Edaravone attenuates brain edema and neurologic deficits in a rat model of acute intracerebral hemorrhage.
OBJECTIVE
Our previous studies have demonstrated that oxidative DNA injury occurs in the brain after intracerebral hemorrhage (ICH). We therefore examined whether edaravone, a free-radical scavenger, could reduce ICH-induced brain injury.


METHODS
These experiments used pentobarbital-anesthetized, male Sprague-Dawley rats that received an infusion of either 100 microL autologous whole blood (ICH), FeCl(2), or thrombin into the right basal ganglia. The rats were humanely killed 24 hours later. There were 4 sets of experiments. In the first, the dose-dependent effects of edaravone on ICH-induced brain injury were examined by measuring brain edema and neurologic deficits. In the second set, apurinic/apyrimidinic abasic sites and 8-hydroxyl-2'-deoxyguanosine, which are hallmarks of DNA oxidation, were investigated after treatment for ICH. In the third, the effect of delayed treatment with edaravone on ICH-induced injury was determined, whereas the fourth examined the effects of edaravone on iron- and thrombin-induced brain injury.


RESULTS
Systemic administration of edaravone immediately or 2 hours after ICH reduced brain water content 24 hours after ICH compared with vehicle (P<0.05). Edaravone treatment immediately or 2 hours after ICH also ameliorated neurologic deficits (P<0.05). Edaravone also attenuated ICH-induced changes in apurinic/apyrimidinic abasic sites and 8-hydroxyl-2'-deoxyguanosine and reduced iron- and thrombin-induced brain injury.


CONCLUSIONS
Edaravone attenuates ICH-induced brain edema, neurologic deficits, and oxidative injury. It also reduces iron- and thrombin-induced brain injury. These results suggest that edaravone is a potential therapeutic agent for ICH.
Nakamura
Takehiro
T
Department of Neurobiology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan. tanakamu@kms.ac.jp
Kuroda
Yasuhiro
Y
Yamashita
Susumu
S
Zhang
Xia
X
Miyamoto
Osamu
O
Tamiya
Takashi
T
Nagao
Seigo
S
Xi
Guohua
G
Keep
Richard F
RF
Itano
Toshifumi
T
D000208:Acute Disease; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000188:drug therapy*; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water / Q000378:metabolism
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D014867:Water; D000077553:Edaravone; D000983:Antipyrine