Oxidative stress after subarachnoid hemorrhage in gp91phox knockout mice.
BACKGROUND
Oxidative stress largely contributes to early brain injury after subarachnoid hemorrhage (SAH). One of the major sources of reactive oxygen species is NADPH oxidase, upregulated after SAH. We hypothesized that NADPH oxidase-induced oxidative stress plays a major causative role in early brain injury after SAH.


METHODS
Using gp91phox knockout (ko) and wild-type (wt) mice, we studied early brain injury in the endovascular perforation model of SAH. Mortality rate, cerebral edema, oxidative stress, and superoxide production were measured at 24 h after SAH. Neurological evaluation was done at 23 h after SAH surgery.


RESULTS
Genotyping confirmed the existence of a nonfunctional gp91phox gene in the ko mice. CBF measurements did not show differences in SAH-induced acute ischemia between ko and wt mice. SAH caused a significant increase of water content in the ipsilateral hemisphere as well as an increase of Malondialdehyde (MDA) levels and superoxide production. There were no significant differences in post-SAH mortality rate, brain water content and the intensity of the oxidative stress between knockout and wild type groups of mice.


CONCLUSIONS
Our results suggest that gp91phox is not critically important to the early brain injury after SAH. An adaptive compensatory mechanism for free radical production in knockout mice is discussed.
Liu
Shimin
S
Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.
Tang
Jiping
J
Ostrowski
Robert P
RP
Titova
Elena
E
Monroe
Cara
C
Chen
Wanqiu
W
Lo
Wendy
W
Martin
Robert
R
Zhang
John H
JH
D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology / Q000503:physiopathology; D001925:Brain Damage, Chronic / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D001929:Brain Edema / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D002536:Cerebral Arteries / Q000201:enzymology / Q000503:physiopathology; D005609:Free Radicals / Q000378:metabolism; D005819:Genetic Markers / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D009410:Nerve Degeneration / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D018384:Oxidative Stress / Q000235:genetics*; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000201:enzymology / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism