Role of NADPH oxidase in the brain injury of intracerebral hemorrhage

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Abstract
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 andgp91phoxknockout (gp91phoxKO) mice (deficient in gp91phoxsubunit 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 ingp91phoxKO mice than wild‐type mice. Total oxidative product was lower ingp91phoxKO 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 ingp91phoxKO mice. This ICH‐induced brain injury in wild‐type mice is associated with enhanced expression of thegp91phoxsubunit of NADPH oxidase. In conclusion, the oxidative stress resulting from activation of NADPH oxidase contributes to ICH induced by collagenase and promotes brain injury.