Migration and differentiation of transplanting neural stem cells modified by cardiotrophin-1 in hippocampus and its effect on the spatial memory in status epilepticus rats

Abstract

Objective To observe the survival,migration and differeraiation of grafted neural stem cells (NSCs) modified by cardiotrophin-1 (CT1)in hippocampus in status epilepticus (SE) rat,and its effect on the soatial memory in SE rats.Methods (1)NSCs were cultivated and transfected with adenovirus CT1,marked withenhance green fluorescent protein (EGFP) in vitro (2)54 Pilocarpine-SE model rals were divided into three groups randomly:CT1-NSCa-EGFP transplantation group(n=18);NSCs-EGFP trangplantation group (n=18);model control group(n=18).Another 18 rats served as normal control group,Each group was divided into three time points equally(each point,n=6)corresponding to 1 week,4 weeks and 8 weeks after transplantation.(3) Under the confocal microscopy,the survival,migration and differentiation of the grafted cells were observed by immunofluorescent stainirlg for EGFP(green),NF-200(red),and double-labeled(yellow).The spatial memory of the SE rate was tested by Morris wafer maze task. Results At 4 weeks and 8 weeks after transplanlation,the numbers of EGFP-positive and double-labeled cells in the CT1-NSCs-EGFP transplantation group were more significantly increased than those in the NSCs-EGFP transplantation group.In the CT1-NScs-EGFP transplantation group.mosl of the grafted NSCs migrated away from the needle tract.But in tlle NScs-EGFP transplantation group.the majority of grafted cells remained at the transplantation site.The latency period of escape markedly decreased at 4 and 8 weeks in the rats transplanted by CT1-NSCs-EGFP compared with those by NSCs-EGFP(P<0.05).Conclusions CT1 could promote the survival,migration and differentiation of engrafted NSCs.Engrafted NSCs combined with CT1 could improve the spatial memory in SE rats. Key words: Cardiotrophin-1; Neural stem cells; Transplantation; Status epilepticus