Background. Little is known about the induction of functional and brain structural reorganization in hemiplegic cerebral palsy (HCP) by constraint-induced movement therapy (CIMT). Objective. We aimed to explore the specific molecular mechanism of functional and structural plasticity related to CIMT in HCP. Methods. The mice were divided into a control group and HCP groups with different interventions (unconstraint-induced movement therapy [UNCIMT], CIMT or siRNA-Nogo-A [SN] treatment): the HCP, HCP+UNCIMT, HCP+CIMT, HCP+SN, and HCP+SN+CIMT groups. Rotarod and front-limb suspension tests, immunohistochemistry, Golgi-Cox staining, transmission electron microscopy, and Western blot analyses were applied to measure motor function, neurons and neurofilament density, dendrites/axon areas, myelin integrity, and Nogo-A/NgR/RhoA/ROCK expression in the motor cortex. Results. The mice in the HCP+CIMT group had better motor function, greater neurons and neurofilament density, dendrites/axon areas, myelin integrity, and lower Nogo-A/NgR/RhoA/ROCK expression in the motor cortex than the HCP and HCP+UNCIMT groups (P < .05). Moreover, the expression of Nogo-A/NgR/RhoA/ROCK, the improvement of neural remodeling and motor function of mice in the HCP+SN group were similar to those in the HCP+CIMT group (P > .05). The neural remodeling and motor function of the HCP+SN+CIMT group were significantly greater than those in the HCP+SN and HCP+CIMT groups (P < .05). Motor function were positively correlated with the density of neurons (r = 0.450 and 0.309, respectively; P < .05) and neurofilament (r = 0.717 and 0.567, respectively; P < .05). Conclusions. CIMT might promote the remodeling of neurons, neurofilament, dendrites/axon areas, and myelin in the motor cortex by partially inhibiting the Nogo-A/NgR/RhoA/ROCK pathway, thereby promoting the improvement of motor function in HCP mice.

中文翻译：

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约束诱导运动疗法通过克服偏瘫脑瘫小鼠的 Nogo-A/NgR/RhoA/ROCK 信号促进神经重构和功能重组

背景。关于通过约束诱导运动疗法 (CIMT) 诱导偏瘫脑瘫 (HCP) 的功能和大脑结构重组知之甚少。客观的。我们旨在探索 HCP 中与 CIMT 相关的功能和结构可塑性的具体分子机制。方法。将小鼠分为对照组和具有不同干预措施的 HCP 组（无约束诱导运动治疗 [UNCIMT]、CIMT 或 siRNA-Nogo-A [SN] 治疗）：HCP、HCP+UNCIMT、HCP+CIMT、HCP+ SN 和 HCP+SN+CIMT 组。旋转棒和前肢悬吊试验、免疫组织化学、高尔基-考克斯染色、透射电子显微镜和蛋白质印迹分析用于测量运动功能、神经元和神经丝密度、树突/轴突面积、髓鞘完整性、和 Nogo-A/NgR/RhoA/ROCK 在运动皮层中的表达。结果。与HCP和HCP+UNCIMT相比，HCP+CIMT组小鼠的运动功能更好，神经元和神经丝密度更大，树突/轴突面积更大，髓鞘完整，运动皮层Nogo-A/NgR/RhoA/ROCK表达更低组（P < .05）。此外，HCP+SN组Nogo-A/NgR/RhoA/ROCK的表达、神经重构和运动功能的改善与HCP+CIMT组相似（P > .05）。HCP+SN+CIMT 组的神经重构和运动功能显着高于 HCP+SN 和 HCP+CIMT 组（P < .05）。运动功能与神经元密度（分别为 r = 0.450 和 0.309；P < .05）和神经丝（分别为 r = 0.717 和 0.567；P < .05）呈正相关。结论。