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

Ischemia induces immediate-early genes (IEGs) in brain. Since prolonged expression of some IEGs may precede neuronal death, some researchers have suggested that these IEGs mediate neuronal death. We therefore examined the effect of 5 and 10 min of global ischemia on the expression of the IEGs NGFI-A, NGFI-B, NGFI-C, egr-2, egr-3, and Nurr1 in gerbil brain. All of the IEGs were induced after 30 min of reperfusion in the hippocampus. Most of them were induced in several other regions as well, including cortex, hypothalamus, thalamus, and amygdala. The acute IEG induction decreased in most brain areas by 2-6 h. However, at 24 h following 5 min of ischemia NGFI-A continued to be expressed in the CA1 region and dentate gyrus. In the dentate gyrus, NGFI-C continued to be expressed for 24 h and egr-3 for as long as 72 h. In other brain areas, all of the IEGs returned to control levels by 72 h except in CA1, where most messenger RNA (mRNA) levels were decreased; this decrease correlated with marked neuronal loss. The persistent expression of NGFI-A in CA1 neurons destined to die and the persistent expression of NGFI-A, NGFI-C, and egr-3 genes in dentate granule cell neurons that survive may indicate that some transcription factors modulate cell death whereas others support cell survival when expressed for prolonged periods. The protein products of several transcription factors, including c-fos, are known to downregulate their own expression. The persistent expression of NGFI-A in the CA1 neurons destined to die could therefore be due to ischemia-induced transcriptional activation caused by, e.g., increased intracellular calcium levels plus a lack of negative feedback caused by the blockade of the translation of NGFI-A mRNA into protein.
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PMID:Global ischemia induces immediate-early genes encoding zinc finger transcription factors. 896 94

The prolonged expression of the leucine zipper fos/jun immediate early genes (IEG) has been correlated with neuronal death after cerebral ischemia. In this study, the expression of six zinc finger IEG was examined using in situ hybridization in adult rats after middle cerebral artery occlusion (MCAO) with the suture model. NGFI-A, NGFI-B, NGFI-C, egr-2, egr-3, and Nurr1 mRNA were all induced throughout the ipsilateral cortex at 1 hour to 12 hours after MCAO. The cortical induction for most of the genes was greatest in the anterior cingulate and the anterior cerebral artery (ACA) and middle cerebral artery (MCA) transition zone. All of the zinc finger IEG were induced at 1 hour in all regions of hippocampus. NGFI-A and NGFI-B were induced in ipsilateral thalamus. Within areas of infarction, the basal IEG mRNA expression, and expression of the housekeeping gene cyclophilin A mRNA, decreased below control levels by 12 hours after the ischemia. Immediate early gene expression outside areas of infarction returned to control levels in most brain regions by 24 hours except for egr-3, which continued to be induced in the MCA/ ACA transition zone for 24 hours, and NGFI-A, which continued to be expressed in specific regions of the thalamus for 72 hours. The induction of these IEG in the cortex is likely caused by ischemia-induced cortical spreading depression, with the hippocampal and thalamic IEG induction being caused by activation of efferent cortical pathways to these regions. The prominent induction of NGFI-B, NGFI-C, egr-2, and egr-3 in the anterior cingulate cortex, the ACA/MCA transition zone, and medial striatum could reflect the ischemic regions around MCA infarcts. The prolonged NGFI-A expression observed in thalamus in this study, and in CA1 of hippocampus after global ischemia in the gerbil in a previous study, suggests that the prolonged NGFI-A, expression could be the result of or the cause of the delayed cell death. Prolonged NGFI-A expression, like c-fos and c-jun, seems to provide a marker for slowly dying neurons.
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PMID:Expression of zinc finger immediate early genes in rat brain after permanent middle cerebral artery occlusion. 923 20

High density oligonucleotide arrays offer tremendous potential to study gene changes occurring in disease states. The authors described the first case of using a custom designed high density oligonucleotide probe array containing 750 genes to monitor the changes in mRNA transcript levels occurring after focal ischemia for a period of 3 hours. Permanent middle cerebral artery occlusion in the rat resulted in neuronal degeneration in the dorsolateral cortex and striatum over a time course of 24 hours. Comparing the changes in hybridization levels in the frontal and parietal cortices and the striatum, between the ipsilateral and contralateral sides of the brain using the probe arrays resulted in the up-regulation of 24 genes, which showed greater than a twofold change. Very few genes were found to be downregulated after the ischemic insult. Many of the immediate early genes (IEGs) such as c-fos, NGFI-A, NGFI-C, and Krox-20 were found to be robustly upregulated in the three different regions studied. Other genes that were up-regulated in perifocal regions included Arc, Inhibin-beta-A, and the phosphatases MKP-1 and MKP-3. The hybridization signal intensity from the probe arrays enabled quantification of many genes relative to one another, and robust changes in expression were obtained with very little interanimal variability. Furthermore, the authors were able to validate the increased expression of NGFI-C and Arc using in situ hybridization. This represented the first example of using high density oligonucleotide probe arrays in studying the expression of many genes in parallel and in discrete brain regions after focal ischemia.
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PMID:Parallel gene expression monitoring using oligonucleotide probe arrays of multiple transcripts with an animal model of focal ischemia. 1090 38