title: Decreased expression of VEGF-A in rat experimental autoimmune encephalomyelitis and in cerebrospinal fluid mononuclear cells from patients with multiple sclerosis.
abstract: Vascular endothelial growth factor A (VEGF-A) stimulates angiogenesis, but is also pro-inflammatory and plays an important role in the development of neurological disease, where it can have both attenuating and exacerbating effects. VEGF-B, a related molecule, is highly expressed in the central nervous system and seems to be important in neurological injury. A few studies have indicated that VEGF-A may play a role in the pathogenesis of multiple sclerosis (MS), but the role of VEGF-B has not been studied. We have studied the expression of VEGF-A, -B and their receptors by mRNA in situ hybridization, immunohistochemistry and real-time PCR in spinal cord from LEW rats with experimental autoimmune encephalomyelitis (EAE) and in cerebrospinal fluid (CSF) and blood samples from MS patients. Whereas VEGF-A is downregulated in glia in EAE, the infiltrating inflammatory cells are positive for VEGF-A. Expression of VEGF-B and the VEGF receptors is unaltered. In addition, the levels of VEGF-A mRNA in mononuclear cells [corrected] in CSF are lower in MS patients compared with controls. These results demonstrate a complex regulation of VEGF-A during neuroinflammation and suggest that VEGF-B is not involved in the pathogenesis of MS.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. emma.tham@ki.se
authors.forename: E
authors.initials: E
authors.lastname: Tham
authors.forename: A W
authors.initials: AW
authors.lastname: Gielen
authors.forename: M
authors.initials: M
authors.lastname: Khademi
authors.forename: C
authors.initials: C
authors.lastname: Martin
authors.forename: F
authors.initials: F
authors.lastname: Piehl
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D000818:Animals; D002555:Cerebrospinal Fluid / Q000166:cytology; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D042561:Vascular Endothelial Growth Factor B / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D040281:Vascular Endothelial Growth Factor Receptor-1