Antibody neutralization of vascular endothelial growth factor (VEGF) fails to attenuate vascular permeability and brain edema in experimental pneumococcal meningitis.
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.
van der Flier
M
M
Wilhelmina Children's Hospital, University Medical Center, Room KE 04.1331, P.O. Box 85090, 3508 AB Utrecht, The Netherlands.
Coenjaerts
F E
FE
Mwinzi
P N
PN
Rijkers
E
E
Ruyken
M
M
Scharringa
J
J
Kimpen
J L L
JL
Hoepelman
A I M
AI
Geelen
S P M
SP
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
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab