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

Cerebral ischemia induces the expression of a number of proteins that may have an important influence on cellular injury. The purpose of this study was to compare the regional effects of hypoxia-ischemia on the expression of the proto-oncogene, c-fos, and the heat shock protein-70 (HSP-70) gene in developing brain. Unilateral hypoxia-ischemia was produced in the brain of immature rats (7, 15, and 23 days after birth) using a combination of carotid artery ligation and systemic hypoxia (8% O2). After recovery for 2 and 24 h, the regional expression of c-fos and HSP-70 mRNA was determined using in situ hybridization. Littermates were permitted to recover for 1 week for assessment of histologic injury. Hypoxia-ischemia increased the expression of both c-fos and HSP-70 mRNA, but the topography of expression varied with the age of the animal as well as the mRNA species. In the 7-day-old group, expression of c-fos at 2 h increased in multiple regions of the ipsilateral hemisphere in nearly one-half of the animals, while HSP-70 mRNA was not expressed until 24 h and, then, predominantly in the hippocampus. In 15- and 23-day-old rats, expression of c-fos was increased at 2 h in the entorhinal cortex and in the dendritic field of the upper blade of the hippocampal dentate gyrus, while HSP-70 mRNA was prominently expressed in neocortex and the cell layers of the hippocampus. Interestingly, the strong expression of HSP-70 mRNA in dentate granule cells did not occur in the innermost layer of cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional expression of c-fos and heat shock protein-70 mRNA following hypoxia-ischemia in immature rat brain. 140 Jun 53

In situ hybridization was used to estimate regional levels of heat shock protein-70 (HSP-70) mRNA and c-fos mRNA in two related models of focal cerebral ischemia. In the first model, permanent occlusion of the distal middle cerebral artery (MCA) alone caused a patchy increase in HSP-70 mRNA by 1 h in the central zone of the MCA territory of the ipsilateral neocortex. Tissue levels of HSP-70 mRNA continued to increase for several hours and remained elevated at 24 h. In contrast to the focal expression of HSP-70, c-fos mRNA was increased throughout the ipsilateral cerebral cortex by 15 min and remained elevated for least 3 h. The wide distribution of c-fos expression suggests it may have been caused by spreading depression. In the second model, severe focal ischemia was produced with a combination of transient (1-h) bilateral carotid artery occlusion and permanent MCA occlusion. Combined occlusion for 1 h without reperfusion caused expression of HSP-70 mRNA only in regions adjacent to the central zone of the MCA territory of the neocortex. However, reperfusion of the carotids for 2 h generated intense expression of HSP-70 mRNA throughout most of the ipsilateral cerebral cortex, white matter, striatum, and hippocampus. The wide-spread increase in HSP-70 mRNA suggests that reperfusion triggered expression in all previously ischemic regions. However, at 24 h of reperfusion, increased levels of HSP-70 mRNA were restricted primarily to the ischemic core of the neocortex. These results suggest that expression of HSP-70 mRNA is prolonged in regions undergoing injury, but is transient in surrounding regions that recover.
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PMID:Regional expression of heat shock protein-70 mRNA and c-fos mRNA following focal ischemia in rat brain. 154 93

We investigated the effects of mild and non-lethal ischemic insult on neuronal death following subsequent lethal ischemic stress in various brain regions, using a gerbil model of bilateral cerebral ischemia. Single 10-min ischemia consistently caused neuronal damage in the hippocampal CA1, CA2, CA3 and CA4, layer III/IV of the cerebral cortex, dorsolateral part of the caudoputamen and ventrolateral part of the thalamus. On the other hand, in double ischemia groups, 2-min ischemic insult 2 days before 10-min ischemia exhibited significant protection in the CA1 and CA3 of the hippocampus, the cerebral cortex, the caudoputamen and the thalamus. Five-min ischemic insult 2 days before 10-min ischemia also showed protective effect in the same areas as those of 2-min ischemia except for the CA1 region of the hippocampus, while 1-min ischemic insult exhibited no protective effect in any brain regions. In the immunoblot analysis, both 2- and 5-min ischemia caused increased synthesis of heat shock protein 72 (HSP 72) in the hippocampus, but 1-min ischemia did not. The present study demonstrated that the 'ischemic tolerance' phenomenon was widely found in the brain and also suggested that ischemic treatment severe enough to cause HSP 72 synthesis might be needed for induction of 'ischemic tolerance'.
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PMID:'Ischemic tolerance' phenomenon detected in various brain regions. 180 39

