Gene/Protein Disease Symptom Drug Enzyme Compound
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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 is a major cause of adult disability and death worldwide. Evidence suggests that Bax-dependent initiation and activation of intrinsic apoptotic pathways contribute to ischemic brain injury. We investigated the Bax-inhibiting peptide VPALR, designed from the rat Ku70-Bax inhibiting domain, on the apoptotic neuronal cell death and behavioral deficits following global cerebral ischemia. The pentapeptide was infused into the left lateral ventricle of the rat brain by intracerebroventricular (i.c.v.) injection 1 h after cerebral ischemia, and results showed that it highly permeated hippocampal neurons and bound to Bax protein in vivo. Post-treatment with VPALR reduced the delayed neuronal damage by approximately 78% compared to the non-treated ischemic control and scrambled peptide-treated rats. TUNEL analysis revealed that VPALR markedly reduced the ischemia-induced increase in apoptotic neuronal death in rat hippocampal CA1 region. VPALR post-treatment also significantly attenuated Bax activation and its mitochondrial translocation as compared with scrambled peptide-treated animals. Concomitantly, Bax-inhibiting peptide-treated rats showed reduced cytochrome c release from mitochondria to cytosol and reduced caspase-3 activation in response to cerebral ischemia, indicating that activation of the intrinsic apoptotic pathway was reduced. Furthermore, Bax-inhibiting peptide improved spatial learning and memory performance in the Morris water maze, which was seriously affected by global cerebral ischemia. In conclusion, Bax inhibition by cell-permeable pentapeptides reduced apoptotic neuronal injury in the hippocampal CA1 region and behavioral deficits following global ischemia. These results suggest that Bax is a potential target for pharmacological neuroprotection and that Bax-inhibiting peptide may be a promising neuroprotective strategy for cerebral ischemia.
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PMID:Post-treatment of Bax-inhibiting peptide reduces neuronal death and behavioral deficits following global cerebral ischemia. 2116 43

MicroRNAs are small, non-coding RNA molecules that regulate gene expression, and miR-124 is the most abundant miRNA in the brain. Studies have shown that miR-124 is clearly reduced in the ischemic brain after stroke; however, the role of miR-124 after stroke is less well studied. Using TargetScan, MicroCosm Targets version 5, and microRNA.org databases, we identified miR-124 as a possible regulator of the DNA repair protein Ku70. We validated that Ku70 is a target for miR-124 with a luciferase reporter activity assay. Moreover, adult rats subjected to focal cerebral ischemia exhibited a substantial reduction of miR-124 expression, which was inversely upregulated by Ku70 expression. In vivo treatment with miR-124 antagomir effectively enhanced Ku70 mRNA and protein levels in the ischemic region. Furthermore, knockdown of cerebral miR-124 reduced cell death and infarct size and improved neurological outcomes. Our data demonstrate that miR-124 is an endogenous regulator of Ku70 that improves ischemia/reperfusion (I/R)-induced brain injury and dysfunction.
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PMID:MicroRNA-124 (miR-124) regulates Ku70 expression and is correlated with neuronal death induced by ischemia/reperfusion. 2416 54

Previous studies have indicated that electrical stimulation of the cerebellar fastigial nucleus in rats may reduce brain infarct size, increase the expression of Ku70 in cerebral ischemia/reperfusion area, and decrease the number of apoptotic neurons. However, the anti-apoptotic mechanism of Ku70 remains unclear. In this study, fastigial nucleus stimulation was given to rats 24, 48, and 72 hours before cerebral ischemia/reperfusion injury. Results from the electrical stimulation group revealed that rats exhibited a reduction in brain infarct size, a significant increase in the expression of Ku70 in cerebral ischemia/reperfusion regions, and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Double immunofluorescence staining revealed no co-localization of Ku70 with TUNEL-positive cells. However, Ku70 partly co-localized with Bax protein in the cytoplasm of rats with cerebral ischemia/reperfusion injury. These findings suggest an involvement of Ku70 with Bax in the cytoplasm of rats exposed to electrical stimulation of the cerebellar fastigial nucleus, and may thus provide an understanding into the anti-apoptotic activity of Ku70 in cerebral ischemia/reperfusion injury.
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PMID:Neuronal apoptosis in cerebral ischemia/reperfusion area following electrical stimulation of fastigial nucleus. 2520 80

Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor (U0126) was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and Ku70 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These findings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and accelerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/reperfusion.
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PMID:Regulation of extracellular signal-regulated kinase 1/2 influences hippocampal neuronal survival in a rat model of diabetic cerebral ischemia. 2520 83