| Background and objectiveSome study showed that Rats following WM intervention showed significantly better acquisition of climbing (every time point tested), forelimb mobility and neurological functions at subacute stage of MCAO. Early willed movement treatment can increase the expression level of AMPA receptor subunits especially the number and intensity of GluR2in IP (ischemicpenumbra) region and thus might increase synaptic transmission and enhance brain plasticity after focal brain ischemia at the subacute stage. But the mechanisms of GluR2expression regulation are not clear. GRASP-1was previously identified as a direct binding partner of glutamate receptor interacting protein1(GRIP1) and thought to be a guanine nucleotide exchange factor (GEF) for h-Ras.GRASP-1is a protein specially expressed in neurons but not in other cell types in brain or in other tissues. In the brain, GRASP-1specifically forms a complex with GRIP1and GluR2.GRASP-1may regulate AMPA receptor distribution, cycle, as well as synaptic plasticity. Adult rat models of cerebral ischemia-reperfusion injury were established by middle cerebral artery occlusion (MCAO) for2h followed by24h reperfusion. Using the climbing frequency, neurological behavior evaluation, forelimb and hind limb test to know the change of Behavioral recovery, TTC staining to measure the infarct volume, immunohistochemistry to detect the chang of GluR-2and GRASP-1, reveal the possible mechanism of willed movement.MethodsThe healthy male SD rats weighting200～300g was induced by middle cerebral artery occlusion (MCAO).After the MCAO, the rats were randomly divided in to TTC group and immunohistochemistry. Each group also have four different groups:MCAO group; CR (control rehabilitation) group; EM (environment modification) group; WM(willed movement) group.The adult male SD rats were killed at3,7,15,30day recirculation times after120-min period of occlusion of the right middle cerebral. The neurological behavior evaluation were performed at1,3,7,15,30day recirculation times MACO for each groups. The climbing frequency, forelimb and hind limb test were performed at3,7,15,30day recirculation times MACO for group of WM, CR and EM. Immunohistochemistry were used to detect the GluR2and GRASP-1in the areas of IP. Results(1) In the climbing frequency test, the numbers of climbing in WM group rats were significantly higher than those in EM, CR group rats after MCAO at either time point tested after MCAO especially at7day,15day and30day. Furthermore, rats in WM group have improved more than rats in EM and CR group in forelimb test at15-30day reciculation post-infarction and Neurologic Deficit Score test at30day recirculation post-infarction. The hind limb performance did not differ between two groups at either time point tested after MCAO.(2)TTC staining showed the infarct volume were increased in group WM at15day and30day recirculation post-infarction.(3)Immunohistochemistry results showed that GluR2protein expression were significantly higher than in group WM at30day recirculation post-infarction.(4) The correlation analysis showed in rats GluR2and GRASP-1protein expression was significantly correlated after recirculation post-infarction. Conclusion:Early willed movement movement might induce the increase of GRASP-1in rats suffered ischemia-reperfusion injury to raise the expression of GluR2, and then raise synaptic transmission and enhance brain plasticity after brain ischemia in the subacute stage. |
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