Researches On Effects And Its Mechanisms Of Willed Movement On Neurological Performance In Rats Following Focal Cerebral Ischemia

Objective:To explore the effects and its possible mechanisms of willed movement on neurological performance in rats following focal cerebral ischemia.Methods:A total of144male Sprague-Dawley rats were randomly divided into four groups:middle cerebral artery occlusion (MCAO), swimming exercise (SE), environment modification (EM), and willed movement (WM)., each of which further divided into three subgroups according to7,15,30days after reperfusion. Reversible middle cerebral artery occlusion model was established by intraluminal suture. Neurological and neurobehavioral assessments were performed At1,3,7,15and30day after reperfusion to evaluate the neurological deficiency. Infarction volume was detected by TTC staining at15day after reperfusion. Reverse Transcription PCR(RT-PCR) was used to detect the extrcellular signal regulated kinase (ERK)/cAMP response element binding protein (CREB) and GluR2mRNA. Simultaneously, the phosphorylated ERK (pERK)/phosphorylated CREB (pCREB) protein and co-expression of GluR2and protein interacting with Ca kinase (PICK1) in the ischemic penumbra were detected by single-labeled and double-labeled immunofluorescence respectively. Results:①Neurological and neurobehavioral assessments showed the climbing frequency of WM was significantly higher than EM (P<0.05). Compared with MCAO, the neurologic deficit scores of WM and EM decreased (P＜0.05), of which WM decreased more apparently (P<0.05)②TTC staining showed that compared with MCAO, the infarction volume of EM and WM were reduced at the15day after reperfusion (P<0.05), while there was no significant differences between SE and MCAO (P>0.05)③RT-PCR showed that the ERK、CREB and GluR2mRNA in the ischemic penumbra were markedly up-regulated in WM and EM at7,15and30day after reperfusion compared with MCAO (P<0.05), of which the difference of WM was the most apparent (P＜0.05). There was a slightly down-regulation of the ERK/CREB mRNA of SE at7th day from reperfusion (P<0.05), and then following with significantly up-regulation at15,30day after reperfusion (P<0.05), while the GluR2mRNA showed continuous up-regulation in SE (P＜0.05).④Immunofluorescence showed an up-regulation of pERK/pCREB protein expression in WM and EM at7,15,30day after reperfusion(P＜0.05)compared with MCAO. Similar to the expression of ERK/CREB mRNA, pERK/pCREB protein in SE decreased slightly at7day after reperfusion (P＜0.05), while increased at15,30day after reperfusion compared with MCAO.(P＜0.05). At 15day after reperfusion, GluR2and PICK1positive cells in SE,EM and WM increased significantly when comparing with MCAO(P<0.05), and there was highly consistency of the distribution between GluR2and PICK1proteins. The proportion of double-positive cells of GluR2and PICK1protein was significantly higher in WM than those in the other three groups (P<0.05).Conclusions:Willed movement may promote motor recovery in rats following focal cerebral ischemia by up-regulating ERK/CREB and enhancing interaction between GluR2and PICK1.