The potential role of vascular endothelial growth factor in the central nervous system

During the past decade, vascular endothelial growth factor (VEGF) has been widely investigated, and reported to have pleiotropic functions in the central nervous system (CNS) and its supporting physiological environment. VEGF is involved in not only such well-known functions as angiogenesis, accentuation of vessel permeability, and glial proliferation, but also more recently acknowledged functions such as neuroprotection and even neurogenesis itself. Most recently, the neurogenesis function has attracted much attention, and a number of research groups have taken up the challenge of elucidating this activity. In keeping with this trend, our knowledge of VEGF receptors has increased, and certain suggestions concerning the mechanisms of neuroprotection have come to light in the course of the ongoing work, though at times what the researchers had to work with was only a tiny percent of the signal transduction of VEGF. Together with flt-1 (VEGF receptor 1) and flk-1 (VEGF receptor 2), neuropilin (NP) is frequently described as being involved in the neuroprotective effects of VEGF. In this review, both the direct and indirect neuroprotective effects of VEGF, including various signaling pathways as well as the neurogenesis induced by this factor, are discussed in the context of the newly emerging insights into the biological mechanisms of VEGF and closely related, interacting molecules.