Reduction of microglial activity in a model of multiple sclerosis by dipyridamole

Journal of Neuroinflammation

V Wee Yong¹  Yves Starreveld¹  Walter Hader¹  Luanne M Metz¹  Scott Sloka¹ 

[1] Hotchkiss Brain Institute and the Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Drive, Calgary, AB T2N 4N1, Canada

关键词: Microglia;    Macrophage;    Inhibitor;    EAE;    Cytokine;   

Others  :  1152482
DOI  :  10.1186/1742-2094-10-89

 received in 2013-06-14, accepted in 2013-07-02,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Sloka et al.; licensee BioMed Central Ltd.

【 图 表 】

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