title: Angiogenesis is present in experimental autoimmune encephalomyelitis and pro-angiogenic factors are increased in multiple sclerosis lesions.
abstract: BACKGROUND
  Angiogenesis is a common finding in chronic inflammatory diseases; however, its role in multiple sclerosis (MS) is unclear. Central nervous system lesions from both MS and experimental autoimmune encephalomyelitis (EAE), the animal model of MS, contain T cells, macrophages and activated glia, which can produce pro-angiogenic factors. Previous EAE studies have demonstrated an increase in blood vessels, but differences between the different phases of disease have not been reported. Therefore we examined angiogenic promoting factors in MS and EAE lesions to determine if there were changes in blood vessel density at different stages of EAE.
  
  
  METHODS
  In this series of experiments we used a combination of vascular casting, VEGF ELISA and immunohistochemistry to examine angiogenesis in experimental autoimmune encephalomyelitis (EAE). Using immunohistochemistry we also examined chronic active MS lesions for angiogenic factors.
  
  
  RESULTS
  Vascular casting and histological examination of the spinal cord and brain of rats with EAE demonstrated that the density of patent blood vessels increased in the lumbar spinal cord during the relapse phase of the disease (p < 0.05). We found an increased expression of VEGF by inflammatory cells and a decrease in the recently described angiogenesis inhibitor meteorin. Examination of chronic active human MS tissues demonstrated glial expression of VEGF and glial and blood vessel expression of the pro-angiogenic receptor VEGFR2. There was a decreased expression of VEGFR1 in the lesions compared to normal white matter.
  
  
  CONCLUSIONS
  These findings reveal that angiogenesis is intimately involved in the progression of EAE and may have a role in MS.
authors.affiliation: Department of Autoimmunity, Transplantation and Inflammation, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Seabrook
authors.forename: Amanda
authors.initials: A
authors.lastname: Littlewood-Evans
authors.forename: Volker
authors.initials: V
authors.lastname: Brinkmann
authors.forename: Bernadette
authors.initials: B
authors.lastname: Pöllinger
authors.forename: Christian
authors.initials: C
authors.lastname: Schnell
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hiestand
mesh_terms: D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D051381:Rats; D011917:Rats, Inbred Lew; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2