title: Therapeutic effects of dasatinib in mouse model of multiple sclerosis.
abstract: BACKGROUND
  Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. Dasatinib (Sprycel) is a selective protein tyrosine kinase inhibitor with immunomodulatory properties that abrogates multiple signal transduction pathways in immune cells. In the present research, our aim was to test the therapeutic efficacy of dasatinib in experimental model of MS.
  
  
  METHODS
  We performed EAE induction in female C57BL/6 mice by myelin oligodendrocyte glycoprotein(35-55) (MOG(35-55)) in Complete Freund's Adjuvant (CFA) emulsion, and used dasatinib for the treatment of EAE. During the course of study, clinical evaluation was assessed, and on day 21 post-immunization blood samples were taken from the heart of mice for tumor necrosis factor-alpha (TNF-α), nitric oxide (NO) and antioxidants capacity evaluation. The mice were sacrificed and brains and cerebellums of mice were removed for histological analysis. Also for in vitro analysis, we used C6 astrocytoma cell line to evaluate the inhibitory effects of dasatinib in cell proliferation and matrix metalloproteinase-2 (MMP-2) activity.
  
  
  RESULTS
  Our findings demonstrated that dasatinib had beneficial effects on EAE by lower incidence, attenuation in the severity and a delay in the onset of disease. The serum level of NO and TNF-α in dasatinib treated mice was significantly lower than control mice. In vitro, dasatinib inhibited cell proliferation and MMP-2 activity.
  
  
  CONCLUSIONS
  Dasatinib with its potential therapeutic effects and immunomodulatory properties may be recommended, after additional necessary tests and trials, for the treatment of MS.
authors.affiliation: Imam Hassan Mojtaba Hospital, Alborz University of Medical Sciences , Karaj , Iran .
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Azizi
authors.forename: Mahdi
authors.initials: M
authors.lastname: Goudarzvand
authors.forename: Sanaz
authors.initials: S
authors.lastname: Afraei
authors.forename: Reza
authors.initials: R
authors.lastname: Sedaghat
authors.forename: Abbas
authors.initials: A
authors.lastname: Mirshafiey
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000069439:Dasatinib / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D020778:Matrix Metalloproteinase 2 / Q000276:immunology; D051379:Mice; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009569:Nitric Oxide / Q000276:immunology; D010446:Peptide Fragments / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C445081:myelin oligodendrocyte glycoprotein (35-55); D009569:Nitric Oxide; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D000069439:Dasatinib
keywords: Dasatinib; experimental autoimmune encephalomyelitis; matrix metalloproteinase-2; multiple sclerosis; nitric oxide