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lüll Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury Yoshida H; Yanai H; Namiki Y; Fukatsu-Sasaki K; Furutani N; Tada NCNS Drug Rev 2006[Spr]; 12 (1): 9-20Recanalization and neuroprotection have been mainly targeted for the specific treatment of acute ischemic stroke. Free radicals play a crucial role in brain ischemic injury by exacerbating membrane damage through peroxidation of unsaturated fatty acids of cell membrane, leading to neuronal death and brain edema. Free radicals have been implicated in stroke pathophysiology as pivotal contributors to cell injury. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a novel potent free radical scavenger that has been clinically used to reduce the neuronal damage following ischemic stroke. Edaravone exerts neuroprotective effects by inhibiting endothelial injury and by ameliorating neuronal damage in brain ischemia. Edaravone provides the desirable features of NOS: it increases eNOS (beneficial NOS for rescuing ischemic stroke) and decreases nNOS and iNOS (detrimental NOS). Post- reperfusion brain edema and hemorrhagic events induced by thrombolytic therapy may be reduced by edaravone pretreatment. Increased productions of superoxide and NO in the brain after reperfusion and a concomitant surge in oxygen free radicals with increased NO during recirculation lead to formation of peroxynitrite, a superpotent radical. Edaravone, which inhibits oxidation and enhances NO production derived from increased eNOS expression, may improve and conserve cerebral blood flow without peroxynitrite generation during reperfusion. Clinical experience with edaravone suggests that this drug has a wide therapeutic time window. The combination therapy (a thrombolytic plus edaravone) is likely to target brain edema, reduce stroke death and improve the recovery from neurological deficits in stoke patients.|*Free Radical Scavengers[MESH]|Animals[MESH]|Antipyrine/*analogs & derivatives/pharmacology/therapeutic use[MESH]|Cerebrovascular Disorders/classification/*drug therapy[MESH]|Edaravone[MESH]|Humans[MESH]|Models, Biological[MESH]|Neuroprotective Agents/pharmacology/*therapeutic use[MESH]|Nitric Oxide/metabolism[MESH] |