Short-Term Administration of a New Free Radical Scavenger, Edaravone, Is More Effective Than its Long-Term Administration for the Treatment of Neonatal Hypoxic–Ischemic Encephalopathy

Abstract

Background and Purpose— Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a new free radical scavenger that is used for the treatment of adult acute cerebral infarction in Japan. We examined the effect of edaravone on the optimal duration of treatment, the long-term effect on the brain, and the effect on learning and memory disability in a rat model of neonatal hypoxic–ischemic encephalopathy. Methods— Seven-day-old Wistar rats were subjected to left common carotid artery ligation then 2 hours of hypoxic–ischemic insult or sham operation. Edaravone was administered intraperitoneally (9 mg/kg) after hypoxic–ischemic insult every 24 hours for 2, 5, or 10 consecutive days. The neuroprotective effect of edaravone was evaluated by behavioral test and histological analysis. Results— Two-day treatment with edaravone significantly gave protection to the learning and memory capability, as well as morphological recovery compared with control rats. Five-day treatment showed morphological improvement but no behavioral improvement. In contrast, 10-day treatment did not show either morphological or behavior improvement. Conclusions— These findings indicate that edaravone is a promising candidate as a treatment of choice for neonatal hypoxic–ischemic encephalopathy, when its use is limited to the acute phase after hypoxia–ischemia.