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.
OBJECTIVE
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.
Noor
Jesmin I
JI
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Ikeda
Tomoaki
T
Mishima
Kenichi
K
Aoo
Naoya
N
Ohta
Sumie
S
Egashira
Nobuaki
N
Iwasaki
Katsunori
K
Fujiwara
Michihiro
M
Ikenoue
Tsuyomu
T
D000818:Animals; D000831:Animals, Newborn; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy*; D018782:Maze Learning; D015233:Models, Statistical; D018696:Neuroprotective Agents / Q000008:administration & dosage; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D000077553:Edaravone; D000983:Antipyrine