Focal cerebral ischemia in the adult rat produces induction of 72-kDa heat shock protein (HSP-72) in neurons, glia and endothelial cells. Double antigen immunocytochemistry was carried out to find out whether microglial cells express HSP-72 following 1-h middle cerebral artery (MCA) occlusion. A monoclonal antibody against the CR3 complement receptor (OX-42) specific for microglia was used followed by a monoclonal antibody against HSP-72. Co-localization of these antibodies was seen in cells of the ipsilateral corpus callosum and striatum at 3 h following 1-h MCA occlusion, and in the ipsilateral striatal penumbra, corpus callosum and cortex at 8 h. Results demonstrate that stellate microglial cells show an early response to 1-h MCA occlusion by expressing inducible HSP-72, thus suggesting that microglial cells are sensitive to the ischemic insult.
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PMID:Early 72-kDa heat shock protein induction in microglial cells following focal ischemia in the rat brain. 771 11

Immunohistochemical changes of heat shock protein 70 (HSP 70) and glial fibrillary acidic protein (GFAP) were investigated in the gerbil hippocampus 1 h-7 days after 10 min of cerebral ischemia. Transient cerebral ischemia caused HSP 70 expression in GFAP-positive astrocytes in a delayed fashion, as compared with a rapid induction in vulnerable neurons such as hilar neurons. The present results may offer clues to elucidate the mechanisms of ischemic neuronal damage.
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PMID:Induction of heat shock protein 70 and glial fibrillary acidic protein in the postischemic gerbil hippocampus. 789 3

We report here the time-dependent expression of several classes of HSP mRNAs following focal cerebral ischemia in rats. HSP70, GRP78, HSP27, HSP90 and HSP47 have been reported to possess distinct functions under normal and/or stress conditions. These different classes of HSP mRNAs were differentially induced by ischemia, as determined by Northern blot analysis. Messenger RNAs of the HSP70 family proteins were induced within 4 h after ischemia and then rapidly decreased, whereas HSP27 and HSP47 mRNAs reached a maximum level of expression at 24 h and 48 h after ischemic treatment, respectively. In situ hybridization showed that the expression of inducible HSP70 mRNA was observed predominantly in regions adjacent to the ischemic core except during the early periods of ischemia. HSP27 mRNA was expressed over a broad area of the ipsilateral cerebral neocortex except for the ischemic center 24 h after ischemia. The unique induction kinetics for each HSP mRNA species may reflect their distinct roles in the brain during various physiological stresses. We will also discuss that stress proteins may be involved in the central nervous system after ischemia in two important aspects: early protection against stress and restoration of damaged lesions in the brain at later stages after ischemia.
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PMID:Differential induction of mRNA species encoding several classes of stress proteins following focal cerebral ischemia in rats. 795 88

Stroke, an age-related disorder involving degeneration of neurons resulting from cerebral ischemia, is a major cause of disability and mortality. Although dietary restriction (DR) extends lifespan and reduces levels of cellular oxidative stress in several different organ systems including the brain, the impact of DR on ischemic brain injury is unknown. We report that maintenance of adult rats on a DR regimen resulted in reduced brain damage and improved behavioral outcome in a middle cerebral artery occlusion-reperfusion (MCAO-R) stroke model. Administration of 2-deoxyglucose (2-DG), a nonmetabolizable analogue of glucose, to rats fed ad libitum resulted in reduced ischemic brain damage and improved behavioral outcome following MCAO-R. 2-DG protected cultured hippocampal neurons against chemical hypoxia, demonstrating a direct protective action on neurons. DR and 2-DG administration resulted in an increase in the level of the stress protein heat-shock protein 70 (HSP-70) in striatal cells in vivo, and 2-DG treatment induced HSP-70 in cultured neurons suggesting involvement of a preconditioning stress response in the neuroprotective actions of DR and 2-DG. The neuroprotective effect of DR and 2-DG in this focal cerebral ischemia model suggests that outcome following stroke may be improved in individuals who follow a regimen of reduced food intake.
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PMID:Dietary restriction and 2-deoxyglucose administration reduce focal ischemic brain damage and improve behavioral outcome: evidence for a preconditioning mechanism. 1046 54

