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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cortical spreading depression (CSD) was induced in male Wistar rats by applying 2 M KCl to the frontal cortex of one hemisphere for 2 h. Saline was applied to the contralateral cortex in the same manner. Following recovery for 24 h, bilateral forebrain ischemia was induced for 6 min, and the animals were permitted to survive for 6 days for assessment of histopathology. The number of necrotic neurons was counted in the cerebral cortex, striatum, and hippocampus of both hemispheres. In separate sets of animals, the effects of KCl application on cortical direct current (DC) potential and regional expression of c-fos mRNA and 72-kDa heat shock protein (hsp72) mRNA were determined. Forebrain ischemia induced selective neuronal necrosis in both hemispheres, but the number of necrotic neurons in the cerebral cortex ipsilateral to the application of KCl was significantly smaller than that in the contralateral cortex (p < 0.02, Wilcoxon signed rank test, n = 7). In the striatum and hippocampus, there were no significant differences in neuronal necrosis between hemispheres. Application of KCl for 2 h induced 11 +/- 2 (mean +/- SD, n = 5) negative deflections of DC potential in the ipsilateral cortex; none were detected in the contralateral cortex. Widespread expression of c-fos mRNA was evident in the ipsilateral cortex, while hsp72 mRNA expression was restricted to the KCl application site. The present results demonstrate that CSD induces tolerance of cortical neurons to ischemia by mechanisms unrelated to hsp72.
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PMID:Spreading depression induces tolerance of cortical neurons to ischemia in rat brain. 767 67

Induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs, and immunoreactivity for HSP70 were investigated in rat hippocampus after transient global ischemia with in situ hybridization and immunohistochemistry. In sham control brain, HSP70 mRNA was scarcely present, while HSC70 mRNA was expressed in most neuronal cells. After 20 min of transient four-vessel occlusion (4VO), ischemia-resistant hippocampal CA3 cells consistently induced HSP70 mRNA along with further HSC70 mRNA. The resistant dentate granule (DG) cells continuously induced HSC70 mRNA even after the great reduction of HSP70 mRNA. In contrast, in ischemia-vulnerable CA1 cells, a relatively lower level of HSC70 mRNA induction than the level of HSP70 mRNA induction was observed. The vulnerable CA1 cells produced a prominent HSP70 immunoreactivity. These results suggest that the vulnerability of the CA1 cells after transient ischemia may not be explained only by the ability of HSP70 induction, but may be related to the imbalance of HSP70 and HSC70 mRNA inductions.
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PMID:Regional difference of HSP70 and HSC70 heat shock mRNA inductions in rat hippocampus after transient global ischemia. 768 48

Recent experiments have shown that neuronal damage following repeated cerebral ischemic insults is more extensive than the damage after a single equivalent period of ischemia. To clarify the mechanism of this cumulative neuronal damage after repeated ischemia, we visualized the localization of heat shock protein-70 (HSP70), a marker of neuronal stress, with immunohistochemistry using a monoclonal antibody. Mongolian gerbils were subjected to three 2-min forebrain ischemic insults spaced at 1-h intervals and to a single 6-min period of ischemia. The animals were killed 24 and 48 h after ischemia. Hippocampal CA1 pyramidal neurons, which are destined to die, showed no HSP70 staining 24 and 48 h after three 2-min ischemic insults, but showed a mild to moderate staining after 6 min of ischemia, suggesting more severe damage after repeated ischemia. CA3 neurons, which are resistant to ischemia, were intensely stained with HSP70 antibody following 6 min of ischemia but was stained only slightly after three 2-min ischemic insults, showing less stress after repeated ischemia. Thus, thresholds for cell damage are obviously different among different cell populations within the hippocampus; the different neuronal populations respond differently to single and repetitive ischemia. The result suggests that cumulative neuronal damage after repeated sublethal ischemic insults is produced by increased susceptibility to subsequent insults when ischemic stress reaches certain thresholds that are different among different neuronal populations.
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PMID:Immunohistochemical visualization of heat shock protein-70 in the gerbil hippocampus following repeated brief cerebral ischemia. 768 12

