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

Acta Neurochir Suppl. 2010:106:55-9. doi: 10.1007/978-3-211-98811-4_9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies / pharmacology*
  • Autoantigens / metabolism
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / growth & development*
  • Brain / anatomy & histology
  • Brain / growth & development*
  • Environment
  • Excitatory Amino Acid Transporter 2 / metabolism
  • Gene Expression Regulation / drug effects
  • Rats
  • Rats, Long-Evans
  • Vascular Endothelial Growth Factor A / immunology*
  • Vascular Endothelial Growth Factor A / pharmacology*

Substances

  • Antibodies
  • Autoantigens
  • Excitatory Amino Acid Transporter 2
  • Vascular Endothelial Growth Factor A
  • epidermolysis bullosa acquisita antigen