Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the postischemic alterations in [3H]MK-801, [3H]muscimol, and [3H]naloxone binding in the gerbil brain, and examined the effect of pentobarbital against these alterations. [3H]MK-801, [3H]muscimol, and [3H]naloxone were used to label N-methyl-D-aspartate (NMDA), gamma-aminobutyric acidA (GABAA), and opiate receptors, respectively. Transient cerebral ischemia was induced for 10 min, and pentobarbital (40 mg/kg) was administered intraperitoneally 30 min before ischemia. Five hours after ischemia, no conspicuous alteration in [3H]MK-801, [3H]muscimol, and [3H]naloxone binding was found in the striatum and hippocampus. Seven days after ischemia, [3H]MK-801 and [3H]naloxone binding was significantly decreased in the striatum and hippocampal area where histological neuronal damage was noted. By contrast, no significant change in [3H]muscimol binding was seen in the above regions except for the hippocampal CA3 sector. The treatment of pentobarbital caused a significant alteration in the binding of [3H]naloxone and [3H]muscimol in various brain areas 5 h after ischemia. However, this drug showed no significant change in [3H]MK-801 binding in the brain. Seven days after ischemia, pentobarbital partly ameliorated a significant reduction in [3H]MK-801 and [3H]naloxone binding in the striatum and hippocampus. A histological study also showed that pentobarbital afforded neuronal protection against the damage to the brain except for the hippocampal CA1 sector 7 days after ischemia. These results suggest that NMDA and opiate receptors are damaged after ischemia, whereas GABAA receptors are unaffected. They also demonstrate that opiate receptors are severe affected by the treatment of pentobarbital, compared with NMDA and GABAA receptors. These findings are of interest in relation to the mechanism of ischemic neuronal damage.
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PMID:Effect of pentobarbital on postischemic MK-801, muscimol, and naloxone bindings in the gerbil brain. 782 Jun 43

We examined the alterations of opioid (naloxone), N-methyl-D-aspartate and gamma-aminobutyric acidA receptors in the gerbil brain 7 days after cerebral ischemia using [3H]naloxone, [3H]MK-801 and [3H]muscimol autoradiography, respectively. We also evaluated the effect of vinconate against the alterations in these receptors. Transient cerebral ischemia was induced for 10 minutes, and vinconate (100 and 300 mg/kg) was given intraperitoneally 10 minutes before ischemia. [3H]MK-801 binding showed a more severe reduction than [3H]naloxone binding 7 days after cerebral ischemia, whereas [3H]muscimol binding was unchanged in almost all brain regions. Vinconate showed a significant prevention against the reduction in [3H]naloxone binding in all brain areas. This drug also prevented a significant reduction in [3H]MK-801 binding in most of the brain regions. Furthermore, [3H]muscimol binding in vinconate-treated gerbils exhibited a significant increase compared with that in sham-operated animals. These results show that opioid and N-methyl-D-aspartate receptors are very sensitive to transient cerebral ischemia, whereas gamma-aminobutyric acidA receptors are particularly resistant. They also suggest that vinconate has a potent protective effect against the alterations of opioid and N-methyl-D-aspartate receptors. These findings might be of interest in relation to the mechanism of ischemic neuronal damage.
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PMID:Effect of vinconate against alterations in [3H]naloxone, [3H]MK-801 and [3H]muscimol bindings after transient cerebral ischemia in gerbils. 811 27

Transient cerebral ischemia causes long-lasting inhibition of protein synthesis despite recovery of energy metabolism. We investigated the question if this inhibition is due to the formation of a suppression factor which interferes with the function of the protein synthesizing machinery. For this purpose rats were submitted to 20 minutes four vessel-occlusion followed by recirculation times from 30 minutes to 7 days. Post-mitochondrial supernatant (PMS) from various brain regions was added to a self-contained, cell-free rabbit reticulocyte translational system, and the effect on in vitro protein synthesis was assessed by measuring 14C-leucine incorporation over a duration of 45 minutes. PMS prepared at the end of ischemia from hippocampus, striatum and cerebellum inhibited in vitro protein synthesis by 40%-60% but there was only a minor inhibition by PMS from cerebral cortex. During post-ischemic recirculation cortical PMS transiently induced inhibition of in vitro protein synthesis by 30% but this effect gradually disappeared within one week. The inhibition caused by PMS from hippocampus, striatum and cerebellum was not reversed during recirculation and still amounted to about 40% after 7 days. Inhibition of in vitro protein synthesis could be blocked by heating PMS to 100 degrees C, indicating that the suppressor factor is a protein. The comparison of the in vitro effect of postischemic PMS with previously described in vivo inhibition of protein synthesis demonstrates that the here observed suppressor factor is not able to explain the overall disturbance of protein synthesis in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of global ischemia and recirculation of rat brain on protein synthesis in vitro. 819 40

