Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are increased following acute brain ischemia. These species have been associated with secondary injury that amplifies the magnitude of final neuronal damage. Work with both biochemical analyses and transgenic mice has shown that ROS/RNS production persists for many hours after the initial insult. This offers a potential therapeutic window for pharmacologic intervention of clinical relevance. Several classes of pharmacologic mimetics of superoxide dismutase/catalase have been synthesized. Evaluation of these catalytic antioxidants in laboratory models of acute brain injury has shown both robust neuroprotection and a prolonged therapeutic window at doses apparently devoid of neurotoxicity. (c) 2002 Prous Science. All rights reserved.