Vascular endothelial growth factor and its high-affinity receptor (VEGFR-2) are highly expressed in the human forebrain and cerebellum during development.

Vascular endothelial growth factor (VEGF) is an angiogenic and neurotrophic factor in both adult and neonatal animals, but its expression and role have been incompletely studied in the developing human brain. We analyzed the distribution of VEGF and its high-affinity receptor VEGFR-2 in the human forebrain and cerebellum at developmental stages from 14 weeks' gestation (WG) to the13th postnatal month. Tissue samples free of detectable neuropathologic abnormalities were assessed by immunohistochemistry and confocal microscopy using anti-human VEGF and VEGFR-2 antibodies. The VEGFR-2 was first expressed in the whole cerebral mantle and in migrating cells in the intermediate zone, whereas VEGFwas found in superficial layers of the cortical plate, in radial glia, and in the cerebellar external germinal cell layer. From 23 WG, temporospatial VEGFR-2 expression was superimposable on that ofVEGF in the cortical plate, intermediate zone, basal ganglia, limbicstructures, and external germinal cell layer. The VEGF/VEGFR-2-positive astrocytes were observed during their generation and migration from 23 WG to the first postnatal month. The VEGF-positive mature oligodendrocytes were observed in myelinating structures in the forebrain from birth and in the cerebellum from 24WG. These data suggest that VEGF and VEGFR-2 are likely involved in several aspects of human brain development.