Role of NADPH oxidase in the brain injury of intracerebral hemorrhage.
The major risk factors for intracerebral hemorrhage (ICH) are hypertension and aging. A fundamental mechanism for hypertension- and aging-induced vascular injury is oxidative stress. We hypothesize that oxidative stress has a crucial role in ICH. To test our hypothesis, we used bacterial collagenase to produce ICH in wild-type C57BL/6 and gp91phox knockout (gp91phox KO) mice (deficient in gp91phox subunit of the superoxide-producing enzyme NADPH oxidase). All animals were studied at 20-35 weeks of age, resembling an older patient population. We found that collagenase produced less bleeding in gp91phox KO mice than wild-type mice. Total oxidative product was lower in gp91phox KO mice than in wild-type mice, both under basal conditions and after ICH. Consistent with the ICH volume, brain edema formation, neurological deficit and a high mortality rate was noted in wild-type but not in gp91phox KO mice. This ICH-induced brain injury in wild-type mice is associated with enhanced expression of the gp91phox subunit of NADPH oxidase. In conclusion, the oxidative stress resulting from activation of NADPH oxidase contributes to ICH induced by collagenase and promotes brain injury.
Tang
Jiping
J
Department of Molecular and Cellular Physiology, Lousiana State University Health Science Center, Shrevenport, Louisiana, USA.
Liu
Jun
J
Zhou
Changman
C
Ostanin
Dmitry
D
Grisham
Matthew B
MB
Neil Granger
D
D
Zhang
John H
JH
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001921:Brain / Q000473:pathology*; D001929:Brain Edema / Q000473:pathology; D002536:Cerebral Arteries / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D017364:Collagenases; D005838:Genotype; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000503:physiopathology; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism
D001786:Blood Glucose; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D017364:Collagenases