Effect Of Citicoline In Combination With Rehabilitative Training On Neuroethology And Neural Plasticity After Focal Cerebral Ischemia In Rats

ObjectivesTo observe the effect of citicoline in combination with rehabilitative training on motor function and the expression of S-100,β-tubulin after focal cerebral ischemia in rats, It also provides academic foundation for medicine in combination with rehabilitative training.MethodsOne-hundred and twenty male adult Sprague-Dawley rats(3 month old, n=100) were subjected to left middle cerebral artery occlusion (MCAO) with the suture occlusion and ninety-six rats consistent with the standard were randomly divided into four group:control group(n=24), citicoline group(n=24), rehabilitative training group(n=24), citicoline in combination with rehabilitative training group(n=24). Three day after reperfusion, the rats in citicoline group were received citicoline on dose of 500mg/Kg daily, those in rehabilitative training group were received motor training programs including balancing, grasping, rotating and walking exercise, those in citicoline in combination with rehabilitative training group were received citicoline and motor training programs, those in control group were not recevived any treatment. The behavioral tests of every group were evaluated at the 7th,14th,21st day after MCAO. And Immunohistochemistry staining method was used to detect the expression of S-100 andβ-tubulin of peri-ischemia cortex at the 7th,14th,21st day after MCAO respectively.With SPSS 13.0 statistical software, and the differences among the groups were compared with the One-Way ANOVA and Newman-Keuls test. A value of P<0.05 was considered statistically significant.Results1.The rat of every group appear the sign of nervous function defect after MCAO successful.2. neuroethology assessmentAs compared with the control group, citicoline group at the 7th,14th,21st day after MCAO and rehabilitative training group, citicoline in combination with rehabilitative training group at the 7th day after MCAO were no significant difference (P>0.05), but rehabilitative training group, citicoline in combination with rehabilitative training group at the 14th,21st day after MCAO(P<0.05) significantly superior to the control group, especially in the citicoline in combination with rehabilitative training group (P<0.01).3. Immunohistochemistry Staining MethodAs compared with the control group, the expression of S-100 andβ-tubulin of citicoline group, rehabilitative training group at the 7th day after MCAO were no significant difference respectively(P>0.05), but the citicoline in combination with rehabilitative training group was significant higher than other group at the 7th day after MCAO(P<0.05); As compared with the control group, the other group respectively was significant higher at the 14th,21st day after MCAO(P<0.05), especially in the citicoline in combination with rehabilitative training group (P<0.01).Conclusions1.Citicoline in combination with reasonable and obviously rehabilitative training can significant improve motor functional recovery in rats.2.Citicoline and rehabilitative training can promote the recover of nervous injury after focal cerebral ischemia in rats, the effect of combined modality therapy was more obvious.3.the functional recovery may be partially attributed to the up-regulation of S-100 andβ-tubulin in peri-ischemia cortex.