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

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.