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

To study the roles of bFGF and its receptor in the process of neuronal cell death and the wound repair response, we induced 10 min of transient global cerebral ischemia in rats and measured changes in expression of both bFGF and the FGF receptor, flg. CA1 pyramidal cells are selectively vulnerable to ischemia and die one to 3 days after 10 min of ischemia. In these cells, bFGF mRNA was induced by 6 hours, reached a maximal level by 24 h after ischemia, and subsequently decreased. Message for the FGF receptor, flg, was present in the pyramidal cells layer, and vanished almost completely in parallel with neuronal death. In the granule cell layer of dentate gyrus, the expression of bFGF mRNA increased more rapidly. It was maximal by 6 h and returned to the basal level by 3 days. In the hilus of the dentate gyrus, bFGF expression was maximal at 24 h and returned to control levels by 3 days. Despite the rapid changes in expression of bFGF mRNA, there was no significant change of bFGF immunoreactivity in either the CA1 pyramidal cell layer or in the granule cell layer of dentate gyrus within 3 days after ischemia. The apparent failure of the message to be efficiently translated supports the idea that translation is impaired under conditions where ischemia leads to delayed neuronal cell death. Expression of bFGF mRNA, FGFR mRNA and bFGF immunoreactivity increased dramatically in a broad area of CA1 subfield from 7 days until 30 days after ischemia because of increased expression by reactive glial cells. We suggest that these rapid and complex changes in the expression of bFGF mRNA and bFGF protein may be part of a coordinated response to ischemic injury that is designed to minimize the severity of neuron death.
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PMID:Transient global ischemia induces dynamic changes in the expression of bFGF and the FGF receptor. 801 96

Recently, we demonstrated that transient forebrain ischemia in rats leads to an early and strong induction of basic fibroblast growth factor (bFGF) synthesis in astrocytes in the injured brain regions. In this study, in order to clarify the targets of such raised endogenous bFGF levels, the messenger RNA (mRNA) expression of its receptors (flg and bek) in the hippocampus following transient forebrain ischemia induced by four-vessel occlusion for 20 min was investigated using an in situ hybridization technique. Transient forebrain ischemia induced an increase in the number of flg mRNA-positive cells from an early stage (24 h after ischemia) in the hippocampal CA1 subfield where delayed neuronal death occurred later (48-72 h after ischemia). This increase became more marked with the progression of neuronal death and was still evident in the same area 30 days later. The time course of the appearance and distribution pattern of flg mRNA-positive cells in the CA1 subfield were quite similar to those of bFGF mRNA-positive cells. On the other hand, in situ hybridization for bek mRNA showed only slight and transient (observed 72 h and 5 days after ischemia) increases in the number of mRNA-positive cells in the CA1 subfield following ischemia. The use of in situ hybridization and glial fibrillary acidic protein immunohistochemistry in combination demonstrated that the cells in the CA1 subfield that exhibited ischemia-induced flg or bek mRNA expression were astrocytes. These data indicate that transient forebrain ischemia induces upregulation of fibroblast growth factor-receptor expression, accompanied by increased bFGF expression in astrocytes, and suggest that the increased astrocytic bFGF levels in injured brain regions act on the astrocytes via autocrine systems and are involved in the development and maintenance of astrocytosis.
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PMID:Upregulation of fibroblast growth factor-receptor messenger RNA expression in rat brain following transient forebrain ischemia. 815 41

