Protective Role Of Neural Stem Cells In Ischemic Stroke

Background and objectives Stroke is a major cause of neurological disability,stem cell replacement therapy is attractive as a novel strategy for stroke patients.This study is aimed to examine the role of NSCs administration in rats after ischemic stroke.Glycogen synthase kinase-3(GSK-3)is one of the few signaling molecules that regulate a truly astonishing number of critical intracellular signaling pathways.TWS119 is a GSK-3? inhibitor with IC50 of 30 n M.This study investigated the effects of GSK-3? inhibitor in protecting neurons against oxygen-glucose deprivation injury.Methods Cell viability assay was performed using MTT.Neurite lengths quantifications were processed by image J in neurons with MCP-2 staining.The protein expression levels of Bax,Bcl2 and Mcl-1 were analyzed by western blot.Inflammatory cytokines were investigated by multiplexed sandwich ELISA-based quantitative array.Primary cultured embryonic neural stem cells(NSCs)and brain microvascular endothelial cells(BMECs)were in-directly co-cultured to process in vitro test.Rat model of embolic middle cerebral artery occlusion(MCAO)was conducted to test morphology and functional change after treatment with NSCs.Results OGD-induced neurotoxicity was significantly inhibited in neurons pre-treatment with different concentrations of GSK-3? inhibitor(5-20?M).GSK-3? inhibitor also attenuated the OGD-induced Bcl-2/Bax ratio reduction in neurons.There was a significant reduction in inflammatory cytokines and pro-apoptotic protein for 12 h OGD-treated neurons.We presented experimental evidence supporting the notion that administration of NSCs may reduce the brain injury of stroke in vivo and in vitro.Furthermore,our data suggests that activation of PI3k/AKT/GSK-3? pathway and attenuation of inflammatory reaction,autophagy may contribute to the underlying beneficial effect of NSCs.Accumulating evidence has suggested that NSCs promote endogenousneurogenesis to improve functional recovery after stroke in rats.Conclusion Our findings suggest that GSK-3? inhibitor plays a critical neuro-protective role in OGD treated cell through its anti-inflammatory and anti-apoptosis effects,and this indicates that GSK-3? inhibitor may be a promising novel therapeutic target in ischemic stroke.Multiple processes engaged in neural protection role of NSCs.