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

AMPA antagonists have been shown to be remarkably neuroprotective in models of global ischemia, but the data in focal ischemia remain controversial. We, therefore, studied the dose-response characteristics and the time window of efficacy of the AMPA antagonist NBQX in a rat model of permanent focal ischemia. NBQX 40, 60 or 100 mg/kg i.v., substantially reduced infarct size. Neuroprotection was maintained when the initiation of drug administration was withheld for 15, 45 or 90 min after permanent middle cerebral artery occlusion. Furthermore, NBQX did not induce heat shock protein in cingulate cortex, as do some N-methyl-D-aspartate antagonists. Thus, the compound is a potent neuroprotectant in focal ischemia and has an unusually long time window of effectiveness.
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PMID:A dose-response study of neuroprotection using the AMPA antagonist NBQX in rat focal cerebral ischemia. 855 16

In this overview four questions were discussed related to heat shock proteins and myocardial ischemia. Heat shock proteins are chaperones which associate with malfolded proteins and prevent their aggregation into large damaging complexes. In myocardial ischemia, the inducible heat shock protein 70 (hsp70), the mitochondrial heat shock protein 60 and the small 27 heat shock protein increases after 30 minutes of ischemia of the rat heart and subsequent reperfusion. In addition, we describe direct evidence for the protective effect of heat shock proteins against simulated ischemia in H9c2 cells. H9c2 cells are an embryonal rat heart derived permanent cell line which maintains some features of cardiac myocytes. Making stable lines overexpressing the inducible hsp70 we could show that simulated ischemia leads to less injury in H9c2 cells overexpressing the hsp70 transgene. In addition, transgenic mice were constructed in which the rat inducible hsp70 is induced in cardiac myocytes. Submitting such hearts in a Langendorf isolated heart perfusion set-up to 20 minutes of global ischemia and following the contractile recovery of the heart, we found that in transgenic mouse hearts contractile recovery was significantly enhanced. Furthermore in hearts from transgenic mice overexpressing the inducible hsp70, less CK release occurs and infarct size was decreased. In summary, increased expression of the inducible hsp70 exerts a protective effect against the injury induced by myocardial ischemia.
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PMID:Heat shock proteins in myocardial stress. 858 78

The aim was to examine the expression of ubiquitin (Ub), 27 kDa heat shock protein (hsp 27) and hsp 60 mRNA in normal and briefly ischemic and reperfused porcine myocardium. The left anterior descending coronary artery was occluded for two periods of 10 min, separated by 30 min of reperfusion. After the second occlusion the myocardium was reperfused up to 210 min. Tissue from ischemic, ischemic-reperfused and nonischemic regions of the heart were analysed by Northern and slot blot hybridization and nuclear run-on transcription assays employing radiolabelled cDNA probes for Ub, hsp 27 and hsp 60 as well as by Western blot using monoclonal antibodies recognizing Ub protein conjugates and antiserum recognizing hsp 27. Systolic wall thickening was significantly decreased at 30 min reperfusion after both occlusions and remained depressed at longer periods of reperfusion. Using Northern blot hybridizations several mRNAs encoding Ub, 0.9 kb mRNA encoding hsp 27, and 2.2 kb mRNA encoding hsp 60 were detected in sham-operated, nonischemic and ischemic myocardial tissues. Densitometric analysis of Northern and slot blot hybridization signals showed the significant increase of the basal tissue levels of Ub mRNA in stunned regions only during the 30 min of the second reperfusion period. Increased levels of hsp 27 mRNA in stunned tissue were already noted at the first ischemic period and were sustained during the subsequent periods of reperfusion as compared to the control region of the heart. Changes in hsp 60 mRNA tissue levels were not observed during ischemia and subsequent reperfusions. Transcription of the Ub and hsp 27 genes was increased during 30 and 120 min of the second reperfusion period. The transient enhancement of tissue levels of Ub mRNA was associated with the temporary formation of new Ub-protein conjugates. However, the increased synthesis of mRNA encoding hsp 27 was not followed by changes of hsp 27 protein content in the myocardial tissue.
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PMID:[Expression of heat shock proteins in the normal and acutely stunned myocardium]. 858 25

This review focusses on the following issues: how the mammalian heart grows and ages; age-related changes in the mammalian heart before and after imposition of hemodynamic stress; and antiaging modulation in the mammalian heart. The heart and other organs grow and age together in the whole body, and interactions occur between these organs. Therefore, the age-related changes at the molecular and cellular level in the in vivo heart are the summation of the changes of the heart per se and the effects of other organs or tissues on the heart. Furthermore, myocytes grow and age under the influence of age-related changes in other myocytes and other types of cells in the myocardial tissue through autocrine or paracrine mechanisms, because myocytes are exposed to many biologically active substances which are released from those cells. Since hypertension and ischemia are very common hemodynamic events in aged hearts, the characteristics in aged hearts are discussed in terms of responses to hypertension or ischemia. The induction of proto-oncogenes and heat shock protein genes in response to milder hemodynamic stress such as pressure-overload and ischemia is diminished in aged hearts. However, the aged heart can respond to more severe stress to a level similar to that of young-adult hearts. Therefore, the senescent heart is characterized by its attenuated adaptation to hemodynamic stress and by its ability to adapt to limited environmental changes. Several interventions have antiaging effects on the heart at the molecular and cellular level.
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PMID:Age-related changes before and after imposition of hemodynamic stress in the mammalian heart. 863 97

