title: Therapeutic time window for edaravone treatment of traumatic brain injury in mice.
abstract: Traumatic brain injury (TBI) is a major cause of death and disability in young people. No effective therapy is available to ameliorate its damaging effects. Our aim was to investigate the optimal therapeutic time window of edaravone, a free radical scavenger which is currently used in Japan. We also determined the temporal profile of reactive oxygen species (ROS) production, oxidative stress, and neuronal death. Male C57Bl/6 mice were subjected to a controlled cortical impact (CCI). Edaravone (3.0 mg/kg), or vehicle, was administered intravenously at 0, 3, or 6 hours following CCI. The production of superoxide radicals (O2 (∙-)) as a marker of ROS, of nitrotyrosine (NT) as an indicator of oxidative stress, and neuronal death were measured for 24 hours following CCI. Superoxide radical production was clearly evident 3 hours after CCI, with oxidative stress and neuronal cell death becoming apparent after 6 hours. Edaravone administration after CCI resulted in a significant reduction in the injury volume and oxidative stress, particularly at the 3-hour time point. Moreover, the greatest decrease in O2 (∙-) levels was observed when edaravone was administered 3 hours following CCI. These findings suggest that edaravone could prove clinically useful to ameliorate the devastating effects of TBI.
authors.affiliation: Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ohtaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Dohi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Tsumuraya
authors.forename: Dandan
authors.initials: D
authors.lastname: Song
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kiriyama
authors.forename: Kazue
authors.initials: K
authors.lastname: Satoh
authors.forename: Ai
authors.initials: A
authors.lastname: Shimizu
authors.forename: Tohru
authors.initials: T
authors.lastname: Aruga
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D007564:Japan; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D000077553:Edaravone; D000983:Antipyrine