We investigated the postischemic alterations in dopamine D1 receptor and Ca2+/calmodulin independent cyclic adenosine monophosphate (cyclic AMP) selective phosphodiesterase in gerbils and examined the effect of pentobarbital on these alterations. [3H]SCH 23390 and [3H]rolipram, respectively, were used to label dopamine D1 receptor and Ca2+/calmodulin independent cyclic-AMP selective phosphodiesterase. Transient cerebral ischemia was induced for 10 min, and pentobarbital (40 mg/kg) was administered intraperitoneally 30 min prior to ischemia. 5 h after ischemia, [3H]rolipram binding decreased significantly in the striatum and hippocampus, whereas no significant change was found in [3H]SCH 23390 binding. 7 days after ischemia, however, there was a marked reduction in both [3H]SCH 23390 and [3H]rolipram binding in the striatum and hippocampus, where histological neuronal damage was found. Pentobarbital significantly ameliorated postischemic decreases in [3H]rolipram binding both 5 h and 7 days after recirculation in most areas studied. Furthermore, this drug significantly prevented postischemic reduction in [3H]SCH 23390 binding (only) 7 days after ischemia. These results suggest that alteration of cyclic AMP selective phosphodiesterase is more sensitive at an earlier stage after ischemic insult than that of dopamine D1 receptors. Our results also demonstrate that pentobarbital reduces the alteration in [3H]SCH 23390 and [3H]rolipram binding after cerebral ischemia.
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PMID:Effect of pentobarbital on postischemic SCH 23390 and rolipram binding in gerbil brain. 822 65

Inductions of mRNAs for heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 were examined in the cerebral cortex, cerebellum, heart, lung, kidney, and liver of gerbils after a 10-min transient forebrain ischemia. HSP70 mRNA was normally expressed in a small amount in the cerebellum, lung, and kidney, but was not expressed in the heart or liver in a detectable amount. A very small amount of HSP70 mRNA was also present in the cerebral cortex. HSC70 mRNA was normally present in all the organs examined with a variety in the amount. Eight hours after the cerebral ischemia, the level of HSP70 mRNA increased in the cerebral cortex, lung, and kidney. HSC70 mRNA levels also increased in all the organs. However, the increase of HSC70 mRNA was remarkable in the heart. Transient cerebral ischemia caused subsequent hyperthermia. Treatment of gerbils with an artificial hyperthermia without cerebral ischemia increased the HSP70 and HSC70 mRNA levels as well. However, the HSC70 mRNA level in the heart after cerebral ischemia was much higher than that in the case with hyperthermic treatment. These results suggest that HSC70 mRNA was preferentially induced in the heart after transient forebrain ischemia that was not only due to the subsequent hyperthermia.
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PMID:Preferential expression of HSC70 heat shock mRNA in gerbil heart after transient brain ischemia. 826 47

Transient cerebral ischemia can produce irreversible neuronal damage and permanent learning and memory impairments in humans. This study examined whether ischemia-induced brain damage in rats results in impairments on the delayed nonmatching-to-sample (DNMS) task, a nonspatial recognition task analogous to tests on which amnesic patients display impairments. Male Wistar rats received either sham surgery or 20-min forebrain ischemia induced by bilateral carotid occlusion and hypotension. Four weeks after surgery, ischemic rats were significantly impaired in both learning and performing the DNMS task at retention intervals up to 5 min. Extensive presurgical training did not reduce this impairment. Observable cell loss in ischemic rats was limited to CA1 pyramidal neurons and a subset of cells in the dentate gyrus. The results indicate that ischemic damage to the hippocampus in rats results in recognition memory deficits similar to those produced by ischemic damage in humans.
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PMID:Impaired object recognition memory in rats following ischemia-induced damage to the hippocampus. 844 57

