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

Loss of intracellular calcium homeostasis has been regarded an important factor underlying neuron cell death after cerebral ischemic insult. In the brain, a major mechanism for regulation of intracellular calcium is through the signal transduction pathway involving hydrolysis of poly-phosphoinositides and release of the second messenger, inositol 1,4,5-trisphosphate (IP3). IP3 mobilizes calcium by interacting with an intracellular receptor. Upon its release after agonist stimulation, this second messenger is catabolized by a 3-kinase and a 5-phosphatase. In this study, in situ hybridization was carried out to examine the mRNA expression of IP3, receptor (IP3R) and IP3 3-kinase (IP3K) in rat brain cortex after transient focal cerebral ischemia induced by temporary occlusion of the middle cerebral artery (MCA) and the common carotid arteries (CCAs). Results indicate a large decrease (52%) in IP3R mRNA levels in the ischemic cortex as compared to that in the contralateral side at 4 h after a 45 min ischemic insult. By 16 h, practically no IP3R mRNA could be detected in the ischemic cortex. On the other hand, IP3K mRNA levels remained unaltered until 16 h after reperfusion, during which time, expression in the infarct core decreased but that surrounding the core area increased instead. Hybridization of adjacent brain sections with probes for neuron specific enolase (NSE) and beta-actin indicated also a time-dependent decrease in mRNA levels after ischemia, but these changes were less dramatic as compared to IP3R. At 16 and 24 h after reperfusion, there was an increase in beta-actin mRNA in cortical areas outside the MCA cortex, suggesting of reactive gliosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In situ hybridization of mRNA expression for IP3 receptor and IP3-3-kinase in rat brain after transient focal cerebral ischemia. 750 Aug 36

The receptor-mediated poly-phosphoinositide (PI) signalling pathway is known to play an important role in maintaining intracellular calcium homeostasis, which in turn, is critical for mediating neuronal function. In this study, we examined the effects of focal cerebral ischemia induced in rats by temporary occlusion of the middle cerebral artery (MCA) and both common carotid arteries (CCAs) on this signal transduction pathway. Results indicate that several parts of the pathway are altered, both during the early phase of focal cerebral ischemic insult and after recirculation. Cerebral ischemia induced a decrease in levels of phosphatidylinositol 4,5-bisphosphate (PIP2) in the ischemic MCA cortex, due partly to stimulated poly-PI hydrolysis and partly to the depletion of ATP required for resynthesis of this substrate. ATP depletion during ischemia was also attributed to a sustained decrease in inositol 1,4,5-trisphosphate (IP3) levels. On the other hand, the decline in IP3 3-kinase activity after 30 min of ischemic insult was not related to ATP depletion. During reperfusion upon prolonged ischemic insult, neither IP3 level nor IP3 3-kinase activity were able to show recovery after reperfusion, despite that ATP levels recovered by 80%. In situ hybridization studies indicated a decrease in mRNA expression of IP3 receptor but not IP3 3-kinase during the initial 4 h of reperfusion after a 45 min ischemic insult. Under this same condition, insulted cortical neurons started to show morphological changes between 4 and 8 h after reperfusion and extensive cell death could be observed by 16 h. Taken together, these results demonstrated early and delayed changes in the poly-PI signalling pathway due to focal cerebral ischemia. These effects are likely to cause impairment in neuronal function and underline the process of cerebral ischemic damage.
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PMID:Poly-phosphoinositide-mediated messengers in focal cerebral ischemia and reperfusion. 890 56