In the present study the neuroprotective effect of mild hypothermia (decrease of temperature from 37degreesC to 33degreesC) during and after transient ischemia in brain tissue at different stages of development was tested in vitro by measuring energy metabolism, glutamate release and protein biosynthesis rate (PSR) in hippocampal slices. Slices were taken from immature (E40) and mature (E60) guinea pig fetuses and adult guinea pigs. The slices were exposed to ischemia-like conditions (oxygen/glucose deprivation, OGD) for periods of between 10 to 40 min followed by a 2-h or 12-h recovery phase. During OGD, mild hypothermia slowed down the depletion of energy stores only in slices from immature fetuses, but had no effect on slices prepared from mature fetuses and adult animals. Hypothermia also reduced glutamate release significantly during oxygen/glucose deprivation. Lowering temperature to 33degreesC had no effect on energy metabolism and only a minor effect on PSR of slices from mature fetuses and adult animals subjected to 2 h of recovery. However, 12 h after OGD PSR was markedly improved by mild hypothermia in slices from mature animals and in slices from adults that had been exposed to OGD for only 20 or 30 min. The inhibition of PSR was more severe in the slices from adults than in those from mature fetuses subjected to the same duration of OGD. Age- and temperature-related differences in glutamate release during OGD did not fully agree with corresponding disparities in the values for PSR obtained 12 h after OGD. These results indicate that the neuroprotective effect of mild hypothermia was not mediated by a temperature-dependent retardation of the depletion of energy stores during OGD. Age-related disparities in the vulnerability of the brain to ischemia and the neuroprotective efficiency of mild hypothermia appear to be only partially reflected by the varying levels of glutamate release during ischemia but best reflected by the extent of PSR inhibition. It is concluded that mild hypothermia may be a suitable therapeutical intervention for the suppression of hypoxic-ischemic cell damage during birth.
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PMID:Effect of mild hypothermia during and after transient in vitro ischemia on metabolic disturbances in hippocampal slices at different stages of development 947 92

In the present study the neuroprotective effect of mild hypothermia (decrease of temperature from 37 degrees C to 33 degrees C) during and after transient ischemia in brain tissue at different stages of development was tested in vitro by measuring energy metabolism, glutamate release and protein biosynthesis rate (PSR) in hippocampal slices. Slices were taken from immature (E40) and mature (E60) guinea pig fetuses and adult guinea pigs. The slices were exposed to ischemia-like conditions (oxygen/glucose deprivation, OGD) for periods of between 10 to 40 min followed by a 2-h or 12-h recovery phase. During OGD, mild hypothermia slowed down the depletion of energy stores only in slices from immature fetuses, but had no effect on slices prepared from mature fetuses and adult animals. Hypothermia also reduced glutamate release significantly during oxygen/glucose deprivation. Lowering temperature to 33 degrees C had no effect on energy metabolism and only a minor effect on PSR of slices from mature fetuses and adult animals subjected to 2 h of recovery. However, 12 h after OGD PSR was markedly improved by mild hypothermia in slices from mature animals and in slices from adults that had been exposed to OGD for only 20 or 30 min. The inhibition of PSR was more severe in the slices from adults than in those from mature fetuses subjected to the same duration of OGD. Age- and temperature-related differences in glutamate release during OGD did not fully agree with corresponding disparities in the values for PSR obtained 12 h after OGD. These results indicate that the neuroprotective effect of mild hypothermia was not mediated by a temperature-dependent retardation of the depletion of energy stores during OGD. Age-related disparities in the vulnerability of the brain to ischemia and the neuroprotective efficiency of mild hypothermia appear to be only partially reflected by the varying levels of glutamate release during ischemia but best reflected by the extent of PSR inhibition. It is concluded that mild hypothermia may be a suitable therapeutical intervention for the suppression of hypoxic-ischemic cell damage during birth.
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PMID:Effect of mild hypothermia during and after transient in vitro ischemia on metabolic disturbances in hippocampal slices at different stages of development. 949 81

We monitored survival of Purkinje cells in rat cerebellar slices to test the hypothesis that isoflurane preconditioning reduces ischemia-induced neuronal death. Preconditioning the brain slices with isoflurane, a volatile anesthetic commonly used in clinical practice, at 1-4% for 15 min at 37 degrees C significantly decreased Purkinje cell injury and death caused by a 20-min ischemia (simulated by oxygen-glucose deprivation, OGD). The effective concentration for half of the maximal effect (EC(50)) for this isoflurane preconditioning-induced neuroprotection was 1.17+/-0.31% and the maximal protective effects were achieved at 3% or higher concentrations of isoflurane. In addition, preconditioning the cells with isoflurane for 15-30 min was needed for the preconditioning to be maximally protective. Although farnesyl protein transferase inhibitor III blocked the protective effects of OGD preconditioning (a 3-min OGD 15 min before the 20-min OGD), this inhibitor did not affect the neuroprotection induced by isoflurane preconditioning. While DL-threo-beta-hydroxyaspartic acid (THA), a specific glutamate transporter inhibitor, did not change basal OGD-induced cell death rate, THA blocked the neuroprotection induced by isoflurane preconditioning but not by OGD preconditioning. Glybenclamide, a K(ATP) channel inhibitor, did not block the neuroprotection induced by either isoflurane or OGD preconditioning. Our results suggest that isoflurane preconditioning is neuroprotective. The isoflurane concentrations and times needed for the preconditioning to be neuroprotective are clinically relevant. The mechanisms of this protection seem to involve modulation of glutamate transporter activity.
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PMID:Isoflurane preconditioning reduces purkinje cell death in an in vitro model of rat cerebellar ischemia. 1267 41

