Constraint-induced Movement Therapy Improves The Cognitive Function In Rats After Cerebral Ischemia By Increasing The Level Of SIRT1 In The Hippocampus

Objective: To investigate the effect of constraint-induced movement therapy(CIMT)on cognitive function in rats with cerebral ischemia,and the effect of CIMT on the expressions of silencing information regulator 1(SIRT1)and brain-derived neurotrophic factor(BDNF)in the dentate gyrus(DG),CA1,and CA3 regions of hippocampus,and the possible mechanism underlying these effects.Methods: Adult male Wistar rats were randomly divided into three groups:sham-operated rats(SHAM group),cerebral ischemic rats(ISC group)and ischemic rats treated with CIMT(ISC+CIMT group).The focal cerebral ischemia was initiated by injecting endothelin(ET-1)into in the motor cortex and striatum of brains.The SHAM group was injected with the same amount of normal saline at the same site.CIMT was induced by using plaster cast around the unimpaired upper limbs and trunk in rats one week after focal cerebral ischemia to force the rats to use the affected limb,and was lasted for 3 weeks.We used Morris water maze to assess the congnitive function of rats after ischemia and the effect of CIMT on the congnitive function of ischemic rats.The Morris water maze was carried out from day 30 to day 32 after ischemia onset and lasted for 3 days.After the behavioral test,the rats were sacrificed for brain fixation,dehydration,and implantation 33 days after the operation of cerebral ischemia,and the frozen brain sections were prepared.The expressions of SIRT1 and BDNF in the DG,CA1,and CA3 regions of hippocampus were evaluated by immunofluorescence staining and confocal microscopy.Results: There was a significant difference in the escape latency between the groups(F(2,21)=11.80,P<0.01).The result of the spatial navigation trial showed that the escape latency of ISC group rats was significantly higher than that of SHAM group(P<0.01),while the escape latency in ISC+CIMT group rats was significantly lower than that of ISC group(P<0.05).The results of the probe trial domenstrated that the number of passes over the target platform within 60 seconds in ISC group was significantly lower than that of SHAM group(P<0.01),and the number of passes in ISC+CIMT group was significantly increased compared with that of ISC group (P<0.01).The results of immunofluorescence staining suggested that CIMT treatment significantly increased the expression of SIRT1 in the DG(P<0.01)and CA1 region(P<0.05)of the hippocampus after cerebral ischemia in rats.There was no significant difference between the groups in the expression of SIRT1 in CA3 region and the expression of BDNF in the different regions of hippocampus(P>0.05).Conclusion: CIMT significantly promoted the recovery of cognitive functional recovery in rats after cerebral ischemia,which might through increasing the expression of SIRT1 in the hippocampus but not through the SIRT1-BDNF pathway.