Implications of Vascular Endothelial Growth Factor for Postischemic Neurovascular Remodeling

Neurovascular remodeling has been recently recognized as a promising target for neurologic therapies. Hopes have emerged that, by stimulating vessel growth, it may be possible to stabilize brain perfusion, and at the same time promote neuronal survival, brain plasticity, and neurologic recovery. In this review, we outline the role of vascular endothelial growth factor (VEGF) in the ischemic brain, analyzing how this growth factor contributes to brain remodeling. Studies with therapeutic VEGF administration resulted in quite variable results depending on the route and time point of delivery. Local VEGF administration consistently enhanced neurologic recovery, whereas acute intravenous delivery exacerbated brain infarcts due to enhanced brain edema. Future studies should answer the following questions: (1) whether increased vessel density translates into improvements in blood flow in the hemodynamically compromised brain; (2) how VEGF influences brain plasticity and contributes to motor and nonmotor recovery; (3) what are the actions of VEGF not only in young animals with preserved vasculature, on which previous studies have been conducted, but also in aged animals and in animals with preexisting atherosclerosis; and (4) whether the effects of VEGF can be mimicked by pharmacological compounds or by cell-based therapies. Only on the basis of such information can more definite conclusions be made with regard to whether the translation of therapeutic angiogenesis into clinics is promising.