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

ABSTRACT

BACKGROUND AND PURPOSE: The purpose of this study is to investigate whether apocynin, an NADPH oxidase inhibitor, attenuates vasospasm after experimental subarachnoid hemorrhage (SAH) in rats. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.