Effects Of Constraint-Induced Movement Therapy On Neural Reparation And Rho Kinase Expression After Cerebral Ischemia-reperfusion In Rats

ObjectiveAt present,constraint-induced movement therapy(CIMT)is applicated to neurological rehabilitation extensively,confirmed to promote motor recovery after stroke efficiently.The functional reorganization of cerebral cortex with CIMT can complement the function of injured tissues,which has been confirmed by functional magnetic resonance imaging and transcranial magnetic stimulation.There is high plasticity in nervous system and nerve regeneration sereves as a critical part in nervous plasticiy.Rehabilitation training after cerebral infarction has a effect on nerve regeneration,and then influences neural recovery of function.Nerve regeneration consists of the activation of endogenous nerve stem cells and axon anagenesis,which forms the constructive foundation of functional recovery after cerebral infarction.Neuroglia in central nervous system can generate a lot of substance such as Nogo, myelin associated glucoprotein and oligodendrocyte myelin glucoprotein,and they all can inhibit damaged neural axons from axon regenerating.The above-mentioned proteins produce their inhibiting effects by way of combining with the receptor of Nogo and activating Rho kinase.Strornal cell-derived factor-1(SDF-1)has the activiy of chemotatic factor and cell growth factor,produced by bone marrow strornal cells. Western blor analysis has revealed an increase of SDF-1 expression in peri-ischemia cortex of ischemic hemisphere after 3-week CIMT.Furthermore,CIMT promoted motor recovery after stroke efficiently.It has been found that SDF-1/CXCR4 plays a very important role in stem cell mobilization,migration and homing,and SDF-1 facilitates axon anagenesis by inhibiting the activity of Rho kinase.So it can be inferred that CIMT can improve nervous function probably because it can activate endogenous nerve stem cells and facilitate axon anagenesis.However,most of researchs carried out on CIMT today focus on imageology and ethology generally,viewing from the angle of function,and scarcely investigate the effect of CIMT on nerve regeneration after cerebral ischemia at molecular level.To verify the above-mentioned hypothesis,femal SD rats are used to investigate the effect of CIMT on neural reparation after cerebral ischemia -reperfusion injury and Rho kinase expression,so that a new rationale is expect to be produced for clinical theraphy of cerebral infarction.Methods75 Healthy female Sprague-Dawley rats were randomly divided into 3 groups: constraint-induced movement therapy group(CIMT group,n=25),ischemia-reperfusion group(I/R group,n=25)and sham group(n=25).The CIMT group and I/R group were modeled with cerebral ischemia-reperfusion by blocking middle cerebral artery with a nylon thread.The three groups then were divided into 7^th,14^th,21^st,28^th,35^thday execution groups after cerebral ischemia-reperfusion by randomized blocks methods. The cast of the anterior limb on the contralateral side of the ischemia-reperfusion was used in CIMT group from 7^thday after cerebral ischemia-reperfusion.Behavior scores, trapezoid balance bar experiment and Morris water maze experiment were all carried out to evaluate the recovery of neural function at 7^th,14^th,21^st,28^th,35^thday postsurgery respectively.The expression of Rho kinase in the peri-ischemia cortex of the three groups were also evaluated at the same day by western blot.Results1.Effects of CIMT on neurological severity after cerebral ischemia-reperfusion in ratsThe neurological functions of both groups were improved in varying degrees with prolongation of ischemic and fixed time.Compared with I/R group,the motor function, balancing function and mnemonic function of CIMT group were all improved in the 14^thand 21^stdays after cerebral ischemia-reperfusion.There was not statistically significant between the two groups in the 28^thand 35^thdays. 2.Effects CIMT on the expression of Rho kinase after cerebral ischemia- reperfusion in ratsThe expression of Rho kinase in CIMT group in 21^thday after cerebral ischemia-reperfusion turned to minimal level,and it then returned to normal level gradually in 35^thday after cerebral ischemia-reperfusion.The expression of Rho kinase in I/R group also decreased in 14^thday after cerebral ischemia-reperfusion,the expression of Rho kinase in CIMT group decreased more obviously than the I/R group in 14^thand 21^stdays after cerebral ischemia- reperfusion.Conclusions1.CIMT can improve the motor function,balance ability and the faculty of memory significantly.2.CIMT can decrease the expression of Rho after cerebral ischemia-reperfusion in rats,and the decrease is more obvious after 2 weeks with constraint-induced movement therapy.It will then return to normal level gradually with time-lapse.