Vascular endothelial growth factor (VEGF) modulates vascular permeability and inflammation in rat brain

Martin A. Proescholdt, John D. Heiss, Stuart Walbridge, Judith Mühlhauser, Maurizio C. Capogrossi, Edward H. Oldfield, Marsha J. Merrill

Research output: Contribution to journalArticlepeer-review


Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that also induces vascular permeability and macrophage migration. VEGF expression is weak in normal adult brain, but is strongly upregulated in glioma cells and reactive astrocytes, suggesting that chronic overexpression of VEGF in the brain contributes to blood-brain barrier (BBB) breakdown. We examined the effects of chronic VEGF overexposure on the integrity of the BBB using the following approaches: 1) continuous intracerebral infusion of VEGF via miniosmotic pump; and 2) intracerebral injection of an adenoviral vector encoding the VEGF165 gene (AdCMV. VEGF). After 6 days both treatments produced ~10-fold breakdown of the BBB (as measured by transport of 14C- aminoisobutyric acid (AIB) from blood into brain) compared with the respective controls (albumin infusion or AdCMV.βgal virus). BBB disruption in AdCMV. VEGF-treated brains was accompanied by a severe inflammatory response not observed in brains receiving AdCMV.βgal or VEGF protein infusion, indicating that neither VEGF nor viral particles alone were responsible for the inflammatory response. However, injection of AdCMV.βgal followed by VEGF infusion to the same site also elicited inflammation. Chronic overexposure of normal brain to VEGF also increased intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) class I and II expression. Although VEGF itself is not inflammatory, VEGF may modulate immune responses in the central nervous system (CNS) by opening the BBB, altering the immunoprivileged status of the brain, and allowing contact between normally sequestered CNS antigens and blood-borne immune mediators.

Original languageEnglish
Pages (from-to)613-627
Number of pages15
JournalJournal of Neuropathology and Experimental Neurology
Issue number6
Publication statusPublished - 1999


  • Adenovirus
  • Blood-brain barrier
  • Brain edema
  • Inflammation
  • Major histocompatibility complex
  • Vascular permeability factor
  • VEGF

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)


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