Heat shock proteins are proposed to limit injury resulting from diverse environmental stresses, but direct metabolic evidence for such a cytoprotective function in vertebrates has been largely limited to studies of cultured cells. We generated lines of transgenic mice to express human 70-kDa heat shock protein constitutively in the myocardium. Hearts isolated from these animals demonstrated enhanced recovery of high energy phosphate stores and correction of metabolic acidosis following brief periods of global ischemia sufficient to induce sustained abnormalities of these variables in hearts from nontransgenic littermates. These data demonstrate a direct cardioprotective effect of 70-kDa heat shock protein to enhance postischemic recovery of the intact heart.
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PMID:Cardioprotective effects of 70-kDa heat shock protein in transgenic mice. 863 74

The purpose of this study was to define the differences in heat shock protein (hsp)70, albumin, alpha(-1)-acid glycoprotein (AGP), and CCAAT enhancer binding proteins (C/EBP) alpha and beta mRNA between hepatic ischemia and reperfusion, and to begin to explore C/EBP protein production. These genes have been found important in the hepatic response to lipopolysaccharide and inflammation. In two experiments, Sprague-Dawley rats underwent temporary occlusion of the median and left hepatic lobe vasculature. The first experiment included a single sham-operated group and ligation of the right hepatic lobes during reperfusion. It compared 30 and 60 min ischemia to 2 h reperfusion. The second experiment included a sham-operated group for every time point, and the right hepatic lobes were not ligated during reperfusion; a 30-min ischemia group was compared to 2-, 5-, and 24-h reperfusion groups. Total RNA from the ischemic lobes was analyzed by Northern hybridization for hsp70, albumin, AGP, and C/EBPalpha and beta. C/EBPalpha and beta proteins were compared by Western blotting. Differences in experimental design played an important role in interpretation of results. hsp70 mRNA began to increase during ischemia. Albumin mRNA remained constant during ischemia and reperfusion. The ischemic hepatocyte nucleus is not quiescent and retains the ability to upregulate certain genes, e.g., hsp70. Changes in mRNA in response to hepatic ischemia/reperfusion occur rapidly. Hepatic ischemia/reperfusion does not recapitulate the classic acute phase response; albumin is not down regulated during reperfusion.
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PMID:Early gene response to hepatic ischemia reperfusion. 866 Nov 80

Sublethal endotoxemia attenuates cardiac functional injury from global ischemia but it is unknown whether endotoxemia can protect myocardium against infarction. Furthermore, increases in myocardial catalase and heat shock protein (HSP) following endotoxemia have been associated with cardiac ischemic protection. We therefore hypothesized that a 72-hr pretreatment with endotoxin (ETX) would reduce myocardial tissue necrosis in association with augmented catalase activity and stress protein expression. Rabbits were treated with normal saline or lipopolysaccharide (Salmonella typhimurium) at 10, 5, and 1 microgram/kg doses. Three days after saline or ETX injection they were subjected to 45 min of coronary artery occlusion followed by 3 hr of reperfusion. Area of necrosis (tetrazolium staining) was normalized to anatomic risk zone size (Evans blue staining). Catalase activity was measured by a standard assay and HSP 72 was assessed by immunohistochemistry. During regional ischemia and reperfusion there were no differences in heart rate or mean arterial blood pressure between groups. ETX treated rabbits had the same risk zone size as controls. Infarct size was reduced in the ETX treated rabbits at the 10 and 5 microgram/kg doses compared with control rabbits (17.5 +/- 1.5% and 22.2 +/- 3.1% vs 45.3 +/- 2.5%; P < 0.05) but no protective effect was observed at the 1.0 micrograms/kg dose (38.0 +/- 4.6%; P > 0.05 vs control). Catalase activity was not different between control and ETX (5 microgram/kg) treated groups (997.8 +/- 59.1 U/g vs 1099.6 +/- 69.3 U/g myocardium; P > 0.05) but endotoxin induced expression of myocardial HSP 72. We conclude that a single challenge with endotoxin can induce delayed myocardial protection against infarction in vivo. This delayed cardioprotective response involves enhanced stress protein expression without changes in myocellular catalase activity.
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PMID:A single endotoxin challenge induces delayed myocardial protection against infarcation. 866 Nov 96

