Role of free radical reactions in ischemic brain injury.
Free radical reactions figure prominently in ischemic brain injury by inducing lipid peroxidation and damage to DNA and proteins. Several research areas have attracted recent attention, including the pathophysiological roles of nitric oxide (NO) radical and the peroxynitrite anion, formed by the reaction of NO with superoxide; the vulnerability of mitochondria to oxidative injury; and the relevance of both vascular sites (e.g., endothelial injury, neutrophil activation and secretion of radical species) and parenchymal sites of radical-mediated injury. A variety of biomarkers have been validated for the detection of radical products and radical-mediated injury to lipids, DNA and proteins. Pharmacological advances in antioxidant therapy include the development of novel nitrone-based spin trap agents with neuroprotective properties. Human serum albumin in moderate-to-high doses has been shown to be strikingly neuroprotective in brain ischemia, and its effects may be mediated by antioxidant mechanisms. The use of transgenic and knockout mutant mice has proved enormously useful in elucidating oxidant injury mechanisms in cerebral ischemia.
Ginsberg
M D
MD
Cerebral Vascular Disease Research Center, Dept. of Neurology, University of Miami School of Medicine, Miami, Florida 33101, USA.