title: Antibody neutralization of vascular endothelial growth factor (VEGF) fails to attenuate vascular permeability and brain edema in experimental pneumococcal meningitis.
abstract: To determine the contribution of vascular endothelial growth factor (VEGF) to cerebral edema formation in bacterial meningitis, we used a VEGF neutralizing antibody to block VEGF in rabbits, following induction of meningitis by intracisternal inoculation with 10(9) heat-killed pneumococci. At 8 h, cerebrospinal fluid (CSF) VEGF was significantly elevated in infected untreated animals, and correlated with CSF white blood cell (WBC) count (r=0.56, P=0.004), and brain water content (r=0.42, P=0.04). Blocking of VEGF did not attenuate brain edema, blood-brain barrier disruption, or CSF pleocytosis. The functional role of VEGF in the pathophysiology of BM remains elusive.
authors.affiliation: Wilhelmina Children's Hospital, University Medical Center, Room KE 04.1331, P.O. Box 85090, 3508 AB Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van der Flier
authors.forename: F E
authors.initials: FE
authors.lastname: Coenjaerts
authors.forename: P N
authors.initials: PN
authors.lastname: Mwinzi
authors.forename: E
authors.initials: E
authors.lastname: Rijkers
authors.forename: M
authors.initials: M
authors.lastname: Ruyken
authors.forename: J
authors.initials: J
authors.lastname: Scharringa
authors.forename: J L L
authors.initials: JL
authors.lastname: Kimpen
authors.forename: A I M
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: S P M
authors.initials: SP
authors.lastname: Geelen
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001929:Brain Edema / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000503:physiopathology*; D002199:Capillary Permeability / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002946:Cisterna Magna; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D008586:Meningitis, Pneumococcal / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000503:physiopathology*; D051379:Mice; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D014882:Water-Electrolyte Balance
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab