Hyperbaric oxygen suppresses NADPH oxidase in a rat subarachnoid hemorrhage model.
OBJECTIVE
One of the major contributors to brain injury after subarachnoid hemorrhage (SAH) is oxidative stress, and 1 of the major enzymatic sources of superoxide anion production in the brain is NADPH oxidase. Therefore, we studied whether hyperbaric oxygen (HBO) suppresses neuronal NADPH oxidase in a rat model of SAH.


METHODS
Eighty-three Sprague-Dawley male rats were assigned to sham, SAH, and SAH treated with HBO groups. SAH was induced by endovascular perforation. HBO (2.8 atmospheres absolutes for 2 hours) was started at 1 hour after perforation. Rats were euthanized at 6 or 24 hours, and brains were collected for histology, biochemistry, and molecular biology studies including NADPH oxidase activity, gp91phox mRNA expression, and lipid peroxidation assays. Mortality and neurological scores were evaluated.


RESULTS
We observed an increased neuronal immunoreactivity of gp91phox at 24 hours after SAH. The upregulation of gp91phox mRNA was associated with increased oxidative stress. HBO decreased NADPH oxidase expression, activity, and the level of oxidative stress at 24 hours after SAH. HBO reduced neuronal injury and improved functional performance throughout the observation period.


CONCLUSIONS
HBO suppresses NADPH oxidase and oxidative stress in cerebral tissues at 24 hours after SAH.
Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92354, USA.
Robert P
RP
Ostrowski
Jiping
J
Tang
John H
JH
Zhang
D000818:Animals; D004195:Disease Models, Animal; D006931:Hyperbaric Oxygenation; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000201:enzymology* / Q000503:physiopathology / Q000628:therapy; D015854:Up-Regulation
D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases