Hypoxia-Inducible factor-1α promotes neuroregeneration and angiogenesis after cerebral ischemia

To promote neuroregeneration and angiogenesis is a therapeutic target for the treatment of stroke. Hypoxia-inducible factor-1α (HIF-1α) has pleiotropic effects on neurogenesis, angiogenesis and neuroprotection in central nervous system. In this study we investigated whether HIF-1α treatment promotes the proliferation of ischemia induced neural stem cells (NSCs) and neuroregeneration in penumbra. The angiogenesis in penumbra was also investigated. Transient middle cerebral artery occlusion (tMCAO) rat model was used in this study. Rats were divided into 3 groups, Sham group, vehicle group and HIF-lα group. In this study, we found that rats with HIF-1α treatment had better behavioral recovery at day7, 14, 21 and 28 (p<0.05). HIF-lα treatment increased the number of ischemia induced endogenetic NSCs in penumbra obviously (p<0.01). HIF-1α also improved newborn neurons and glial cells in penumbra on the 28 d (p<0.01). HIF-1α treatment promoted expression of erythropoietin (EPO) in peri-ischemic area. Vascular endothelial growth factor (VEGF) expression in HIF-lα group was significantly higher than that in vehicle group (p<0.01). Number of CD 31 positive vascular in penumbra in HIF-lα treatment group was much more than that in vehicle group (p<0.01). In conclusion, our results indicate that modulate HIF-1α after ischemia may be a therapeutic target for the treatment of ischemic stroke through promoting neuroregeneration and angiogenesis.