Ishii Hideaki, Petrenko Andrey B, Sasaki Mika, Satoh Yukio, Kamiya Yoshinori, Tobita Toshiyuki, Furutani Kenta, Matsuhashi Mari, Kohno Tatsuro, Baba Hiroshi
Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahi-machi, Chuo-ku, Niigata 951-8510, Japan.
Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahi-machi, Chuo-ku, Niigata 951-8510, Japan; Department of Anesthesiology, Saiseikai Niigata Daini Hospital, 280-7 Teraji, Nishi-ku, Niigata 950-1104, Japan.
Brain Res. 2018 Mar 1;1682:24-35. doi: 10.1016/j.brainres.2017.12.035. Epub 2017 Dec 30.
We used a multimodal approach to evaluate the effects of edaravone in a rat model of spinal cord injury (SCI). SCI was induced by extradural compression of thoracic spinal cord. In experiment 1, 30 min prior to compression, rats received a 3 mg/kg intravenous bolus of edaravone followed by a maintenance infusion of 1 (low-dose), 3 (moderate-dose), or 10 (high-dose) mg/kg/h edaravone. Although both moderate- and high-dose edaravone regimens promoted recovery of spinal motor-evoked potentials (MEPs) at 2 h post-SCI, the effect of the moderate dose was more pronounced. In experiment 2, moderate-dose edaravone was administered 30 min prior to compression, at the start of compression, or 10 min after decompression. Although both preemptive and coincident administration resulted in significantly improved spinal MEPs at 2 h post-SCI, the effect of preemptive administration was more pronounced. A moderate dose of edaravone resulted in significant attenuation of lipid peroxidation, as evidenced by lower concentrations of the free radical malonyldialdehyde in the spinal cord 3 h post-SCI. Malonyldialdehyde levels in the high-dose edaravone group were not reduced. Both moderate- and high-dose edaravone resulted in significant functional improvements, evidenced by better Basso-Beattie-Bresnahan (BBB) scores and better performance on an inclined plane during an 8 week period post-SCI. Both moderate- and high-dose edaravone significantly attenuated neuronal loss in the spinal cord at 8 weeks post-SCI, as evidenced by quantitative immunohistochemical analysis of NeuN-positive cells. In conclusion, early administration of a moderate dose of edaravone minimized the negative consequences of SCI and facilitated functional recovery.
我们采用多模态方法评估依达拉奉在大鼠脊髓损伤（SCI）模型中的作用。通过胸段脊髓硬膜外压迫诱导脊髓损伤。在实验1中，压迫前30分钟，大鼠接受3mg/kg依达拉奉静脉推注，随后以1（低剂量）、3（中剂量）或10（高剂量）mg/kg/h的速度持续输注依达拉奉。虽然中剂量和高剂量依达拉奉方案均能促进脊髓损伤后2小时脊髓运动诱发电位（MEP）的恢复，但中剂量的效果更显著。在实验2中，在压迫前30分钟、压迫开始时或减压后10分钟给予中剂量依达拉奉。虽然预防性给药和同时给药均能使脊髓损伤后2小时脊髓MEP显著改善，但预防性给药的效果更显著。中剂量依达拉奉可显著减轻脂质过氧化，脊髓损伤后3小时脊髓中自由基丙二醛浓度降低证明了这一点。高剂量依达拉奉组的丙二醛水平未降低。中剂量和高剂量依达拉奉均能显著改善功能，脊髓损伤后8周内Basso-Beattie-Bresnahan（BBB）评分更高以及在斜面上表现更好证明了这一点。通过对NeuN阳性细胞的定量免疫组织化学分析证明，中剂量和高剂量依达拉奉均能在脊髓损伤后8周时显著减轻脊髓神经元丢失。总之，早期给予中剂量依达拉奉可将脊髓损伤的负面后果降至最低并促进功能恢复。
