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(Stroke. 2002;33:2687.)
© 2002 American Heart Association, Inc.

Original Contributions

Vascular NAD(P)H Oxidase Triggers Delayed Cerebral Vasospasm After Subarachnoid Hemorrhage in Rats

Dong Eun Kim, MS; Young Suk Suh, MD; Mi-Sook Lee, MS; Ki Young Kim, PhD; Jeong Hyun Lee, MS; Hyun Seung Lee, MS; Ki Whan Hong, MD, PhD Chi Dae Kim, MD, PhD

From the Department of Pharmacology, College of Medicine, Pusan National University, Busan, South Korea.

Correspondence and reprint requests to Chi Dae Kim, MD, PhD, Department of Pharmacology, College of Medicine, Pusan National University, 10 Ami-Dong 1 Ga, Seo-Gu, Busan 602-739, South Korea. E-mail chidkim{at}pusan.ac.kr

Background and Purpose– To clarify the role of vascular NAD(P)H oxidase in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH), both the activity and/or activation mechanisms of NAD(P)H oxidase in the cerebral vasculature and the effect of oxidase inhibition on SAH-induced cerebral vasospasm were assessed.

Methods— The changes in the luminal perimeter of the middle cerebral artery were measured histologically after SAH was induced according to a 2-hemorrhage model in rats. The NAD(P)H oxidase activity in the cerebral vasculature was measured with a lucigenin assay at different time intervals from 12 hours to 14 days after injection of autologous blood into cisterna magna. The membrane translocation of p47phox and the protein expression of membrane subunits (gp91phox and p22phox) of NAD(P)H oxidase were analyzed using Western blot analysis.

Results— The luminal perimeter of the middle cerebral artery started to decrease on day 1 and peaked on day 5 after a second injection of blood, and these changes were significantly ameliorated by treatment with an NAD(P)H oxidase inhibitor, diphenyleneiodonium. At 24 hours after the second injection of blood, both vascular production of superoxide anion and NAD(P)H oxidase activity were markedly increased with enhanced membrane translocation of p47phox, but by 48 hours the enzyme activity had regained normal values. However, no significant changes in the expression of gp91phox and p22phox were observed throughout the experiments.

Conclusions— These findings suggest that the activation of NAD(P)H oxidase through enhanced assembly of the oxidase components in the early stages of SAH might contribute to the delayed cerebral vasospasm in SAH rats.

Key Words: NADPH oxidase • reactive oxygen species • subarachnoid hemorrhage • vasospasm • rats

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