Angiogenesis in the brain during development: the effects of vascular endothelial growth factor and angiopoietin-2 in an animal model

OBJECT: The goal of this study was to examine the roles of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) in the formation of blood vessels in the brain in a developmental animal model not routinely used for such a study. METHODS: Either VEGF, Ang-2, or a combination of the two factors were injected into the optic tectum of 4-day-old quail embryos. Immunohistochemical analysis and laser confocal microscopy were used to observe the effects on endothelial cells in the brain. Vascular endothelial growth factor and Ang-2 had very different effects on the development of blood vessels; the former caused expansion and the latter retraction of these vessels. Treatment with a combination of VEGF and Ang-2 caused retroorbital or intraventricular hemorrhage, and brain blood vessels appeared enlarged and dysmorphic, with dramatically extended filopodia. CONCLUSIONS: Some of these observations may provide insight into how one may develop a better model of brain arteriovenous malformations.