Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early blood-brain barrier (BBB) disruption resulting from excessive neurovascular proteolysis by matrix metalloproteinases (MMPs) is closely associated with hemorrhagic transformation events in ischemic stroke. We have shown that normobaric hyperoxia (NBO) treatment reduces MMP-9 increase in the ischemic brain. The aim of this study was to determine whether NBO could attenuate MMP-9-mediated early BBB disruption following ischemic stroke. Rats were exposed to NBO (95% O(2)) or normoxia (30% O(2)) during 90-min middle cerebral artery occlusion, followed by 3-hour reperfusion. NBO-treated rats showed a significant reduction in Evan's blue extravasation in the ischemic hemisphere compared with normoxic rats. Topographically, Evan's blue leakage was mainly seen in the subcortical regions including the striatum, which was accompanied by increased gelatinolytic activity and reduced immunostaining for tight-junction protein, occludin. Increased gelatinolytic activities and occludin protein loss were also observed in isolated ischemic microvessels. Gel gelatin zymography identified that MMP-9 was the main enzymatic source in the cerebral microvessels. Incubation of brain slices or isolated microvessels with purified MMP-9 revealed specific degradation of occludin. Inhibition of MMP-9 by NBO or MMP-inhibitor, BB1101, significantly reduced occludin protein loss in ischemic microvessels. These results suggest that NBO attenuates early BBB disruption, and inhibition of MMP-9-mediated occludin degradation is an important mechanism for this protection.
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PMID:Normobaric hyperoxia attenuates early blood-brain barrier disruption by inhibiting MMP-9-mediated occludin degradation in focal cerebral ischemia. 1918 98

Normobaric hyperoxia (NBO) has been shown to be neuro- and vaso-protective during ischemic stroke. However, the underlying mechanisms remain to be fully elucidated. Activation of NADPH oxidase critically contributes to ischemic brain damage via increase in ROS production. We herein tested the hypothesis that NBO protects the blood-brain barrier (BBB) via inhibiting gp91phox (or called Nox2) containing NADPH oxidase in a mouse model of middle cerebral artery occlusion (MCAO). Wild-type C57/BL6 mice and gp91phoxknockout mice were given NBO (95% O2) or normoxia (21% O2) during 90-min MCAO, followed by 22.5 hrs of reperfusion. BBB damage was quantified by measuring Evans blue extravasation. The protein levels of matrix metalloproteinase-9 (MMP-9), tight junction protein occludin and gp91phox were assessed with western blot. Gel zymography was used to assess the gelatinolytic activity of MMP-9. In the wild type mice, cerebral ischemia and reperfusion led to remarkable Evans blue extravasation, significantly increased gp91phox and MMP-9 levels and decreased occludin levels in the ischemic brain tissue. In gp91phox knockout mice, the changes in Evans blue extravasation, MMP-9 and occludin were at much smaller magnitudes when compared to the wild type. Importantly, NBO treatment significantly reduced the changes in all measured parameters in wild type mice, while did not cause additional reductions in these changes when gp91phox was knocked out. These results indicate that activation of Nox2 containing NADPH oxidase is implicated in the induction of MMP-9, loss of occludin and BBB disruption in ischemic stroke, and inhibition of Nox2 may be an important mechanism underlying NBO-afforded BBB protection.
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PMID:Normobaric hyperoxia protects the blood brain barrier through inhibiting Nox2 containing NADPH oxidase in ischemic stroke. 2214 86