Free radical generation in germinal matrix hemorrhage

Abstract

Germinal matrix hemorrhage‐Intraventricular hemorrhage (GMH‐IVH) is a major complication of prematurity. In adult animal model, intracerebral hemorrhage is attended by free radical generation resulting from activation of NADPH oxidase, which contributes to brain injuries. Therefore, we hypothesized that there might be greater generation of reactive oxygen species (ROS) in brain with IVH than controls and that suppression of NADPH oxidase might attenuate free radical formation. We tested our hypotheses in a rabbit pup model. We delivered pups prematurely and induced IVH by producing intracranial hypotension with IP glycerol at 2h age. We measured production of O2. ‐ and H2O2 in the periventricular and the cerebral cortical area at 6h postnatal age. To determine the source of free radical generation, we used inhibitors for NADPH oxidase (apocynin), xanthine oxidase, COX‐2 or NO synthase. We found that O2. ‐ and H2O2 generation were significantly greater in both the periventricular area and cortex of pups with IVH than controls (P<0.05). Only apocynin inhibited ROS generation in both brain areas (P<0.05). Our data suggest that free radicals are generated more in the periventricular area than in the cortical mantle in IVH and that the activation of NAPDH oxidase is the predominant mechanism of oxidative stress. Suppression of ROS production by NADPH oxidase inhibitor might reduce brain injuries in premature infants.