Therapeutic strategy against ischemic stroke with the concept of neurovascular unit.

Stroke is one of the leading causes of death and disability globally. Although thrombolytic therapy by t-PA and mechanical thrombectomy have improved outcomes of ischemic stroke patients, both of these approaches are applicable to limited numbers of patients owing to their time constraints. Therefore, development of other treatment approaches such as developing neuroprotective drugs and nerve regeneration therapy is required to overcome ischemic stroke. The concept of the neurovascular unit (NVU) was formalized by the Stroke Progress Review Group of the National Institute of Neurological Disorders and Stroke in 2001. This concept emphasizes the importance not just of neurons but of the interactions between neurons, endothelial cells, astroglia, microglia and associated tissue matrix proteins to investigate the pathological condition of ischemic stroke. Many reports have been published about these interactions. This review focuses on the roles of cells that surround cerebral vasculature, especially endothelial cells, and reports therapeutic strategies against ischemic stroke from four points of view including angiogenesis, neurotrophic effects, protection of NVU components and regenerative therapy.