Neuroprotective effects of the free radical scavenger Edaravone (MCI-186) in mice permanent focal brain ischemia.
The present study was aimed to evaluate the effect of the free radical scavenger Edaravone on infarct volume due to permanent MCA occlusion in mice and, if so, to elucidate the mechanism of its neuroprotective effects. Male Balb/c mice were subjected to permanent middle cerebral artery occlusion and were treated with 3.0 mg/kg of Edaravone or vehicle 30 min before ischemia. Infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) method after 24 h. Furthermore, in situ detection of superoxide in the ipsilateral neocortex was carried out using the superoxide-sensitive dye dihydroethidium (DHE) staining technique. Pretreatment with 3.0 mg/kg of Edaravone ameliorated the tissue damage in the infarct rim and significantly reduced infarct volume to about 77% of the control (p<0.05). Semi-quantitative measurement of red fluorescence emitted from DHE revealed that the superoxide increased in the ischemic core at 1 h after the onset of ischemia and extended towards the infarct rim at 3 and 6 h, and that pretreatment with 3.0 mg/kg of Edaravone significantly inhibited the increase of superoxide in the infarct rim at 3 and 6 h (p<0.01). Double staining with DHE and monoclonal antibody against NeuN showed that the majority of the nuclei positive for DHE were also positive for NeuN. These findings suggest that Edaravone salvages the boundary zone of infarct by scavenging reactive oxygen species especially in the neurons during permanent focal cerebral ischemia.
Shichinohe
Hideo
H
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Kuroda
Satoshi
S
Yasuda
Hiroshi
H
Ishikawa
Tatsuya
T
Iwai
Masaru
M
Horiuchi
Masatsugu
M
Iwasaki
Yoshinobu
Y
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins; D000077553:Edaravone; D004996:Ethidium / Q000031:analogs & derivatives*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D004268:DNA-Binding Proteins; D016166:Free Radical Scavengers; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D018696:Neuroprotective Agents; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; C067883:dihydroethidium; D013481:Superoxides; D004996:Ethidium; D000077553:Edaravone; D000983:Antipyrine