Constraint-induced Movement Therapy Promotes Neural Remodeling And Functional Reorganization By Regulating C-Jun/Micro182-5P/Nogo-A In Hemiplegic Cerebral Palsy Mice

Objective: Cerebral palsy(CP)is a disorder that characterized by abnormal tone,posture and movement,the incidence of CP is 2–3 per 1,000 live births.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 [n CIMT],CIMT,lenti-c-Jun[LC] and sh RNA-c-Jun[SC] treatment): n CIMT,HCP+CIMT,HCP+ LC +n CIMT,HCP+ LC +CIMT,HCP+ SC +CIMT groups.Beam walking test and Grip tests,immunohistochemistry,Golgi-Cox staining,transmission electron microscopy,and Quantitative Real-time PCR were applied to measure motor function,neurons and neurofilament density,dendrites/axon areas,myelin integrity,and c-Jun/mi R-182-5p/Nogo-A 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,lower Nogo-A expression and higher c-Jun/mi R-182-5p expression than the HCP+n CIMT groups(P <0.05).Moreover,the expression of c-Jun/mi R-182-5p,the improvement of neural remodeling and motor function of mice in the HCP+lenti-c-Jun+n CIMT group were similar to those in the HCP+CIMT group(P >0.05).The neural remodeling and motor function of the HCP+lenti-c-Jun+CIMT group were significantly greater than those in the HCP+lenti-c-Jun+CIMT and HCP+CIMT groups(P <0.05).Conclusion : CIMT might promote the remodeling of neurons,neurofilament,dendrites/axon areas,and myelin in the motor cortex by partially inhibiting the c-Jun/mi R-182-5p/Nogo-A pathway,thereby promoting the improvement of motor function in HCP mice.