title: Reduction of microglial activity in a model of multiple sclerosis by dipyridamole.
abstract: BACKGROUND
  Despite extensive and persistent activation of microglia in multiple sclerosis (MS), microglia inhibitors have not yet been identified for treatment of the disorder. We sought to identify medications already in clinical use that could inhibit the activation of microglia. On the basis of the reported inhibitory effects of dipyridamole on phosphodiesterase activity that result in the production of various anti-inflammatory outcomes, we selected it for study. Dipyridamole is used clinically for secondary prevention in stroke. In this study, dipyridamole was examined using microglia in culture and in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE).
  
  
  RESULTS
  We found that dipyridamole attenuated the elevation of several cytokines and chemokines in human microglia caused by Toll-like receptor stimulation. Morphological characteristics of activated microglia in culture were also normalized by dipyridamole. In mice, dipyridamole decreased the clinical severity of EAE and reduced microglial activity and other histological indices of EAE in the spinal cord.
  
  
  CONCLUSIONS
  Dipyridamole is an inhibitor of microglia activation and may have a role in MS and other neurological conditions to attenuate microglial activity.
authors.affiliation: Hotchkiss Brain Institute and the Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Drive, Calgary, AB T2N 4N1, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Sloka
authors.forename: Luanne M
authors.initials: LM
authors.lastname: Metz
authors.forename: Walter
authors.initials: W
authors.lastname: Hader
authors.forename: Yves
authors.initials: Y
authors.lastname: Starreveld
authors.forename: V Wee
authors.initials: VW
authors.lastname: Yong
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis; D004176:Dipyridamole / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D008070:Lipopolysaccharides; D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D000255:Adenosine Triphosphate