VEGF and vascular changes in chronic neuroinflammation.
A vascular component has long been associated with the pathological changes in multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE). Despite the codependence of angiogenesis and many chronic inflammatory disorders, only circumstantial evidence is available to support the existence of angiogenesis in MS or EAE. To determine if angiogenesis occurs in conjunction with clinical and pathological signs of CNS inflammatory disease we evaluated temporal and spatial blood vessel counts, VEGF immunoreactivity, and histopathological changes in the spinal cord of guinea pigs with chronic-progressive (CP)-EAE (day 0-90 post-immunization, n=64) and controls (n=17). The number of vessels per section increased in infiltrated and demyelinated lesions by day 15 post-immunization and remained significantly higher than controls throughout the course of the disease. The number of vessels correlated with both clinical and pathological scores for inflammation, infiltration and demyelination. Vascular endothelial growth factor (VEGF) expression increased during acute disease peaking at day 26, which was the transition from the acute-inflammatory to chronic-demyelinating phase, before gradually returning to baseline levels. These observations implicate angiogenesis as a component of chronic neuroinflammation and demyelination and may suggest alternative therapeutic strategies for multiple sclerosis.
Kirk
S L
SL
Department of Pathology, The University of Western Ontario, 1151 Richmond Street, London, ON N6A 5C1, Canada.
Karlik
S J
SJ
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006168:Guinea Pigs; D020078:Neurogenic Inflammation / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A