.
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PMID:Induction of angiopoietin and Tie receptor mRNA expression after cerebral ischemia-reperfusion. 1069 77

We investigated the hypothesis that hypoxia induces angiogenesis and thereby may counteract the detrimental neurological effects associated with stroke. Forty-eight to seventy-two hours after permanent middle cerebral artery occlusion we found a strong increase in the number of newly formed vessels at the border of the infarction. Using the hypoxia marker nitroimidazole EF5, we detected hypoxic cells in the ischemic border of the neocortex. Expression of vascular endothelial growth factor (VEGF), which is the main regulator of angiogenesis and is inducible by hypoxia, was strongly up-regulated in the ischemic border, at times between 6 and 24 hours after occlusion. In addition, both VEGF receptors (VEGFRs) were up-regulated at the border after 48 hours and later in the ischemic core. Finally, the two transcription factors, hypoxia-inducible factor-1 (HIF-1) and HIF-2, known to be involved in the regulation of VEGF and VEGFR gene expression, were increased in the ischemic border after 72 hours, suggesting a regulatory function for these factors. These results strongly suggest that the VEGF/VEGFR system, induced by hypoxia, leads to the growth of new vessels after cerebral ischemia. Exogenous support of this natural protective mechanism might lead to enhanced survival after stroke.
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PMID:Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. 1070 12

Vascular endothelial growth factor is an angiogenic and neurotrophic peptide whose expression is transcriptionally induced in hypoxic tissues through the action of hypoxia-inducible factor-1alpha. To determine if this signaling pathway is activated in the ischemic brain, and might therefore participate in adaptive processes such as angiogenesis and neuroprotection, we examined the expression of vascular endothelial growth factor and hypoxia-inducible factor-1alpha in cerebral cortex and hippocampus following transient global cerebral ischemia in the rat. Northern analysis showed ischemia-inducible expression of multiple vascular endothelial growth factor messenger ribonucleic acid splice variants between 4 and 24h. Western analysis and immunocytochemistry demonstrated the concerted induction of vascular endothelial growth factor and hypoxia-inducible factor-1alpha in the same, apparently neuronal, cells in vulnerable regions of cortex and hippocampus after 15min of ischemia, which persisted for as long as 4 to 72h of reperfusion. These findings demonstrate that hypoxia-sensitive vascular endothelial growth factor signaling can be induced in neurons in global cerebral ischemia in vivo, and are consistent with the hypothesis that ischemic insults trigger hypoxia-sensing and adaptive downstream molecular responses in central neurons.
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PMID:Induction of vascular endothelial growth factor and hypoxia-inducible factor-1alpha by global ischemia in rat brain. 1102 49

Vascular endothelial growth factor is an angiogenic peptide that binds to tyrosine kinase receptors on target cells to activate signal transduction pathways involving phosphatidylinositol 3'-kinase and the serine-threonine protein kinase, Akt. To determine whether this signaling pathway is activated in cerebral ischemia, we examined the expression of vascular endothelial growth factor receptors 1 and 2, and phosphatidylinositol 3'-kinase-activated phospho-Akt, in the cerebral cortex and hippocampus following transient global cerebral ischemia in the rat. Western blot analysis and immunocytochemistry demonstrated induction of vascular endothelial growth factor receptor 1 and 2 expression, and of anti-phosphatidylinositol 3'-kinase-immunoprecipitated phospho-Akt, in vulnerable regions of the cortex and hippocampus after 15 min of global ischemia and 4-72 h of reperfusion. These findings demonstrate that vascular endothelial growth factor receptors and receptor-coupled signal transduction pathways are induced in ischemic brain in vivo, and could therefore participate in endogenous neuroprotective responses to ischemia.
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PMID:Induction of vascular endothelial growth factor receptors and phosphatidylinositol 3'-kinase/Akt signaling by global cerebral ischemia in the rat. 1103 5

Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates changes in gene expression in response to changes in cellular oxygen concentrations. HIF-1 is a heterodimer consisting of an oxygen-regulated HIF-1 alpha subunit and a constitutively expressed HIF-1 beta subunit. In mice, complete HIF-1 alpha deficiency results in embryonic lethality at midgestation because of cardiac and vascular malformations. Analyses of animal and cell culture models as well as human tissue have provided evidence that HIF-1 plays important roles in the pathophysiology of preeclampsia, intrauterine growth retardation, hypoxia-mediated pulmonary hypertension, and cancer. HIF-1 promotes neovascularization in response to myocardial or retinal ischemia by activating transcription of the gene encoding vascular endothelial growth factor. HIF-1 may also mediate the protective response to cerebral ischemia known as late-phase preconditioning.
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PMID:Hypoxia-inducible factor 1: control of oxygen homeostasis in health and disease. 1132 42

During development, neuropilin-1 is a receptor for semaphorin 3a-mediated axonal guidance and for vascular endothelial growth factor (VEGF) promotion of angiogenesis. The authors measured neuropilin-1 expression in the adult ischemic brain using Northern blot, in situ hybridization, and immunohistochemistry. Neuropilin-1 mRNA was significantly up-regulated as early as 2 hours and persisted at least 28 days after focal cerebral ischemia. Acute up-regulation of neuropilin-1 mRNA primarily localized to the ischemic neurons. A marked increase in both mRNA and protein of neuropilin-1 was detected in endothelial cells of cerebral blood vessels at the border and in the core of the ischemic lesion 7 days after ischemia, and neuropilin-1 gene expression persisted on these vessels for at least 28 days after ischemia. In these areas, neovascularization was detected using three-dimensional reconstructed images obtained from laser scanning confocal microscopy. Activated astrocytes also exhibited neuropilin-1 immunoreactivity during 7 to 28 days of ischemia. Double immunofluorescent staining showed colocalization of neuropilin-1 and VEGF to cerebral blood vessels and activated astrocytes. These data suggest that in addition to its role in axonal growth, up-regulation of neuropilin-1, in concert with VEGF and its receptors, may contribute to neovascular formation in the adult ischemic brain.
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PMID:Up-regulation of neuropilin-1 in neovasculature after focal cerebral ischemia in the adult rat. 1133 64


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