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

Abstract

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 can increase the proliferation of ischemia induced neural stem cells in SVZ 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, NS group, vehicle group and HIF-lα group.  In 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 SVZ obviously (p<0.01). HIF-1α also increased newborn neurons and glial cells in penumbra on the 28 d (p<0.01). Angiogenesis in penumbra was promoted by HIF-lα treatment(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 increasing neuroregeneration and angiogenesis.