Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Biomed Res Int. 2013;2013:379206. doi: 10.1155/2013/379206. Epub 2013 Apr 10.
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.
创伤性脑损伤（TBI）是年轻人死亡和残疾的主要原因。目前尚无有效的治疗方法来减轻其破坏性影响。我们的目的是研究自由基清除剂依达拉奉的最佳治疗时间窗，依达拉奉目前在日本使用。我们还确定了活性氧（ROS）产生、氧化应激和神经元死亡的时间进程。雄性 C57Bl/6 小鼠接受皮质撞击（CCI）。依达拉奉（3.0mg/kg）或载体在 CCI 后 0、3 或 6 小时静脉给药。CCI 后 24 小时测量超氧自由基（O2（∙-））作为 ROS 的标志物、硝基酪氨酸（NT）作为氧化应激的指标以及神经元死亡。CCI 后 3 小时超氧自由基产生明显，CCI 后 6 小时出现氧化应激和神经元细胞死亡。CCI 后给予依达拉奉可显著减少损伤体积和氧化应激，特别是在 3 小时时间点。此外，当依达拉奉在 CCI 后 3 小时给予时，O2（∙-）水平下降最大。这些发现表明依达拉奉可能在临床上有助于减轻 TBI 的破坏性影响。
