Inoue Takahiro, Okamura Misato, Kitahara Mika, Takamatsu Yasuyuki, Sakakima Harutoshi, Maejima Hiroshi
Graduate School of Health Sciences, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo 060-0812, Japan; Japan Society for the Promotion of Science, 5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan.
Graduate School of Health Sciences, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo 060-0812, Japan.
Neuroscience. 2020 Mar 15;430:12-24. doi: 10.1016/j.neuroscience.2020.01.012. Epub 2020 Jan 23.
The objective of this study was to examine the interactive effects of exercise and low-level inhibition of GABA receptors on the recovery of motor function and BDNF expression in the primary motor cortex (M1) of a stroke rat model. Male Sprague-Dawley rats were divided into five groups: sham (SHAM), control (CON), exercise (EX), bicuculline (BIC), and bicuculline plus exercise (BICEX) groups. All rats, except those in the SHAM group, underwent middle cerebral artery occlusion (MCAO) surgery to induce an ischemic stroke. GABA receptor antagonist, bicuculline (0.25 mg/kg, i.p.), was administered to the BIC and BICEX groups. The EX and BICEX groups exercised on a treadmill (11 m/min for 30 min). Each intervention started 3 days after the MCAO surgery and was carried out every day for 2 weeks. Following the intervention, bilateral M1 BDNF mRNA and protein expression levels were assessed using qRT-PCR and ELISA. Marginal recovery was found in the EX and BIC groups, whereas motor function recovery was enhanced with exercise in the presence of BIC administration specifically in the BICEX group. Furthermore, BDNF protein level in the ipsilateral M1 was significantly higher in the BICEX group than in other groups. This study indicated that exercise combined with low-level inhibition of GABA receptors after stroke could facilitate the recovery of motor function accompanied by BDNF upregulation in the ipsilateral M1. Therefore, this study provides a novel insight of pharmacological neuromodulation into stroke rehabilitation.
本研究的目的是探讨运动与低水平抑制GABA受体对中风大鼠模型初级运动皮层（M1）运动功能恢复和脑源性神经营养因子（BDNF）表达的交互作用。雄性Sprague-Dawley大鼠分为五组：假手术组（SHAM）、对照组（CON）、运动组（EX）、荷包牡丹碱组（BIC）和荷包牡丹碱加运动组（BICEX）。除SHAM组大鼠外，其余所有大鼠均接受大脑中动脉闭塞（MCAO）手术以诱导缺血性中风。向BIC组和BICEX组大鼠腹腔注射GABA受体拮抗剂荷包牡丹碱（0.25 mg/kg）。EX组和BICEX组大鼠在跑步机上运动（速度为11 m/min，持续30分钟）。每种干预在MCAO手术后3天开始，每天进行，持续2周。干预后，采用qRT-PCR和ELISA法评估双侧M1区BDNF mRNA和蛋白表达水平。EX组和BIC组发现有轻微恢复，而在给予荷包牡丹碱的情况下，运动可增强运动功能恢复，特别是在BICEX组。此外，BICEX组同侧M1区的BDNF蛋白水平显著高于其他组。本研究表明，中风后运动联合低水平抑制GABA受体可促进运动功能恢复，并伴有同侧M1区BDNF上调。因此，本研究为中风康复的药理神经调节提供了新的见解。
