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

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.

[Effects of transcutaneous electrical nerve stimulation on motor function in ambulant children with spastic cerebral palsy: a randomized trial].

OBJECTIVE: To investigate the effects of transcutaneous electrical nerve stimulation (TENS) on motor function in children with spastic cerebral palsy (CP). METHODS: After signing the informed consent, 78 children with CP, aged 45.6 +/- 8.5 months (36 to 58 months), were randomly divided into a TENS group (n = 40) and a control group (n = 38). All the subjects received standardized functional exercise program. In TENS group, 2 TENS devices were used and the surface electrodes were applied on the spastic musculotendinous and antagonist muscles in the affected lower extremity. TENS lasted for 20 min per session, 5 days weekly for 6 weeks. After 6 weeks, the functional exercise program was applied by the caregivers. Demographic data were recorded, including age, gender, number of the hemiplegic and diplegic CP, level of gross motor function classification system (GMFCS). Clinical assessments included the composite spasticity scale (CSS), D and E dimensions of the Gross Motor Function Measure (GMFM), and walking velocity was determined before treatment and at 6, 12 and 24 weeks after treatment. RESULTS: No statistically significant differences were found in age, gender, number of the hemiplegic and diplegic CP, level of GMFCS, as well as clinical assessments (CSS, GMFM and walking velocity) before treatment between the 2 groups (P > 0.05). All the children showed a reduction of spasticity (CSS) after 6, 12 and 24 weeks of treatment (P < 0.05). When compared with the results obtained before treatment, the improvement of standing and walking (GMFM), walking velocity was statistically significant after 6, 12 and 24 weeks of treatment (P < 0.05). Furthermore, the differences of CSS, GMFM and walking velocity between the two groups at 6, 12 and 24 weeks examination were also statistically significant (after 24 weeks of treatment: t value was 8.96, 3.14 and 2.35, P < 0.05, respectively). CONCLUSION: When compared with the control group, 6 weeks of TENS treatment on the affected lower extremity was more effective in terms of reducing spasticity and improving functional performance in standing, walking, and walking velocity in ambulant children with the spastic CP.

[Effects of botulinum toxin guided by electric stimulation on spasticity in ankle plantar flexor of children with cerebral palsy: a randomized trial].

OBJECTIVE: To compare the effects of botulinum toxin A (BTX-A) injection guided by electric stimulation combined with physiotherapy, with physiotherapy only on the spasticity of the ankle plantar flexor in children with cerebral palsy (CP). METHODS: After signing the informed consent, 43 children with CP, aged 52.4 +/- 13.2 months (35 to 82 months), were randomly assigned into 2 groups, (1) BTX-A group (n = 23) treated with BTX-A injection guided by electric stimulation and (2) physiotherapy alone group (n = 20). Children in BTX-A group received injection of HengLi BTX-A in the ankle plantar flexors. A maximum dose of 12 units of BTX-A per kilogram body weight and maximumly 10 units of BTX-A per site were administered. Localization technique was the use of electrical stimulation guidance. Physiotherapy and ankle-foot orthosis were applied to children at 72 hours after injection in BTX-A group and at the time of being recruited into physiotherapy group. Ten days after entering into the study, the program was applied by the parents. Demographic data, including age, gender, number of the spastic lower limbs, affected side (left or right) were recorded. Clinical assessments included the range of passive movement (PROM) measured by goniometer while children maintained the knee extended, modified Ashworth scale (MAS), composite spasticity scale (CSS), D and E dimensions of the Gross Motor Function Measure (GMFM), and walking velocity (WV) was determined before treatment and at 2 weeks, 1, 2, and 3 months after treatment. RESULTS: No statistically significant differences were found in age, gender, number of the spastic lower limbs, affected side, as well as clinical assessments (PROM, MAS, CSS, GMFM and WV) before treatment between the 2 groups (P > 0.05). All the children showed a reduction of spasticity (PROM, MAS and CSS) after 2 weeks, 1, 2, and 3 months of treatment (P < 0.05). When compared with the baseline findings, the improvement of standing and walking (GMFM), walking velocity were statistically significant after 2 weeks, 1, 2, and 3 months of treatment (P < 0.05). Furthermore, the differences of PROM, MAS and CSS between the 2 groups at 2 weeks, 1, 2, and 3 months examination were also statistically significant (after 3 months of treatment: t(PROM) = 6.48, t(MAS) = 9.74, t(CSS) = 9.59; P < 0.05). The difference in GMFM between the 2 groups was statistically significant (t(1M) = 2.20, t(2M) = 3.26, t(3M) = 4.13; P < 0.05) at 1, 2, and 3 months after treatment. The difference of WV between the 2 groups was statistically significant (t(2M) = 2.12, t(3M) = 2.57; P < 0.05) at 2 and 3 months after treatment. CONCLUSION: BTX-A injection guided by electrical stimulation in combination with physiotherapy was more effective than physiotherapy alone in terms of reducing spasticity and improving functional performance in standing, walking, walking pattern and velocity on spasticity in ankle plantar flexors of ambulant children with CP.