Thrombin plays a role in cerebral ischemia as rats subjected to focal cerebral ischemia were protected by the intracerebral injection of hirudin, a selective thrombin inhibitor. To separate the roles of thrombin in cell death and in coagulation, we have used an in vitro approach to test the effect of hirudin and of protease nexin-1 (PN-1), a cerebral thrombin inhibitor, on neuronal ischemia. Rat organotypic hippocampal slice cultures were subjected to oxygen (5%) and glucose (1 mmol/L) deprivation (OGD) during 30 min. Hirudin or PN-1 administered after OGD significantly prevented neuronal death in the CA1 region. After 24 h, there was a marked increase in thrombin immunoreactivity on Western blots. Thrombin therefore contributes to ischemic damage in neural tissue in vitro.
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PMID:Thrombin in ischemic neuronal death. 1642 45

Hemorrhagic transformation upon reperfusion therapy has focused attention on ischemia-induced endothelial dysfunction. This study examined whether hyperglycemia may induce hemorrhagic transformation by enhancing endothelial mitochondrial damage during ischemia and whether preconditioning (PC) stimuli may limit ischemia-induced endothelial damage. In vivo, rats received 2.8 M D-glucose or arabinose (1 ml/100 g; i.p.) prior to undergoing two hours of middle cerebral artery occlusion and transcardiac fixation for electron microscopy. In vitro, brain endothelial cells were exposed to a PC impulse (short-term oxygen glucose deprivation; OGD) prior to an injurious event (5 hours OGD). Endothelial injury was assessed by measuring lactate dehydrogenase release. Hyperglycemia during cerebral ischemia resulted in marked changes in endothelial morphology and mitochondrial swelling. Thus, in the ischemic hemisphere, there was no evidence of endothelial mitochondrial swelling in normoglycemic rats (mean profile width 0.22 +/- 0.04 vs. 0.17 +/- 0.01 microm in contralateral hemisphere) but there was marked swelling in hyperglycemic rats (0.44 +/- 0.02 microm). In vitro, cells preconditioned with one hour of OGD one day prior to 5 hours of OGD, showed reduced lactate dehydrogenase release (p < 0.05). In conclusion, hyperglycemia may have specific adverse effects on endothelial cell mitochondria during ischemia. Preventing those effects may help to ameliorate blood-brain barrier disruption on reperfusion. Insights into how to prevent endothelial injury may come from determining the mechanisms involved in endothelial preconditioning.
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PMID:Ischemia-induced endothelial cell dysfunction. 1646 89

The study aims to explore the protection mechanism of exogenous basic fibroblast growth factor (exo-bFGF) in brain ischemia. The first part of experiment was to determine the optimal time window for the permeation of exo-bFGF through damaged blood-brain barrier in rats with permanently occluded middle cerebral arteries. 125I labeled bFGF was administered to the rats through the caudal vein. The level of gamma-rays of 125I-bFGF in the ischemic brain were found to increase at 2 h and a high level was maintained for 14 days. The morphology of the basement membrane of capillaries was observed using anti-blood-brain barrier basement membrane glycoprotein immunohistochemistry. The normal continuous linear or ribbon-like immunostain of the basement membrane became granular at 0.5 h, gradually faint and finally negative. The newly formed capillaries at the edge of the infarct still showed a negative stain after 14 days. The result suggested the optimal time window of exo-bFGF began 2 h after insult. The second part of experiment was to observe the dynamic expression of early growth response protein (Egr-1), endogenous basic fibroblast growth factor (endo-bFGF) and bFGF receptor (bFGFR) using immunohistochemistry after exo-bFGF is administered to brain. Egr-1 was more significantly enhanced in the exo-bFGF-used group than in the control group. Endo-bFGF increased gradually, reaching its peak at 7 days in the control group, while in experiment group, the endo-bFGF expression showed its first peak at 6 h, indicating that exo-bFGF could induce earlier and stronger expression of endo-bFGF. The bFGFR-group presented an early expression, reaching its maximal level at 3 h, and declining at 6 h. There were no difference in expression of bFGFR between the two groups. The infarct areas reduced from 17% to 24% in the different time intervals. The results suggested that in exo-bFGF enhanced Egr-1 protein. Egr-1 in turn might play an important role in up-regulating the expression of endo-bFGF which overlapped with the expression of bFGFR to ensure the combination of ligand and receptor to protect against brain ischemia.
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PMID:Permeability of injured blood brain barrier for exogenous bFGF and protection mechanism of bFGF in rat brain ischemia. 1677 Nov 84

