Inhibition of NADPH oxidase attenuates vasospasm after experimental subarachnoid hemorrhage in rats

• Published in: Stroke (1970) Vol. 36; no. 5; pp. 1059 - 1064
• Main Authors: Zheng, Jie-Sheng, Zhan, Ren-Ya, Zheng, Shu-Sen, Zhou, Yong-Qing, Tong, Ying, Wan, Shu
• Format: Journal Article
• Language: English
• Published: United States 01.05.2005
• Subjects: Acetophenones - therapeutic use; Animals; Basilar Artery - drug effects; Basilar Artery - pathology; Enzyme Inhibitors - therapeutic use; Male; NADPH Oxidases - antagonists & inhibitors; Phosphoproteins - metabolism; Protein Transport - drug effects; Rats; Rats, Sprague-Dawley; Subarachnoid Hemorrhage - complications; Superoxides - metabolism; Vasospasm, Intracranial - drug therapy; Vasospasm, Intracranial - etiology; Vasospasm, Intracranial - metabolism
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.str.0000163102.49888.b7

The purpose of this study is to investigate whether apocynin, an NADPH oxidase inhibitor, attenuates vasospasm after experimental subarachnoid hemorrhage (SAH) in rats. Rats were subjected to endovascular perforation of the right anterior cerebral artery or sham surgery. Beginning 2 hours after SAH, rats were administered 50 mg/kg apocynin or vehicle by intraperitoneal injection 3 times daily for 2 days. In SAH rats, apocynin treatment enlarged basilar artery diameter (SAH/apocynin=253+/-71 microm, SAH/saline=191+/-60 microm, P<0.01; SAH=190+/-58 microm, sham=276+/-52 microm, P<0.01), reduced neurological deficits (SAH/apocynin=24+/-6.5, SAH/saline=18+/-5.3, P<0.05; SAH=18+/-4.7, sham=27+/-0, P<0.01), decreased NADPH oxidase activity (SAH/apocynin=18.4+/-3.7, SAH/saline=25.7+/-5.2, P<0.05; SAH=27.5+/-5.8, sham=15.4+/-4.5 nmol/min per mg protein, P<0.05), decreased superoxide level (SAH/apocynin=6.5+/-1.8, SAH/saline=9.6+/-2.2, P<0.05; SAH=9.8+/-1.9, sham=4.9+/-0.9 arbitrary units, P<0.05), and lowered membrane translocation of NADPH oxidase subunit p47phox. Inhibition of NADPH oxidase attenuates delayed cerebral vasospasm after experimental SAH, suggesting that the inhibition of NADPH oxidase may provide a therapeutic strategy for vasospasm after SAH.