Effects Of Constraint-Induced Movement Therapy On Neurotrophic Factors In MCAO Rats

ObjectiveThe study was to observe the effect of Constraint-induced movement therapy(CIMT)on the overall motor performance and on infarction area in cerebral ischemic rats.With the aim of exploring the possible mechanism of CIMT and providing experimental basis for its clinical promotion in the future,the study examined CIMT’s adjustment to Brain-derived neurotrophic factor(BDNF)and Nerve growth factor(NGF).MethodsHealthy male Sqrague-Dawley(SD)rats were selected and randomly divided into 3 groups:Sham group(n=9),MCAO group(n=12)and CIMT group(n=15).The middle cerebral occlusion was performed to the rats from MCAO group and CIMT group,while the Sham group rats only have their vessels separated.The CIMT model was established after 7 days of the surgery.The training began on day 8th,consisting of retarod training,balance beam training and screen training.A ten-minute-training was conducted twice a day for two weeks.Before the surgery,all the rats were familiarized with all the evaluation devices.The three groups’ score of Retarod test was recorded three days before the surgery.The weigh was taken down on the day before the surgery,day 1st,day 14th and day 21st.Neurological severity and behavioral assessment were delivered on day 1st,day 14th and day 21st.All the rats were executed on day 21st and parameters on the ischemic side(left side)were measured by immunofluorescence:the expression of NeuN,the area of cerebral infarction,the expression of BDNF and NGF in corpus putamen(CPu)and four regions of hippocampal(dentate gyrus,CA3,CA2,CA1).Results1.According to the Longa score,the model was successfully established(P<0.01).The rats from CIMT group and MCAO group suffered similar damage without significant difference(P>0.05).2.After the training,all the rats had their weight increased.Meanwhile those from CIMT group increased slower than other two groups(P<0.01).3.CIMT group’s performance,which is approximate to the level of the Sham group in Screen test(P>0.05),was better than MCAO group’s in neurological severity test and behavior test after the training.4.The cerebral infarction area of CIMT group was visibly smaller than MCAO group.There were significant differences among the three groups(P<0.01).5.The BDNF expression of the CIMT group in the ischemic CPu was much higher than other two groups(P<0.05),so was the NGF expression.6.As for the BDNF expression in the four regions of hippocampal,CIMT group was much higher than the other two groups while MCAO group was lower than Sham group.Observing from each region,the CPu’s BDNF expression of CIMT group was obviously higher than MCAO group(P<0.01)and Sham group.The CPu’s NGF expression of CIMT group was the highest(P<0.05).The BDNF expression in CA3 was evidently higher than the others(P<0.01).The NGF expression in CA2 was higher than MCAO group(P<0.05).7.Compared by groups,the BDNF expression of CIMT and Sham group were the highest in DG,following by CA3,CA1 and CA2.The ranking of two groups’NGF expression was DG,CA1.CA3 and CA2.The MCAO’s BDNF expression was the highest in CA3,following by CA1,DG and CA2.The CA1 was the highest MCAO’s NGF expression area,then DG and CA3,CA2.ConclusionsCIMT could effectively improve neurological function and extremity motor function of MCAO rats.CIMT also helped reducing cerebral infarction area as well as increasing the BDNF and NGF expression of CPu and hippocampal on the ischemic side,which contributed to cerebral injury repairing and neuroprotection.