We have shown that exposure of neurons to opioid immediately before ischemia induces ischemia tolerance. This phenomenon is called acute opioid preconditioning. In this study, we test the hypothesis that opioids induce delayed neuropreconditioning (from hours to days after opioid exposure). Exposure to morphine, an agonist for delta-, mu-, and kappa-opioid receptors, or Tan-67, a selective delta1-receptor agonist, for 30 minutes at 24 hours before a 35-minute oxygen-glucose deprivation (OGD, to simulate ischemia in vitro) dose-dependently reduced the OGD-induced neuronal death in the CA1 region of the rat organotypic hippocampal slice cultures. The morphine preconditioning-induced neuroprotection was inhibited by beta-funaltrexamine, a mu-opioid receptor antagonist, but not by 7-benzylidenenaltrexone, a delta1-receptor antagonist, or nor-binaltorphimine, a kappa-receptor antagonist. The Tan-67 preconditioning-induced neuroprotection was inhibited by 7-benzylidenenaltrexone. The combination of morphine and Tan-67 did not induce a better preconditioning effect than did morphine or Tan-67 alone. Application of morphine and Tan-67 at 24 hours before permanent right middle cerebral arterial occlusion reduced brain infarct volume and improved neurologic functional outcome assessed 24 hours after the occlusion in adult male rats. These results suggest that morphine and Tan-67 induce a delayed preconditioning effect in the brain under in vivo and in vitro conditions. Whereas the delayed phase of morphine preconditioning may involve mu-opioid receptors, Tan-67 preconditioning may be mediated by delta1-opioid receptors. Morphine and Tan-67 may activate a shared intracellular signaling pathway to induce the delayed preconditioning effects in the brain.
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PMID:Opioid preconditioning induces opioid receptor-dependent delayed neuroprotection against ischemia in rats. 1702 99

Oxidative stress is central to ischemia-reperfusion injury. The role of the endoplasmic reticulum (ER) in this process is uncertain. In ER signaling, PERK-Nrf2 and Ire-CHOP are two pathways that determine cell fate under stress. PERK-Nrf2 up-regulates antioxidant enzyme expression whereas Ire-CHOP promotes apoptosis. We have identified a novel pathway in ER stress-induced apoptosis after ischemia-reperfusion in vitro involving translational suppression of the survival kinase PKB/Akt (Akt), and elucidated an alternative protective role of antioxidants in the regulation of Akt activity. Using human choriocarcinoma JEG-3 cells, we found that sustained activation of ER stress by tunicamycin or thapsigargin exacerbated apoptosis in oxygen-glucose-deprived cells during reoxygenation. This was mediated via a reduction in phosphorylated Akt secondary to down-regulation of protein translation rather than suppression of phosphorylation. Transient overexpression of wild-type Akt, but not kinase-dead Akt, in JEG-3 cells diminished tunicamycin-OGD reoxygenation-induced apoptosis. The antioxidants Trolox and Edaravone reduced apoptosis, but the protective effect of Trolox was abrogated by the PI3K inhibitor, LY294002. We speculate that sustained ER stress may contribute to the placental dysfunction seen in human pregnancy complications.
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PMID:Endoplasmic reticulum stress exacerbates ischemia-reperfusion-induced apoptosis through attenuation of Akt protein synthesis in human choriocarcinoma cells. 1716 73


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