The Co-expression Of VEGF And SDF-1Genes Promote Remodeling Of Neurovascular Unit After Cerebral Ischemia

Object:To investigate the function of combination of Vascular Endothelial Growth Factor (VEGF) and Stromal Cell-derived Factor-1(SDF-1) on remodeling of neurov-ascular unit, neurogenesis and neovascularization,in rats after cerebral ischemia.Methods:Transient middle cerebral artery occlusion(MCAO) model was induced on adult male rats by Longa’s method.60successful models were equally divided into2groups randomly, treatment group and control group, and received subventricle zone stereotaxis microinjection with Adv-VEGF-SDF-1or Adv-Lacz24h later. Rats were evaluated according to modified Neurological Severity Scores(mNSS) at3,7,14,21and28day after MACO. Immunofluorescence technique was utilized for the measureme-nt of VEGF and SDF-1expression in brain28d later. Double-labeled DCX and Brdu was used to evaluate proliferation of neural progenitor cells,and triple-labled DCX/VEGFR-2/CXCR4to detect neural precursor cells express VEGF and SDF-1recept-ors or not.CD34was labled to evaluate microvessel density; The volume of cerebral infarction was measured on the basis of T2WI of MRI by using IPP sofeware; Relative Cerebral Blood Flow(rCBF), relative Cerebral Blood Volume (rCBV) and relative Mean Transmit Time(rMTT) were calculated according to the ratio of infarcts and uninjured hemisphere.Results:(1)The mNSS scores of the treatment group was lower than the control group after the7th day(P<0.05) and the statistical differences increased with time;(2) VEGF and SDF-1molecule were detected in many different areas of brain,the positive cells in treatment group were significantly much more than control group;(3)The receptors of VEGF and SDF-1, VEGFR-2and CXCR4,were detected on neural precursor cells.(4) There were more double positive cells of DCX/Brdu in subventricular zone, rostral migratory stream and cortex in treatment group than in control group(P<0.05);(5) The microvessel density in treatment and control group were respectively380.25±83.43,209.25±49.24(P<0.05);(6)The relative volume of cerebral infarcts in treatment and control group were respectively23.65±1.71%、28.99±2.25%(P<0.05);(7)The number of rCBF. rCBV and rMTT in treatment and control group were respectively65.74±9.15%,114.17±17.27%,153.33±31.49%and47.17±8.22%,83.33±13.87%,222.00±52.72%(P<0.01).Conclusion:(1) The expression of VEGF、SDF-1in rats brain can be increased through adenovirus transfection;(2) Co-expression of VEGF and SDF-1can promote neovascularization and neurogenesis, induce more neural progenitor cells migrate to ischemic penumbra from SVZ,reduce volume infarcts,and improve cerebral perfusion, and the remodeling of neurovascular unit contributes to improved neurological function.