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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 and the aftermath of reperfusion form a hypoxic/hyperoxic sequence of events that can trigger oxidative stress response cascades in neurons of the central nervous system. After transient ischemia there is an increase in intracellular Ca2+ release, extracellular glutamate, reactive oxygen species (ROS) and nitric oxide, genotoxic events that stimulate DNA repair. Increased oxidative stress and interrupted blood flow in ischemia, like DNA repair, also deplete cellular ATP and commit neurons to apoptosis. We report that levels of the DNA repair enzyme apurinic/apyrimidinic endonuclease (APE/Ref-1) decreased significantly in the hippocampus but not other brain areas after 6 h of reperfusion following an induced ischemic insult. This specific inhibition of APE/Ref-1 expression may affect the extent of apoptosis after ischemia.
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PMID:APE/Ref-1 responses to ischemia in rat brain. 992 39

We examined the effects of the free radical scavenger, 21-aminosteroid, on apurinic/apyrimidinic endonuclease (APE/Ref-1) protein expression and subsequent infarction volume after photothrombotic cortical cerebral ischemia in mice. Immunohistochemistry and Western blot analysis showed a significant reduction in APE/Ref-1 expression 6 and 24 h after ischemia in untreated animals, whereas in drug-treated animals the reduction was much less at the same time points. The administration of 21-aminosteroid significantly decreased subsequent infarction volume 3 days after ischemia. These data suggest that 21-aminosteroid prevents the early decrease of APE/Ref-1 expression, thereby reducing cortical infarction after photothrombotic cerebral ischemia.
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PMID:Neuroprotective effects of an antioxidant in cortical cerebral ischemia: prevention of early reduction of the apurinic/apyrimidinic endonuclease DNA repair enzyme. 1064 98

Early oxidative DNA damage is regarded to be an initiator of neuronal apoptotic cell death after cerebral ischemia. Although evidence suggests that HGF has the ability to protect cells from oxidative stress, it remains unclear as to how HGF suppresses oxidative DNA damage after cerebral ischemia. Apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1) is a multifunctional protein in the DNA base repair pathway that is responsible for repairing apurinic/apyrimidinic sites in DNA after oxidation. We demonstrated that both the immunoreactivity and the number of APE/Ref-1-positive cells in the hippocampal CA1 region were decreased after transient forebrain ischemia and that treatment with HGF suppressed this reduction. The expression of Cu/ZnSOD and MnSOD in the hippocampal CA1 region did not change after ischemia, regardless of treatment with or not with HGF. The activity of NADPH oxidase was increased mainly in glia-like cells in the hippocampal CA1 region after ischemia, and this increase was attenuated by HGF treatment. These results suggest that the protective effects of HGF against cerebral ischemia-induced cell death in the hippocampal CA1 region are related to the improvement of neuronal APE/Ref-1 expression and the inhibition of NADPH oxidase activity in glia-like cells.
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PMID:The protective effect of hepatocyte growth factor against cell death in the hippocampus after transient forebrain ischemia is related to the improvement of apurinic/apyrimidinic endonuclease/redox factor-1 level and inhibition of NADPH oxidase activity. 1697 82

Despite the correlation between changes in the levels of apurinic/apyrimidinic endonuclease and ischemic neuronal damage, no studies have addressed the question of whether increased APE/Ref-1 can prevent ischemic neuronal cell death in vivo. Using an adenoviral vector, we investigated whether increased APE/Ref-1 can inhibit the loss of APE/Ref-1 and thereby prevent oxidative DNA damage after transient focal cerebral ischemia. Mice were subjected to intraluminal suture occlusion of the middle cerebral artery for 1 h, followed by reperfusion. Pre-ischemic treatment of the adenoviral vector was introduced intracerebrally. An adenoviral vector harboring the entire APE/Ref-1 gene sequence or a control virus without the APE/Ref-1 sequence was introduced 3 days before ischemia/reperfusion (I/R). The reduction of APE/Ref-1 occurred before DNA fragmentation, which was shown by temporal and spatial analysis. Increased APE/Ref-1 significantly decreased DNA damage and infarct volume after I/R. In conclusion, increased APE/Ref-1 enhanced DNA repair and inhibited the induction of ischemic oxidative DNA damage and cerebral infarction after I/R.
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PMID:The adenoviral vector-mediated increase in apurinic/apyrimidinic endonuclease inhibits the induction of neuronal cell death after transient ischemic stroke in mice. 1937 86

Oxidative injury is involved in many diseases, including ischemic and neurodegenerative diseases. Antioxidant drugs can be used to relieve the oxidative injury caused by these diseases; however, there are very few antioxidant drugs available for clinical use. In this study, we found that 5-(hydroxymethyl)-2-furfural (5-HMF) protects against the oxidative damage induced by cerebral ischemia in rats or by hydrogen peroxide (H2O2) in PC12 cells. We demonstrated that 5-HMF performs this function via apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1). APE/Ref-1 is a multifunctional protein involved in oxidative DNA damage repair through the base excision repair (BER) pathway and in the regulation of the DNA-binding activity of several transcription factors. The current study focused on the role of APE/Ref-1 in the antioxidative properties of 5-HMF. The results show that 5-HMF inhibited the reduction of APE/Ref-1 protein level caused by cerebral ischemia-reperfusion injury in rats or H2O2 treatment in PC12 cells. Treatment with an APE/Ref-1 inhibitor blocked 5-HMF-induced protection, suggesting that APE/Ref-1's DNA repair function contributes to antioxidation. In conclusion, this study suggests that APE/Ref-1 may be a potential target for antioxidant drugs.
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PMID:5-HMF prevents against oxidative injury via APE/Ref-1. 2611 18

Recent studies have shown that tea polyphenols can cross the blood-brain barrier, inhibit apoptosis and play a neuroprotective role against cerebral ischemia. Furthermore, tea polyphenols can decrease DNA damage caused by free radicals. We hypothesized that tea polyphenols repair DNA damage and inhibit neuronal apoptosis during global cerebral ischemia/reperfusion. To test this hypothesis, we employed a rat model of global cerebral ischemia/reperfusion. We demonstrated that intraperitoneal injection of tea polyphenols immediately after reperfusion significantly reduced apoptosis in the hippocampal CA1 region; this effect started 6 hours following reperfusion. Immunohistochemical staining showed that tea polyphenols could reverse the ischemia/reperfusion-induced reduction in the expression of DNA repair proteins, X-ray repair cross-complementing protein 1 and apurinic/apyrimidinic endonuclease/redox factor-1 starting at 2 hours. Both effects lasted at least 72 hours. These experimental findings suggest that tea polyphenols promote DNA damage repair and protect against apoptosis in the brain.
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PMID:Tea polyphenols increase X-ray repair cross-complementing protein 1 and apurinic/apyrimidinic endonuclease/redox factor-1 expression in the hippocampus of rats during cerebral ischemia/reperfusion injury. 2553 60