Effects of VEGF administration or neutralization on the BBB of developing rat brain

Abstract

We investigated the effects of exogenous Vascular Endothelial Growth Factor VEGF combined with an enriched environment on BBB integrity after a minimal trauma induced during the first days of the critical visual period in rats, when peak levels of endogenous VEGF secretion are reached. VEGF was administered using osmotic mini-pumps placed in middle cortical layers of P18 Long-Evansrats. Tissue changes were evaluated using conventional histology. BBB integrity was shown by immunohistochemistry techniques for EBA and GluT-1. Mini-pump implantation produced a wider cavity in anti-VEGF infused rats. In VEGF-infused rats there was a damaged region around the cannula that was smaller in rats raised in an enriched environment (EE). The administration of VEGF induced a high concentration of plasma proteins in the neuropil around the point of cannula placement and a high inflammatory reaction. VEGF-infused rats raised in an EE showed a lower degree of extravasation and better tissue preservation. Anti-VEGF administration produced a lower protein expression profile and more widespread deterioration of tissue. Double immunofluorescence for EBA and GluT-1 showed that the administration of VEGF preserves the tissue, which remains present but not fully functional. In contrast, a combination of VEGF administration and an EE partially protects the functionally damaged tissue with a higher preservation of BBB integrity. © 2009 Springer-Verlag Vienna.