Inhibition of NADPH oxidase attenuates vasospasm after experimental subarachnoid hemorrhage in rats.
OBJECTIVE
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.
Zheng
Jie-Sheng
JS
Department of Neurosurgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. zhengjiesheng@126.com
Zhan
Ren-Ya
RY
Zheng
Shu-Sen
SS
Zhou
Yong-Qing
YQ
Tong
Ying
Y
Wan
Shu
S
D000098:Acetophenones / Q000627:therapeutic use*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000473:pathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013481:Superoxides / Q000378:metabolism; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism
D000098:Acetophenones; D004791:Enzyme Inhibitors; D010750:Phosphoproteins; D013481:Superoxides; C056165:acetovanillone; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1