Li Chao, Wen HongMei, Wang QingMei, Zhang ChanJuan, Jiang Li, Dou ZuLin, Luo Xun, Zeng JinSheng
From the Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China (CL, HMW, CJZ, LJ, ZLD); Stroke Biological Recovery Laboratory, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, Massachusetts (QMW); Department of Rehabilitation Medicine, The Fourth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China (XL); and Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China (JSZ).
Am J Phys Med Rehabil. 2015 Dec;94(12):1083-94. doi: 10.1097/PHM.0000000000000339.
The aim of this study was to test the hypothesis that exercise training promotes motor recovery after stroke by facilitating axonal remodeling via inhibition of the Nogo-A/NgR1 and Rho-A pathway.
A distal middle cerebral artery occlusion model was generated in stroke-prone renovascular hypertensive rats. Stroke-prone renovascular hypertensive rats were randomly divided into a control group, an exercise training group, and a sham group. Motor function was measured using the grip strength test. Axon and myelin remodeling markers, growth-associated protein 43, myelin basic protein, Tau, and amyloid precursor protein were detected by immunofluorescence. The expression of Nogo-A, NgR1, and Rho-A was demonstrated by immunofluorescence and Western blotting in the peri-infarction area at 7, 14, 28, and 52 days after distal middle cerebral artery occlusion.
Grip strength was higher in the exercise training group (P < 0.05). Exercise training increased the expression of growth-associated protein 43, myelin basic protein (at 7, 14, and 28 days), and Tau (at 7 and 14 days), and decreased the expression of axonal damage amyloid precursor protein (at 7 and 14 days), compared with the control group. The protein levels of Nogo-A (at 7 and 14 days), NgR1 (at 7, 14, and 28 days), and Rho-A (at 14 and 28 days) were reduced after exercise training.
Exercise training promotes axonal recovery, which is associated with functional improvement after cerebral infarction. Down-regulation of the Nogo-A/NgR1/Rho-A may mediate the axonal remodeling induced by exercise training.
本研究旨在验证以下假设，即运动训练通过抑制Nogo-A/NgR1和Rho-A信号通路促进轴突重塑，从而促进中风后运动功能恢复。
在易患中风的肾血管性高血压大鼠中建立大脑中动脉远端闭塞模型。将易患中风的肾血管性高血压大鼠随机分为对照组、运动训练组和假手术组。采用握力测试评估运动功能。通过免疫荧光检测轴突和髓鞘重塑标志物、生长相关蛋白43、髓鞘碱性蛋白、Tau蛋白和淀粉样前体蛋白。在大脑中动脉远端闭塞后7天、14天、28天和52天，通过免疫荧光和蛋白质印迹法检测梗死灶周围区域Nogo-A、NgR1和Rho-A的表达。
运动训练组的握力更高（P<0.05）。与对照组相比，运动训练增加了生长相关蛋白43、髓鞘碱性蛋白（在7天、14天和28天）和Tau蛋白（在7天和14天）的表达，并降低了轴突损伤标志物淀粉样前体蛋白（在7天和14天）的表达。运动训练后，Nogo-A（在7天和14天）、NgR1（在7天、14天和28天）和Rho-A（在14天和28天）的蛋白水平降低。
运动训练促进轴突恢复，这与脑梗死后功能改善相关。Nogo-A/NgR1/Rho-A信号通路的下调可能介导了运动训练诱导的轴突重塑。
