title: Edaravone attenuates brain edema and neurologic deficits in a rat model of acute intracerebral hemorrhage.
abstract: 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.
authors: Department of Neurobiology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan. tanakamu@kms.ac.jp
authors: Takehiro
authors: T
authors: Nakamura
authors: Yasuhiro
authors: Y
authors: Kuroda
authors: Susumu
authors: S
authors: Yamashita
authors: Xia
authors: X
authors: Zhang
authors: Osamu
authors: O
authors: Miyamoto
authors: Takashi
authors: T
authors: Tamiya
authors: Seigo
authors: S
authors: Nagao
authors: Guohua
authors: G
authors: Xi
authors: Richard F
authors: RF
authors: Keep
authors: Toshifumi
authors: T
authors: Itano
mesh_terms: 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
chemical_list: D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D014867:Water; D000077553:Edaravone; D000983:Antipyrine