Brain angiogenesis in developmental and pathological processes: therapeutic aspects of vascular endothelial growth...

The angiogenic process in the central nervous system (CNS) is basically regulated by typical angiogenic signaling systems such as vascular endothelial growth factor (VEGF)-VEGF receptors and angiopoietin-Tie receptors. In addition to regular endothelial-pericyte interaction, the CNS vasculature has a unique system of cell to cell communication between endothelial cells and astrocytes which is known as the blood-brain barrier. Among the pathological conditions of the CNS vascular network, stroke is a major disease in which the supply of blood is decreased. Pro-angiogenic therapy using natural VEGF-A has so far been unsuccessful, indicating the possible need for a new approach related to upstream or downstream regulators involved in the VEGF-signaling pathway, or alternate VEGF family members. By contrast, a pathological increase in the blood supply in the CNS is seen in brain tumors, in particular malignant gliomas. In phase II clinical trials, anti-VEGF therapies have been shown to suppress tumor growth and improve survival rates to some extent. However, tumor invasion and the distant metastasis of gliomas can occur following anti-angiogenic therapy. Further studies are needed to obtain safer clinical outcomes by developing new strategies with combination therapy using known anti-angiogenic drugs or by developing unique medicines specifically targeting the blood vessels in brain tumors.