title: 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.
authors.affiliation: Department of Neuroscience, LaNCE, Clinical and Experimental Neuroscience Laboratory, University of Basque Country, Leioa, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Ortuzar
authors.forename: E G
authors.initials: EG
authors.lastname: Argandoña
authors.forename: H
authors.initials: H
authors.lastname: Bengoetxea
authors.forename: O
authors.initials: O
authors.lastname: Leis
authors.forename: S
authors.initials: S
authors.lastname: Bulnes
authors.forename: J V
authors.initials: JV
authors.lastname: Lafuente
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology*; D001324:Autoantigens / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000254:growth & development*; D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development*; D004777:Environment; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology* / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D001324:Autoantigens; D027342:Excitatory Amino Acid Transporter 2; D042461:Vascular Endothelial Growth Factor A; C044589:epidermolysis bullosa acquisita antigen