Transient cerebral ischemia induces, besides delayed neurodegeneration in selected brain structures, a number of early responses which may mediate ischemic injury/repair processes. Here we report that 5 min exposure to cerebral ischemia in gerbils induces a rapid inhibition and subsequent translocation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). These changes were partially reversible during a 24 h post-ischemic recovery. Concomitantly the total amount of the enzyme protein, as revealed by Western blotting (alpha-subunit specific), remained stable. This is consistent with our previous hypothesis, that the mechanism of ischemic CaMKII down-regulation involves a reversible posttranslational modification-(auto)phosphorylation, rather than the degradation of enzyme protein. The effectiveness of known modulators of post-ischemic outcome in counteracting CaMKII inhibition was tested. Three of these drugs, namely dizocilpine (MK-801), N-nitro-L-arginine methyl ester (L-NAME) and ginkgolide (BN52021), all significantly attenuated the enzyme response to ischemia, whereas an obvious diversity in the time-course of their actions implicates different mechanisms involved.
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PMID:Changes of Ca2+/calmodulin-dependent protein kinase-II after transient ischemia in gerbil hippocampus. 878 2

Transient cerebral ischemia was produced in rats using the four-vessel occlusion model. After 30 min ischemia and 2, 4, 8, or 24 h of recirculation, total RNA was isolated from the cortex, striatum and hippocampus and reverse transcribed into cDNA. Endoplasmic reticulum (ER) calcium-ATPase (SERCA, subunit 2b) cDNA was amplified using appropriate primers. Ischemia-induced changes in SERCA mRNA levels were analyzed by quantitative polymerase chain reaction (PCR). For quantification, each PCR reaction was run in the presence of an internal standard. In control brains SERCA mRNA levels amounted to 392 +/- 43,431 +/- 86, and 409 +/- 21 micrograms mRNA/g total RNA in the cortex, striatum and hippocampus, respectively. SERCA mRNA levels did not change significantly during the first 8 h of recovery. After 24 h of recovery, however, SERCA mRNA levels decreased sharply in the hippocampus and striatum (P < 0.001 versus control) but not in the cortex. It is concluded that in vulnerable brain structures a post-ischemic disturbance in ER calcium homeostasis may limit the recovery of neurons from metabolic stress.
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PMID:Changes in endoplasmic reticulum Ca(2-)-ATPase mRNA levels in transient cerebral ischemia of rat: a quantitative polymerase chain reaction study. 890 35

The mechanisms of ischemic cell damage are still not fully understood. It has been shown that alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA)/kainate receptor antagonists, such as 6-nitro-7- sulphamoyl-benzo-(f)-quinoxaline-2, 3-dione (NBQX), are neuroprotective in models of transient forebrain ischemia, even when applied during recovery, indicating that nonNMDA receptors may play a pivotal role in ischemic cell damage. In the present series of experiments, we studied whether transient cerebral ischemia causes changes in the extent of mRNA editing of AMPA/kainate receptor subunits, a reaction critical for the control of calcium flux through nonNMDA receptor ion channels. Transient cerebral ischemia was produced in rats using the four-vessel occlusion (4-VO) model. After 30 min of ischemia, brains were recirculated for 4, 8, or 24 h. Total RNA was extracted from the cortex, striatum, and hippocampus in order to analyze the extent of mRNA editing of the glutamate receptor subunits GluR2, GluR5, and GluR6. RNA was converted by reverse transcription into cDNA, which was used as a template for subunit-specific polymerase chain reaction (PCR) to amplify a product across the edited base A (A edited to I in the second transmembrane-spanning regions of GluR2, GluR5, and GluR6). PCR products were analyzed with the restriction enzyme Bbv 1, which recognizes the cDNA sequence GCAGC originating from unedited but not that originating from edited GluR2, GluR5, or GluR6 mRNA (GCGGC, the base I is read as G). Restriction digests were electrophoresed, and the bands visualized with ethidium bromide and then photographed. The extent of mRNA editing of the different subunits was quantified using image analysis and appropriate standards. In all control brains studied, GluR2 mRNA was completely edited and remained so after reversible cerebral ischemia. The extent of GluR5 mRNA editing was significantly upregulated in the striatum (from 39 +/- 6% in controls to 57 +/- 9 and 56 +/- 7 after 4 and 8 h of recovery, respectively, p < 0.05 versus control) but not in the cortex and hippocampus. The extent of GluR6 mRNA editing was significantly reduced after 24 h of recovery: in the cortex, from 92 +/- 1 to 78 +/- 6% (p < 0.01); in the striatum, from 91 +/- 2 to 79 +/- 1% (p < 0.001); and in the hippocampus, from 90 +/- 3 to 80 +/- 2% (p < 0.05). A significant reduction was already apparent in the striatum after 4 h of recovery (p < 0.05). Results indicate that mRNA editing is regulated differently in each of the glutamate receptor subunits GluR2, GluR5, and GluR6 after transient cerebral ischemia. The ischemia-induced upregulation of GluR5 mRNA editing observed in the striatum may be indicative of a higher sensitivity to transient ischemia of neurons that exhibit a large fraction of unedited GluR5 mRNA. This assumption is corroborated by the observation (Mackler and Eberwine, 1993) that GluR5 mRNA is completely unedited in neurons of the hippocampal CA1-subfield, a region most vulnerable to transient cerebral ischemia. Whether the decrease in GluR6 mRNA editing observed in all brain structures after ischemia results from a disturbance of the editing reaction or from glial proliferation will have to be established in further experiments. Studying ischemia-induced changes in mRNA editing of glutamate receptor subunits GluR5 and GluR6 may help to elucidate the molecular mechanisms of ischemic cell damage.
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PMID:RNA editing of glutamate receptor subunits GluR2, GluR5 and GluR6 in transient cerebral ischemia in the rat. 896 93