Current experimental research on subarachnoid hemorrhage (SAH) has been limited by the lack of a small-animal model that physiologically resembles SAH and consistently demonstrates acute and delayed cellular injury. Recently, a model for inducing SAH by endovascular perforation of the internal carotid artery has been developed in the rat. This model physiologically resembles SAH. However, little histological data detailing cellular injury after SAH are available in this or other models. Using immunocytochemistry, the authors investigated the induction of the 70-kD heat shock protein, HSP70, a sensitive marker for cellular stress or injury in the brain, 1 and 5 days following endovascular SAH. The authors also used the conventional histological techniques of cresyl violet and hematoxylin and eosin staining to investigate cellular damage 1 and 5 days after the endovascular SAH. One day following the SAH, HSP70 was induced in all six animals examined in multiple anatomical regions, including the basal forebrain, thalamus, neocortex, striatum, and hippocampus. This HSP70 induction was observed in multiple vascular distributions bilaterally. Immunostaining with HSP70 occurred primarily in neurons but also was observed in glia and endothelium. Five days after the SAH, a similar but more intense pattern of HSP70 immunostaining was observed in all eight animals examined. Specifically, HSP70 immunoreactivity was observed in at least one region of the hippocampus more often at 5 days (six of eight animals) than at 1 day (one of six animals, p < 0.05, one-tailed Fisher's exact test). No HSP70 immunostaining was observed in control animals at 1 day or at 5 days. Conventional histology demonstrated foci of ischemic neuronal damage and cellular necrosis; however, HSP70 immunocytochemistry detailed cellular injury far better than conventional histology in all animals tested at both 1 day and 5 days. Our results demonstrate that HSP70 is induced in multiple regions and cell types 1 day and 5 days following endovascular SAH. Because ischemia is a known inducer of stress genes, the authors propose that acute and delayed ischemia are the processes responsible for the induction of HSP70 that was observed at 1 day and 5 days, respectively. Investigation of HSP70 induction following endovascular SAH may also serve as the basis for a new, inexpensive animal model to assess potential therapeutic interventions.
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PMID:Induction of HSP70 in rat brain following subarachnoid hemorrhage produced by endovascular perforation. 898 6

The purpose of this study was to evaluate the protective effect of a new endotoxin analogue, monophosphoryl lipid A (MLA) in a rabbit model of myocardial ischemia/reperfusion and to show if this protection was mediated via synthesis of 70 kDa heat shock protein (HSP 70). Three groups of New Zealand White rabbits underwent 30 min coronary occlusion, followed by 4 hours reperfusion. First group of rabbits (n = 6) were treated with 0.35 ml vehicle (40 % propylene glycol, 10 % ethanol in water). The second and third group of rabbits (n = 6-8) were treated with MLA (35 micrograms/kg, i.v.) 12 and 24 hours prior to ischemia and reperfusion. MLA treatment either 12 or 24 h prior to ischemia/reperfusion demonstrated significantly reduced infarct size (12.5 +/- 1.7 and 14.7 +/- 2.1% for 12 and 24 h) when compared with vehicle control (40.4 +/- 8.6%, mean +/- S.E.M, p < 0.05). No significant differences in the infarct size was observed between the 12 and 24 h MLA treated groups. The area at risk was not significantly different between the three groups. Baseline values of heart rate, systolic and diastolic blood pressure were not significantly different between the control and MLA treated groups. However, the systolic as well as diastolic blood pressure during reperfusion were significantly lower in rabbits treated with MLA. Western blot analysis of the protein extracts of the hearts (n = 2/group) demonstrated no increase in the expression of the inducible form of HSP 70 following treatment with MLA. We conclude that MLA has significant anti-infarct effect in rabbit which is not mediated by the cardioprotective protein HSP 70. The anti-infarct effect of this drug is superior to the reported protective effects of delayed ischemic or heat stress preconditioning. We hypothesize that the pharmacologic preconditioning afforded by MLA is accomplished via a unique pathway that bypasses the usual intracellular signaling pathways which lead to the myocardial protection with the expression of heat shock proteins.
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PMID:Monophosphoryl lipid A induces pharmacologic 'preconditioning' in rabbit hearts without concomitant expression of 70-kDa heat shock protein. 870 70

Changes in gene expression in the brain in response to adverse conditions, such as ischemia or excitotoxin exposure, may be part of the injury process or represent an adaptive response which may be protective during subsequent stressful events. In this review we have considered the regulation, functions and potential relationships to the pathophysiology of ischemia of several major groups of stress-induced genes, including those of the M(r) 27,000, 32,000 (heme oxygenase), 70,000 and 90,000 heat shock protein families, the glucose-regulated proteins, glucose transporters and ubiquitin. Patterns of gene expression in several injury models, including focal and global ischemia, excitotoxin/ seizure-related injury and hyperthermia are reviewed. In vitro expression studies and the phenomenon of ischemic tolerance are also discussed. It is concluded that stress gene expression provides a useful marker of cellular injury, and that disjunction of mRNA and protein expression may be indicative of imminent death in cells which survive the initial insult. Though other stress proteins may play a role, it seems unlikely that neuronal hsp70 expression is a major contributor to ischemic tolerance.
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PMID:The stress gene response in brain. 872 84


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