Vascular endothelial growth factor (VEGF) modulates vascular permeability and inflammation in rat brain
| Autor: | Edward H. Oldfield, Marsha J. Merrill, Martin A. Proescholdt, John D. Heiss, Maurizio C. Capogrossi, Judith Mühlhauser, Stuart Walbridge |
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| Rok vydání: | 1999 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty medicine.medical_treatment Inflammation Vascular permeability Endothelial Growth Factors Biology Blood–brain barrier Pathology and Forensic Medicine Cellular and Molecular Neuroscience chemistry.chemical_compound Neuritis Internal medicine Glioma medicine Animals Infusion Pumps Lymphokines Vascular Endothelial Growth Factors Growth factor Lymphokine Brain General Medicine medicine.disease Rats Inbred F344 Rats Vascular endothelial growth factor Vascular endothelial growth factor A Endocrinology medicine.anatomical_structure Neurology chemistry Blood-Brain Barrier Autoradiography Neurology (clinical) medicine.symptom |
| Zdroj: | Journal of neuropathology and experimental neurology. 58(6) |
| ISSN: | 0022-3069 |
| Popis: | 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 approximately 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.beta gal virus). BBB disruption in AdCMV.VEGF-treated brains was accompanied by a severe inflammatory response not observed in brains receiving AdCMV.beta gal or VEGF protein infusion, indicating that neither VEGF nor viral particles alone were responsible for the inflammatory response. However, injection of AdCMV.beta gal 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. |
| Databáze: | OpenAIRE |
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