Edaravone (MCI-186) scavenges reactive oxygen species and ameliorates tissue damage in the murine spinal cord injury model.
The present study evaluated the effect of the free radical scavenger edaravone on lesion volume and neurological dysfunction after spinal cord injury (SCI) in mice, and investigated its protective effects on superoxide generation. Female C57BL/6 mice were subjected to SCI using a pneumatic impact device and were treated with 3 mg/kg of edaravone or vehicle 30 minutes before the insult. Motor functions were quantitatively evaluated. Lesion volume was assessed by Dohrmann's two-cone method after one week. In situ detection of superoxide in the injured cord was carried out using the superoxide-sensitive dye dihydroethidium (DHE) staining technique. Pretreatment with edaravone significantly improved motor dysfunction and reduced the lesion volume to about 63% of the control (p < 0.05). Semi-quantitative measurements of red fluorescence emitted from DHE revealed that the superoxide concentration increased in the lesion periphery at 1 and 3 hours after the insult, and that pretreatment with edaravone significantly inhibited the increase of superoxide concentration in the lesion periphery at both time points (p < 0.0001). Double staining with DHE and monoclonal antibody against MAP2 showed that most cells positive for DHE were also positive for MAP2. These findings suggest that edaravone ameliorates tissue damage by scavenging reactive oxygen species, especially in the neurons, after SCI.
Aoyama
Takeshi
T
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan. taoya@sirius.ocn.ne.jp
Hida
Kazutoshi
K
Kuroda
Satoshi
S
Seki
Toshitaka
T
Yano
Shunsuke
S
Shichinohe
Hideo
H
Iwasaki
Yoshinobu
Y
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D000077553:Edaravone; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006614:Hindlimb / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011292:Premedication; D017382:Reactive Oxygen Species / Q000032:analysis*; D020127:Recovery of Function; D013116:Spinal Cord / Q000737:chemistry / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D013481:Superoxides / Q000032:analysis
D016166:Free Radical Scavengers; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013481:Superoxides; D000077553:Edaravone; D000983:Antipyrine