Role of vascular endothelial growth factor in blood-brain barrier breakdown and angiogenesis in brain trauma.
The role of vascular endothelial growth factor (VEGF) in blood-brain barrier (BBB) breakdown and angiogenesis, observed previously in the cerebral cortical cold-injury model, was investigated. Immunohistochemistry was used to assess BBB permeability to plasma fibronectin and to localize VEGF protein in the cortical cold-injury model over a period of 10 min to 14 days post-injury. BBB breakdown to fibronectin in lesion vessels was observed at 10 min post-injury, was maximal between 2 and 4 days and declined gradually thereafter, while occasional perilesional vessels remained permeable up to 6 days. Increased VEGF immunoreactivtiy occurred later-it was observed in pial vessels after 6 hours (h), and persisted up to day 14. Arterioles within the cold lesion showed VEGF immunoreactivity at 36 h, thus preceding the onset of endothelial proliferation and angiogenesis that occurred from day 3 to day 5. VEGF immunoreactivity was also observed in inflammatory cells and astrocytes. These results indicate that the immediate breakdown of the BBB in the cold lesion is unrelated to VEGF. The presence of mural VEGF in permeable pial vessels and lesional arterioles suggests that VEGF is one of several factors that mediates BBB breakdown in this model. The association of maximal VEGF immunoreactivity with endothelial proliferation and neovascularization suggests that VEGF promotes angiogenesis and repair following brain trauma.
Nag
S
S
Department of Pathology, University of Toronto, Ontario, Canada.
Takahashi
J L
JL
Kilty
D W
DW
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001808:Blood Vessels / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D002199:Capillary Permeability; D003080:Cold Temperature; D016228:Endothelial Growth Factors / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D005353:Fibronectins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors