Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats.
The active lesions in multiple sclerosis (MS) are characterized by blood-brain-barrier (BBB) breakdown, upregulation of adhesion molecules on capillary endothelial cells, and perivascular inflammation, suggesting that altered vessel permeability and activated endothelial cells are involved in the pathogenesis of the disease. Vascular endothelial growth factor (VEGF) mediates multiple aspects of blood vessel physiology, including regulation of growth, permeability, and inflammation. To investigate a possible relationship between VEGF expression and CNS autoimmune disease, we examined VEGF expression in MS plaques compared to normal white matter by immunohistochemistry and in situ hybridization. VEGF expression was consistently upregulated in both acute and chronic MS plaques. We also examined VEGF expression during the course of experimental allergic encephalomyelitis (EAE) in rats. VEGF-positive cells with astrocytic morphology increased in the spinal cord during the development of EAE and were found in association with inflammatory cells. Furthermore, intracerebral infusion of VEGF in animals previously immunized with myelin basic protein induced an inflammatory response in the brain, whereas infusion of vehicle, or infusion of VEGF in naive animals, did not. These results suggest that overexpression of VEGF may exacerbate the inflammatory response in autoimmune diseases of the CNS by inducing focal BBB breakdown and migration of inflammatory cells into the lesions.
Proescholdt
Martin A
MA
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1414, USA.
Jacobson
Steven
S
Tresser
Nancy
N
Oldfield
Edward H
EH
Merrill
Marsha J
MJ
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D004660:Encephalitis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007700:Kinetics; D008222:Lymphokines / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors