title: [Neuroprotective therapy for the treatment of acute ischemic stroke].
abstract: Following cerebral ischemia, various biochemical reactions are provoked in a stepwise manner leading neuronal cells to ischemic death. The prevention of these biochemical reactions may exert neuroprotective actions and consequently reduce the magnitude of ischemic cerebral injury. On the basis of such a view, numerous neuroprotective drugs have been developed during the last decade. Quite a few drugs were found effective in reducing the infarct volume in experimental studies, and more than 15 of them were subjected to clinical phase III trials to see a therapeutic effectiveness. However, the results of phase III trials were disappointing in the majority drugs. Only three drugs, nicaravene, ebselen and edaravone, all radical scavengers, were judged effective by small-sized trials with a wide therapeutic window, 48-72 hours after stroke, in Japan. The fact suggests that a one-point prevention of biochemical reactions by single drug is unable to rescue ischemic neuronal cells. Ischemic insult causes damages of vascular wall including the endothelium which play an important role in the development of hemorrhagic changes or cerebral edema. Vascular protection is considered as important as neuroprotection in treatment of clinical stroke. Mild hypothermia has neuroprotective and vascular protective actions and hence may be more effective than neuroprotective drugs for the treatment of stroke. The prevention of fever, which often occurs in severe stroke, may exert the similar effect as hypothermia in neuroprotection. Neuroprotective therapy in the future should proceed toward the simultaneous protections of neurons and vessels using combination of multiple drugs.
authors.forename: H
authors.initials: H
authors.lastname: Naritomi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D007036:Hypothermia, Induced; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020521:Stroke / Q000628:therapy*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D009536:Niacinamide; D000077553:Edaravone; D000983:Antipyrine; C042625:nicaraven