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- Title
Normobaric hyperoxia inhibits NADPH oxidase-mediated matrix metalloproteinase-9 induction in cerebral microvessels in experimental stroke.
- Authors
Wenlan Liu; Sood, Rohit; Qingchuan Chen; Sakoglu, Unal; Hendren, Jill; Çetin, Özdemir; Miyake, Minoru; Ke Jian Liu
- Abstract
Matrix metalloproteinase-9 (MMP-9) and NADPH oxidase contribute to blood–brain barrier (BBB) disruption after ischemic stroke. We have previously shown that normobaric hyperoxia (NBO) treatment reduces MMP-9 and oxygen free radical generation in ischemic brain. In this study, we tested the hypothesis that NBO protects the BBB through inhibiting NADPH oxidase-mediated MMP-9 induction in transient focal cerebral ischemia. Male Sprague–Dawley rats ( n = 69) were given NBO (95% O2) or normoxia (21% O2) during 90-min filament occlusion of the middle cerebral artery. Cerebral microvessels were isolated for analyzing MMP-9 and NADPH oxidase. BBB damage was non-invasively quantified with magnetic resonance imaging. In normoxic rats, both NADPH oxidase catalytic subunit gp91phox and MMP-9 expression were up-regulated in ischemic hemispheric microvessels after 90-min middle cerebral artery occlusion with 22.5 h reperfusion. Inhibition of NADPH oxidase with apocynin reduced the MMP-9 increase, indicating a causal link between NADPH oxidase-derived superoxide and MMP-9 induction. NBO treatment inhibited gp91phox expression, NADPH oxidase activity, and MMP-9 induction, which led to significantly less BBB damage and brain edema in the ischemic brain. These results suggest that gp91phox containing NADPH oxidase plays an important role in MMP-9 induction in ischemic BBB microvasculature, and that NBO treatment may attenuate MMP-9 induction and brain edema through inhibiting NADPH oxidase after transient cerebral ischemia.
- Subjects
METALLOPROTEINASES; CEREBROVASCULAR disease; HYPOXEMIA; BLOOD-brain barrier; OXIDASES; CEREBRAL ischemia
- Publication
Journal of Neurochemistry, 2008, Vol 107, Issue 5, p1196
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2008.05664.x