Normobaric hyperoxia inhibits NADPH oxidase-mediated matrix metalloproteinase-9 induction in cerebral microvessels in experimental stroke

被引：95

作者：

Liu, Wenlan ^{[1
]}

Sood, Rohit ^{[2
]}

Chen, Qingchuan ^{[1
]}

Sakoglu, Unal ^{[2
]}

Hendren, Jill ^{[1
]}

Cetin, Oezdemir ^{[2
]}

Miyake, Minoru ^{[1
,3
]}

Liu, Ke Jian ^{[1
,2
]}

机构：

[1] Univ New Mexico, Coll Pharm, Hlth Sci Ctr, Albuquerque, NM 87131 USA

[2] Univ New Mexico, Dept Neurol, Hlth Sci Ctr, Albuquerque, NM 87131 USA

[3] Kagawa Univ, Sch Med, Dept Oral & Maxillofacial Surg, Kagawa, Japan

来源：

JOURNAL OF NEUROCHEMISTRY | 2008年 / 107卷 / 05期

基金：

美国国家卫生研究院;

关键词：

Blood-brain barrier; matrix metalloproteinase; NADPH oxidase; oxygen; stroke;

D O I：

10.1111/j.1471-4159.2008.05664.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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% O-2) or normoxia (21% O-2) 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 gp91(phox) 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 gp91(phox) 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 gp91(phox) 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.

引用

页码：1196 / 1205

页数：10

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