Vascular endothelial growth factor (VEGF) promotes neurogenesis in the subventricular zone (SVZ),hippocampal dentate gyrus (DG),and the striatum of adult mammalian brains.However,effect of VEGF on cortical neurogenesis after stroke remains unclear.Here,we intraventricularly injected human VEGF.165-expressive plasmids (phVEGF) into rat brains after a transient middle cerebral artery occlusion (MCAO) and examined effects of VEGF on stroke-stimulated cortical neurogenesis.The results showed that 5-bromodeoxyuridine positive (BrdU+,a DNA-replication marker) cells were found in ipsilateral frontal cortex at 2 weeks of reperfusion and declined over time.Injection of phVEGF did not alter such a decline,but it significantly increased BrdU+ cells compared with the control plasmid (pEGFP) injection at 2,4 and 8 weeks after MCAO.Ischemia-induced cortical neurogenesis was indicated by the presence of newborn immature (BrdU+-Tuj1+),newborn mature (BrdU+-MAP-2+),and newborn GABAergic (BrdU+-GAD67+) neurons.M1 these neurons declined within 8 weeks after MCAO in the controls.Injection of phVEGF significantly increased BrdU+-Tuj 1+ neurons at 2 weeks,and BrdU+-MAP-2+ neurons and BrdU+-GAD67+ neurons at 4 and 8 weeks after ischemia.Neurite length and branch numbers of BrdU+-MAP-2+ newborn neurons in the cortex were detected in both groups.Injection of phVEGF significantly increased neurite length and branch numbers of BrdU+-MAP-2+ newborn neurons.These results demonstrate that VEGF enhances ischemia-induced cortical neurogenesis and maturation of newborn neurons.Present study further indicates that neuroprotection of VEGF against ischemic injury may associated with enhancement of neurogenesis in adult mammalian brains.