Overexpression Of SDF-1 Gene Promotes NPCs Synapse Formation After Stroke

Objective:To explore the role of overexpression of stromal cell-derived factor-1(SDF-1)gene in synaptogenesis of NPCs after stroke.Methods:The middle cerebral artery ischemia-reperfusion(MCAO)model was established in adult male SD rats by modified Longa's thread embolization method.The model was randomly divided into experimental group and control group.One day later,rAAV1-SDF-1and rAAV1-LacZ were injected into the affected ventricles of the two groups by stereotactic microinjection.The dynamic neurobehavioral scores of the two groups were evaluated at 3,7,14,21 and 28 days after operation.After 6 weeks,the brain tissues of the experimental group and the control group were taken and the expression of SDF-1 and its receptor CXCR4 was measured by Weston blot and ELISA,the mRNA levels of sdf-1 and CXCR4 were quantitatively detected by qPCR.The expression of SDF-1 gene in endothelial cells,glial cells,neurons and nerve precursor cells was detected by immunofluorescence multiple labeling technique.The synaptic formation of NPCs in the ischemic penumbra of the experimental group and the control group was detected by double-label SYP/DCX.The relationship between synaptic formation and microcirculation was observed by double-label SYP/CD31.Results:(1)In the first week after MCAO model,there was no significant difference in mNSS scores between the experimental group and the control group,but one week later,the score of the experimental group began to be lower than that of the control group,and with time passing,the difference of mNSS between the experimental group and the control group was more obvious;(2)SDF-1 and CXCR4 genes and protein expression in the brain of the experimental group rats increased significantly compared with the control group(P < 0.05);(3)Immunofluorescence multiple labeling showed that SDF-1 expression in striatum was significantly increased in endothelial cells,glial cells,neuronal precursor cells and neurons in experimental group compared with control group;(4)The number of synapses in striatum,subventricular area and ischemic penumbra of experimental group was significantly increased compared with control group(P < 0.05);(5)Compared with the control group,the blood vessels in the penumbra of ischemia in the experimental group were complete,continuous and synaptic intensive,and mainly concentrated around the blood vessels.Conclrsions:(1)SDF-1 gene therapy can promote the recovery of neurological function in rats after stroke.(2)SDF-1 can promote the formation of NPCs synapses after stroke.(3)The synaptic formation of NPCs after stroke is closely related to microcirculation.