Free radical scavenger edaravone produces robust neuroprotection in a rat model of spinal cord injury
Free radical scavenger edaravone produces robust neuroprotection in a rat model of spinal cord injury
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DOI：
10.1016/j.brainres.2017.12.035
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发表时间：
2018-03-01
期刊：
影响因子：
2.9
通讯作者：
Baba, Hiroshi
中科院分区：
文献类型：
--
作者：
Ishii, Hideaki;Petrenko, Andrey B.;Baba, Hiroshi
我们采用多模式方法评估依达拉奉在大鼠脊髓损伤 (SCI) 模型中的作用。 SCI 是由于胸脊髓硬膜外受压所致。在实验 1 中，压迫前 30 分钟，大鼠接受 3 mg/kg 依达拉奉静脉推注，随后维持输注 1（低剂量）、3（中剂量）或 10（高剂量）mg/kg/h 依达拉奉。尽管中剂量和高剂量依达拉奉方案均促进 SCI 后 2 小时脊髓运动诱发电位 (MEP) 的恢复，但中剂量的效果更为明显。在实验2中，在加压前30分钟、加压开始时或减压后10分钟给予中等剂量的依达拉奉。尽管抢先给药和同步给药均可显着改善 SCI 后 2 小时的脊髓 MEP，但抢先给药的效果更为明显。中等剂量的依达拉奉可显着减弱脂质过氧化作用，SCI 后 3 小时脊髓中自由基丙二醛浓度较低即可证明这一点。高剂量依达拉奉组的丙二醛水平没有降低。中剂量和高剂量的依达拉奉均带来了显着的功能改善，SCI 后 8 周内更好的 Basso-Beattie-Bresnahan (BBB) 分数和更好的斜面表现就证明了这一点。 NeuN 阳性细胞的定量免疫组织化学分析证明，中剂量和高剂量的依达拉奉均可显着减轻 SCI 后 8 周脊髓中的神经元损失。总之，早期给予中等剂量的依达拉奉可以最大限度地减少 SCI 的负面后果并促进功能恢复。 (C) 2017 Elsevier B.V. 保留所有权利。
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. (C) 2017 Elsevier B.V. All rights reserved.