The effects of neural stem cell transplantation on Foxg1 gene expression in the subgranular zone of neonatal brain tissue damaged by hypoxia-ischemia / 中华物理医学与康复杂志

ABSTRACT

Objective To observe the effect on Foxg1 gene expression in the subgranular zone (SGZ) of cerebral tissue from neonatal rats with hypoxic-ischemic brain damage (HIBD) after transplantation of neural stem cells (NSCs) derived from umbilical cord blood.Methods Mononuclear cells separated from umbilical cord blood by density gradient centrifugation were cultured with orientated induction to differentiate the NSCs.The neuronal phenotype was identified using immunocytochemical methods.A total of 150 Sprague-Dawley rats were randomly divided into a sham-operation group,an HIBD group and an HIBD-NSCs group.Rats in the HIBD group and the HIBD-NSCs group were subject to ligation of the left carotid artery and then kept in a box under 8％ oxygen and 92％ nitrogen for 2.5 hours to establish the HIBD animal model.The artery was separated but not ligated in the sham operation group,which was not subjected to hypoxia.Twenty-four hours after the operation,the cultivated NSCs were transplanted by caudal vein injection into the rats in the HIBD-NSCs group.Rats were then sacrificed on the 3rd,7th,14th,21st and 28th days after the operation.Foxg1 gene expression in the SGZ was examined using in-situ hybridization methods.Results The number of Nestin-positive cells peaked on the 6th day of cultivation and then decreased by the 9th day.The Foxg1 gene was expressed in the SGZs of each group.The expression increased by the 3rd day after surgery in the HIBD and HIBD-NSCs groups,and peaked on 7th day after the operation,then declined gradually.The average expression level of Foxg1 in the HIBD group was significantly lower than that in the HIBD-NSCs group on the 7th day and thereafter.Conclusions Human umbilical cord blood mesenchymal stem cells can be induced and differentiated into neural stem cells.Foxg1 genes can still be present in the SGZ after birth.HIBD can induce the expression of Foxg1 genes.Transplanting NSCs can promote the expression of Foxg1 genes and improve morphological and functional recovery after HIBD,at least in neonatal rats.