心肌营养素1修饰的神经干细胞移植对癫(癎)持续状态大鼠海马损伤及苔藓纤维发芽的影响

Objective To observe the survival,migration and differentiation of grafted neural stem cells(NSCs)transfected with cardiotrophin-1(CT1)in hippocampus in status epilepticus(SE)rats,and investigate its effect on neuron loss and mossy fiber sprouting(MFS)in hippocampus of SE rats.Methods (1)Lithium-pilocarpine induced SE model rats were divided into 3 groups randomly:CT1-NSCs transplantation group(n=18);NScs transplantation group(n=18)and SE model group(n=18).Another 18 rats served as normal control group.Each group was further divided into 3 time points testing groups(n=6 at each point)corresponding to 1,4 and 8 weeks after transplantation respectively.(2)Under the confocal microscopy,the survival,migration and differentiation of the grafted cells were observed by immunofluorescenee.(3)Morphological changes and neuron loss in the hippocampal CA1 region were examined by Nissl staining.(4)MFS in hippocampal dentate gyrus in rats was obserred by Timm histochemistry.Results(1)At 4 and 8 weeks post-tmusplantation,the numbers of double-labeled NF-200 and EGFP pesitive cells in the CT1-NSCs group were significantly hisher than those in NSCs group.In the former group most of the grafted NSCs migrated away from the needle tract,but in the latter group,grafted ceHs remained at the transplantation site.(2)The numbers of neuron in the hippocampal CA1 region reduced gradually after SE.The numbers of neuron in the CA1 region in CT1-NSCs transplantation rats (68.85±11.49,60.89±12.17 and 51.51±13.34 in 1,4,8 weeks after transplantation respectivelv)were greater than that in NSCs transplantation rats(67.92±10.78,42.56±11.47 and 30.49±10.12).tvalue were 4.650 and 5.334 in 4 and 8 weeks after transplantation(P<0.05).(3)Aberrant MFS in the inner molecular layer of dentate gyrus was observed,and the scores of MFS gradually increased with timelapse.The scores of MFS in CT1-NSCs transplantation rats(0.77±0.04,2.48±0.89 and 2.39±0.82 in 1,4,8 weeks after transplantation respectively)were significant lower than that in NSCs transplantation rats (1.12±0.62,3.17±0.64 and 3.88±0.51,t=6.059,9.511 and 9.728,P<0.05).Conclusions CT1 could promote the survival,migration and differentiation of engrafted NSCs in hippocampud in SE rats.Engrafted NSCs transfected with CT1 have effect on repair of the injured hippocampus,and could inhibit hippocampus MFS in SE rats.

Effects of transplanting neural stem cells transfected with cardiotrophin-1 on the injured hippocampus and mossy fiber sprouting in status epilepticus rats