Transplantation Of GDNF Gene Modified Neural Stem Cells In Rats After Stroke Increase P44/42MAPK And AKT Cell Signaling Expression

Objective To study the effect of GDNF gene modified neural stem cells(GDNF/NSCs) transplantation to the rats subjected to cerebral ischemia reperfusion.Investigating whether the neuroprotective function connect with the activation of p44/42MAPK,its special inhibitor MKP-1,AKT or not.Methods:Temporary middle cerebral artery occlusion (MCAO) models were established,three days after MCAO,transplanting GDNF/NSCs,NSCs and NS.Then Rats of each group were divided into 5 subset according to reperfusion time(1,2,3,5,7 week).seven rats each time point:four were used to do TUNEL which could check the numbers of apoptosis neurocytes;three were used to do Western blotting which can check the defferent Phosphorylation of MAPK,AKT(pMAPK/MAPK,pAKT/AKT) and MKP-1. Results:1.The numbers of apoptosis neurocytes in all three groups were gradually decreased in the time points of 1w,2w,3w,5w,7w.The numbers of apoptosis neurocytes in GDNF/NSCs and NSCs group were significantly lower than NS group(P=0.000 P=0.01);The numbers of apoptosis neurocytes in GDNF/NSCs group were significantly lower than NSCs group(P=0.005).2.The proportionality of pMAPK/MAPK in all three groups was gradually decreased in the time points of 1w,2w,3w,5w,7w. The proportionality of pMAPK/MAPK in GDNF/NSCs and NSCs group was significantly higher than NS group (P=0.000 P=0.000).The proportionality of pMAPK/MAPK was significantly higher than NSCs group(P=0.000).3.The expression of MKP-1 in all three groups reached the top in 2w;the expression of MKP-1 in NS group and NSCs group was higher than GDNF/NSCs group(P=0.000 P=0.001);the expression of MKP-1 in NS group was higher than NSCs group (P=0.005).4.The proportionality of pAKT/AKT in all three groups was gradually decreased in the time points of 1w,2w,3w,5w,7w. The proportionality of pAKT/AKT in GDNF/NSCs group was significantly higher than NS group and NSCs group(P<0.001).In NSCs group, the proportionality of pAKT/AKT was significantly higher than NS group in 1w,2w,3w (P＜0.001).In 5w the proportionality had no statistical meaning (P=0.10).The proportionality was also significantly higher than NS group in 7w(P=0.05).Conclusion:The treatment of GDNF/NSCs transplantation to brain inury of ischemia reperfusion had obvious effects.The mechanism might be connected with the phosphorylation activation of MAPK andPI3K/AKT.