1. The present study was designed to examine the regional expression of HSP72/73 protein after a 7.5-min period of cerebral ischemia and to compare the distribution of HSP neurons with the localization of irreversible neuronal degeneration as analyzed by silver impregnation technique. 2. During 6-24 hr after cerebral ischemia clear-cut neuronal argyrophilia developed in several brain regions including the hippocampal hilus, nucleus reticularis thalami, and colliculi inferiores. With the exception of the hippocampal hilus, the structures which showed silver impregnability were HSP72 negative at 6-24 hr. 3. Despite the clear HSP72 expression seen in hippocampal CA1 neurons, a significant loss of these neurons was seen at 7 days after ischemia. 4. These data show that in some structures the presence of HSP72 is indicative of higher resistance of these neurons to ischemia-induced degeneration, however, the process of delayed neuronal degeneration appears to be independent of the accelerated synthesis of HSP72 seen during the early period of reflow.
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PMID:Time course of brain neuronal degeneration and heat shock protein (72) expression following neck tourniquet-induced cerebral ischemia in the rat. 1078 34

Global cerebral ischemia, with or without preconditioning, leads to an increase in heat shock protein 27 (HSP27) immunocontent and alterations in HSP27 phosphorylation in CA1 and dentate gyrus areas of the hippocampus. We studied different times of reperfusion (1, 4, 7, 14, 21 and 30 days) using 2 min, 10 min or 2+10 min of ischemia. The results showed an increase in HSP27 immunocontent of about 300% after 10 min of ischemia in CA1 and dentate gyrus. CA1, a hippocampal vulnerable area, showed an increase in HSP27 phosphorylation, parallel with immunocontent. In dentate gyrus, a resistant area, the increase in HSP phosphorylation was lower than immunocontent. After preconditioned ischemia (2+10 min), when CA1 neurons are protected to a lethal, 10 min insult, we observed an increase in HSP immunocontent and a decrease in phosphorylation in both regions of the hippocampus, suggesting that, when there is no neuronal death, HSP27 in a vulnerable area responds similarly to the resistant area.When dephosphorylated, HSP27 acts as a chaperone, protecting other proteins from denaturation. As it is markedly expressed in astrocytes, we suggest that HSP27 could be protecting hippocampal astrocytes, which could then be helping neurons to resist to the insult, maintaining tissue normal homeostasis.
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PMID:Effects of global cerebral ischemia and preconditioning on heat shock protein 27 immunocontent and phosphorylation in rat hippocampus. 1174 45

Heat shock protein (HSP70), a member of the 70 kDa HSP superfamily, has been widely implicated in the cellular stress response to numerous insults. HSP70 may be a significant factor in cell survival following stresses such as cerebral ischaemia. The precise mechanisms by which HSP70 facilitates cell survival remain unclear. The aim of this study was to ascertain whether any differences in local cerebral glucose utilization (LCGU) existed between transgenic mice overexpressing HSP70 (HSP70 Tg) and wild- type littermate (WT) mice. LCGU was assessed using (14)C-2-deoxyglucose in HSP70 Tg and WT mice under basal conditions (intraperitoneal injection of saline) and during metabolic activation produced by NMDA receptor blockade (intraperitoneal injection of dizocilpine, 1 mg/kg). No significant alterations in LCGU were observed between saline injected HSP70 Tg and WT mice in any of the 35 brain regions analyzed. Dizocilpine injection produced significant heterogeneous alterations in LCGU in HSP70 Tg mice (24 of 35 brain regions) and in WT mice (22 of 35 brain regions) compared with saline injected mice. The distribution of altered LCGU produced by dizocilpine was similar in HSP70 Tg and WT mice. However in five brain regions, dizocilpine injected HSP70 Tg mice displayed significantly altered LCGU compared to dizocilpine injected WT mice (anterior thalamic nucleus +27%, dorsal CA1 stratum lacunosum molecularae +22%, dorsal CA1 stratum oriens + 14%, superior olivary body -26%, and the nucleus of the lateral lemniscus -16%). These data highlight that while overexpression of HSP70 transgene does not significantly alter LCGU in the basal state, mice overexpressing the HSP70 transgene respond differently to metabolic stress produced by NMDA receptor blockade in some important brain regions.
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PMID:Cerebral glucose utilization in transgenic mice overexpressing heat shock protein 70 is altered by dizocilpine. 1191 53


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