Myocardial protection and changes in gene expression follow whole body heat stress. Circumstantial evidence suggests that an inducible 70-kD heat shock protein (hsp70i), increased markedly by whole body heat stress, contributes to the protection. Transgenic mouse lines were constructed with a cytomegalovirus enhancer and beta-actin promoter driving rat hsp70i expression in heterozygote animals. Unstressed, transgene positive mice expressed higher levels of myocardial hsp70i than transgene negative mice after whole body heat stress. This high level of expression occurred without apparent detrimental effect. The hearts harvested from transgene positive mice and transgene negative littermates were Langendorff perfused and subjected to 20 min of warm (37 degrees C) zero-flow ischemia and up to 120 min of reflow while contractile recovery and creatine kinase efflux were measured. Myocardial infarction was demarcated by triphenyltetrazolium. In transgene positive compared with transgene negative hearts, the zone of infarction was reduced by 40%, contractile function at 30 min of reflow was doubled, and efflux of creatine kinase was reduced by approximately 50%. Our findings suggest for the first time that increased myocardial hsp70i expression results in protection of the heart against ischemic injury and that the antiischemic properties of hsp70i have possible therapeutic relevance.
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PMID:Overexpression of the rat inducible 70-kD heat stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury. 770 48

The heat shock response is a conserved response to cell injury. We sought to determine if ischemia alone versus events at reperfusion stimulated expression of the major heat shock protein (hsp-72) in a clinically relevant model of global myocardial ischemia in pigs. Pigs were placed on nonpulsatile cardiopulmonary bypass. Serial transmural cardiac biopsies were taken at baseline following 20 min of normothermic global ischemia (induced by crossclamping the aorta) and at 20, 40, and 60 min of reperfusion. Test animals received a bolus and subsequent aortic root infusion of superoxide dismutase (total 7,500 U/kg) beginning just prior to reperfusion. Hsp-72 mRNA abundance was estimated from Northern blots. We found that hsp-72 mRNA was not induced following 20 min of ischemia but accumulated to high levels within 20 min of reperfusion. Intravascular administration of superoxide dismutase at reperfusion eliminated hsp-72 mRNA induction. We conclude that in the postischemic myocardium, hsp-72 gene expression is dependent on superoxide anion generation at reperfusion. In this setting, hsp-72 gene expression may reflect a specific response to oxidative injury rather than a more general response to metabolic stress associated with ischemia.
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PMID:Myocardial heat shock gene expression in pigs is dependent on superoxide anion generated at reperfusion. 774 25

In fibroblasts, serum stimulation has been shown to activate the immediate-early gene 3CH134 encoding a dual specificity protein phosphatase that regulates mitogen-activated protein kinase. We report here that 3CH134 messenger RNA levels increase during recirculation following 30 min forebrain ischemia in the rat brain. In normal rat brains, 3CH134 messenger RNA was found mainly in neurons of the cortex and thalamus. At recirculation periods up to 1 h after 30 min ischemia, 3CH134 messenger RNA increased in neurons and glial cells of all previously ischemic brain regions. After 3 and 6 h recirculation, a prominent increase of 3CH134 messenger RNA was observed in the pyramidal cell layer of all sectors of the hippocampus and the granule cells of the dentate gyrus, whereas in the other brain regions messenger RNA levels returned to control. Up to 6 h of recirculation the spatial induction pattern of 3CH134 was similar to the pattern observed for the immediate-early genes c-fos and c-jun. Within the hippocampus a similar pattern was also observed for the heat shock protein hsp70 messenger RNA. At 12 and 24 h after ischemia, increased levels of 3CH134 messenger RNA persisted in hippocampal neurons; at the same time a delayed increase of 3CH134 messenger RNA was observed in large neurons of the thalamus and in glial cells in damaged regions of the striatum. At later survival periods, 3CH134 messenger RNA returned to control levels. Our study shows that the mitogen-activated protein kinase phosphatase 3CH134 is induced in the brain after a period of global ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transient forebrain ischemia induces an immediate-early gene encoding the mitogen-activated protein kinase phosphatase 3CH134 in the adult rat brain. 775 88

