Constraint-Induced Movement Therapy Promotes Neural Remodeling and Functional Reorganization by Overcoming Nogo-A/NgR/RhoA/ROCK Signals in Hemiplegic Cerebral Palsy Mice

Abstract

<i>Background</i>. Little is known about the induction of functional and brain structural reorganization in hemiplegic cerebral palsy (HCP) by constraint-induced movement therapy (CIMT). <i>Objective</i>. We aimed to explore the specific molecular mechanism of functional and structural plasticity related to CIMT in HCP. <i>Methods</i>. 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. <i>Results</i>. 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 (<i>P</i> < .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 (<i>P</i> > .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 (<i>P</i> < .05). Motor function were positively correlated with the density of neurons (<i>r</i> = 0.450 and 0.309, respectively; <i>P</i> < .05) and neurofilament (<i>r</i> = 0.717 and 0.567, respectively; <i>P</i> < .05). <i>Conclusions</i>. 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.