Despite years of research, delayed cerebral vasospasm remains a serious complication of subarachnoid hemorrhage (SAH). Recently, it has been proposed that endothelin-1 (ET-1) mediates vasospasm. The authors examined this hypothesis in a series of experiments. In a primate model of SAH, serial ET-1 levels were measured in samples from the perivascular space by using a microdialysis technique and in cerebrospinal fluid (CSF) and plasma during the development and resolution of delayed vasospasm. To determine whether elevated ET-1 production was a direct cause of vasospasm or acted secondary to ischemia, the authors also measured ET-1 levels in plasma and CSF after transient cerebral ischemia. To elucidate the source of ET-1, they measured its production in cultures of endothelial cells and astrocytes exposed to oxyhemoglobin (10 microM), methemoglobin (10 microM), or hypoxia (11% oxygen). There was no correlation between the perivascular levels of ET-1 and the development of vasospasm or its resolution. Cerebrospinal fluid and plasma levels of ET-1 were not affected by vasospasm (CSF ET-1 levels were 9.3 +/- 2.2 pg/ml and ET-1 plasma levels were 1.2 +/- 0.6 pg/ml) before SAH and remained unchanged when vasospasm developed (7.1 +/- 1.7 pg/ml in CSF and 2.7 +/- 1.5 pg/ml in plasma). Transient cerebral ischemia evoked an increase of ET-1 levels in CSF (1 +/- 0.4 pg/ml at the occlusion vs. 3.1 +/- 0.6 pg/ml 4 hours after reperfusion; p < 0.05), which returned to normal (0.7 +/- 0.3 pg/ml) after 24 hours. Endothelial cells and astrocytes in culture showed inhibition of ET-1 production 6 hours after exposure to hemoglobins. Hypoxia inhibited ET-1 release by endothelial cells at 24 hours (6.4 +/- 0.8 pg/ml vs. 0.1 +/- 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05) and at 48 hours (6.4 +/- 0.6 pg/ml vs. 0 +/- 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05), but in astrocytes hypoxia induced an increase of ET-1 at 6 hours (1.5 +/- 0.6 vs. 6.4 +/- 1.1 pg/ml, control vs. hypoxic astrocytes; p < 0.05). Endothelin-1 is released from astrocytes, but not endothelial cells, during hypoxia and is released from the brain after transient ischemia. There is no relationship between ET-1 and vasospasm in vivo or between ET-1 and oxyhemoglobin, a putative agent of vasospasm, in vitro. The increase in ET-1 levels in CSF after SAH from a ruptured intracranial aneurysm appears to be the result of cerebral ischemia rather than reflecting the cause of cerebral vasospasm.
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PMID:Source and cause of endothelin-1 release into cerebrospinal fluid after subarachnoid hemorrhage. 925 95


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