We investigated whether ischemic preconditioning (PC) produced a second window of protection by delayed synthesis of cardioprotective proteins. Anesthetized open-chest rabbits were subjected to 30 min of coronary occlusion and 3 h of reperfusion. PC was elicited by 5 min of ischemia and was separated from sustained ischemia by 5 min, 2 h, or 24 h of reperfusion. Infarct size (% area at risk) was markedly limited by PC with 5 min of reperfusion when compared with controls (13.3 +/- 2.5 vs. 46.8 +/- 7.0%; P < 0.05). This protective effect was lost when the interval between PC and sustained ischemia was extended to 2 h (47.8 +/- 4.8%; P = NS vs. control) and did not reoccur even when it was extended to 24 h (44.2 +/- 6.5%; P = NS vs. sham-operated control). To potentiate induction of heat shock proteins (HSPs), a PC protocol involving four 5-min episodes of ischemia and reperfusion was also used and was separated from sustained ischemia by 24 or 48 h of reperfusion. However, neither of these protocols was protective, and limitation of infarct size was not observed (55.5 +/- 5.9 and 53.4 +/- 6.5% in 24 and 48 h of reperfusion, respectively; P = NS vs. corresponding sham-operated control). Myocardial expression of HSPs was examined using a monoclonal antibody against 72- to 73-kDa HSP in additional rabbits. Immunoreactivity was observed in the myocardium at 24 and 48 h after PC, but not immediately after PC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ischemic preconditioning elevates cardiac stress protein but does not limit infarct size 24 or 48 h later in rabbits. 794 94

The heat shock (HS) response is remarkably conserved during evolution and is evoked under many conditions of stress. There are a number of ways in which this ubiquitous response may be important for the understanding of renal pathophysiology. Ischemia, toxin exposure, and oxidative stress induce this response. Several models of hypertension are associated with increased susceptibility to environmental stress and increased accumulation of heat shock protein mRNA. HSP70 polymorphism has been demonstrated when comparing normotensive and hypertensive rats. Heat shock proteins may play a role in renal diseases through their important involvement in immunological processes. Several observations point to a role of the heat shock response in systemic lupus erythematosus (SLE). Autoantibodies against HSP70 and ubiquitin are found in many patients with this disease. Autoantibodies against ubiquitin and ubiquitinated histone H2A are localized to the kidney glomerular basement membrane of SLE patients with active disease. A better understanding of the HS response may thus provide important insight into renal pathophysiology and may suggest paradigms for therapeutic interventions.
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PMID:Heat shock proteins and the kidney. 804 58

There is compelling, although indirect, evidence that oxygen free radicals, generated during ischemia as well as upon reperfusion and reoxygenation of the ischemic heart, contribute to the reversible ventricular dysfunction characterized as myocardial stunning. Evidence of cell membrane damage as well as depression of sarcoplasmic reticulum and mitochondrial function with resulting calcium overload of the cell may be a result of lipid peroxidation of the cell by free radical products. Radical scavenger enzymes have been shown to greatly reduce the appearance of mRNA of a stress response protein (heat shock protein 71) in a pig heart model of stunning. The potential role for the introduction of antioxidant enzymes or stress protein in the cell is presented as a possible strategy for attenuating free radical damage during postischemic reflow.
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PMID:Oxygen radicals and myocardial stunning. 806 31

Excitatory amino acids (EAAs) are important mediators of ischemic injury in stroke. N-Methyl-D-aspartate (NMDA) receptor antagonists have been shown to be very effective neuroprotective agents in animal models of stroke, but may have unacceptable toxicity for human use. An alternative approach is to inhibit the release of EAAs during stroke. BW1003C87 [5-(2,3,5-trichlorophenyl)-2,4-diaminopyrimidine], a drug that inhibits veratrine-induced release of the EAA glutamate in vitro, was tested in a rat model of proximal middle cerebral artery (MCA) occlusion. BW1003C87 significantly decreased ischemia-induced glutamate release in brain when given either 5 min before or 15 min following permanent MCA occlusion. Pretreated and posttreated rats had smaller infarct volumes and preserved glucose metabolism in the ischemic cortex at 24 h after MCA occlusion. BW1003C87 did not induce heat shock protein in the cingulate or retrosplenial cortex, suggesting that it does not injure neurons in these regions as do NMDA antagonists. These results demonstrate that drugs that inhibit glutamate release in ischemia may be nontoxic and show promise for the treatment of stroke.
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PMID:Limiting ischemic injury by inhibition of excitatory amino acid release. 809 50


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