The Effects Of GDNF Gene Modified Neural Stem Cells Transplantation To The Expression Of Neural Stem Cells And Astrocytes In Rats Subjected To Cerebral Ischemia Reperfusion

Abstract:Objective:To investigate the glial derived neurotrophic factor (glial cell line-derived neural factor, GDNF) gene modified neural stem cells (neural stem cells, NSCs) transplantation in rats with cerebral ischemia of neural stem cells and astrocytes effects. Methods:A rat model of transient middle cerebral artery occlusion (middle cerebral artery occlusion, MCAO), and randomly divided into:saline transplantation group (NS), neural stem cell transplantation group (NSCs) and the GDNF gene modified neural stem cell transplantation group (GDNF/NSCs). Then according to reperfusion time in each group were divided into five sub-groups (1W,2W,3W,5W,7W,6 rats at each time point).3d reperfusion brain stereotactic apparatus used to graft implantation in the right lateral ventricle of rats. Reperfusion at different time points (1W,2W,3W,5W,7W, including immunohistochemistry and Western blot all three rats) rats were killed, taking the ipsilateral hemisphere. By immunohistochemistry (immunohistochemistry, IHC) method, using nestin antibody proliferation of neural stem cells, using immunoblotting (Western blotting) methods, Observed with GFAP antibody reactions of astrocytes. Results:1, the experimental group, Nestin-positive cells were mainly distributed in the ischemic side frontoparietal cortex, striatum, hippocampus.2, Nestin-positive cells in statistical analysis showed that:GDNF/NSCs, NSCs group of Nestin positive cells in the lowest 1w,3w peak, then reduced gradually. NS Group Nestin-positive cells 1w highest, then decreased gradually. And reperfusion 1-7w, GDNF/NSCs group, NSCs group Nestin-positive cells was significantly higher than the NS group (P<0.05), whereas reperfusion 2w,3w, GDNF/NSCs group of Nestin-positive cells was significantly higher than the NSCs group (P<0.05).3, GDNF/NSCs group, NSCs group and NS group were GFAP protein 2w peak, then gradually decreased. And reperfusion 1-7w, GDNF/NSCs group of GFAP protein were significantly higher than the NS group (P<0.05); GDNF/NSCs group of GFAP expression was significantly higher than NSCs group (P<0.05). Reperfusion 1-5w, NSCs group GFAP expression was significantly higher than NS group (P<0.05). Conclusion:GDNF/NSCs transplantation rats with ischemia-reperfusion neuroprotective effect, the mechanism may be related to the promotion of neural stem cell proliferation and the number of the astrocytes. Our results for the stroke gene therapy and cell transplantation in clinical applications.