HIF-1, an important regulator in potential new therapeutic approaches to ischemic stroke

Ischemic stroke is a leading cause of disability and mortality worldwide due to the narrow therapeutic window of the only approved therapies like intravenous thrombolysis and thrombectomy. Hypoxia inducible factor-1 alpha (HIF1 alpha) is a sensitive regulator of oxygen homeostasis, and its expression is rapidly induced after hypoxia/ischemia. It plays an extensive role in the pathophysiology of stroke by regulating multiple pathways including glucose metabolism, angiogenesis, neuronal survival, neuroinflammation and blood brain barrier regulation. Here, we give a brief overview of the HIF-1 alpha-targeting strategies currently under investigation and summarise recent research on how HIF-1 alpha is regulated in various brain cells, including neurons and microglia, at various stages in ischemic stroke. The roles of HIF-1 in stroke varies with ischemic time and degree of ischemia, are still up for debate. More focus has been placed on prospective HIF-1 alpha targeting drugs, such as HIF-1 alpha activator, HIF-1 alpha stabilizers, and natural compounds. In this review, we have highlighted the regulation of HIF-1 alpha in the novel therapeutic approaches for treatment of stroke.