Inhibition of NADPH oxidase activation reduces EAE-induced white matter damage in mice

Journal of Neuroinflammation

Sang Won Suh²  Tiina M Kauppinen¹  Tae Nyoung Chung³  Mackenzie Stevenson¹  Min Sohn⁵  Eunhi Choi⁴  Bo Eun Lee²  Song Hee Lee²  In Yeol Kim²  A Ra Kho²  Jin Hee Kim²  Bo Young Choi² 

[1] Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada;Department of Physiology, College of Medicine, Hallym University, Chuncheon, South Korea;CHA Bundang Medical Center, School of Medicine, CHA University, Kyunggi do, South Korea;Chuncheon Sacred Heart Hospital, Department of Rehabilitation Medicine, College of Medicine, Hallym University, Chuncheon, South Korea;Department of Nursing, Inha University, Incheon, South Korea

关键词: Microglia;    Apocynin;    Reactive oxygen species;    NADPH oxidase;    Multiple sclerosis;    Experimental autoimmune encephalomyelitis;   

Others  :  1221982
DOI  :  10.1186/s12974-015-0325-5

 received in 2014-12-10, accepted in 2015-05-15,  发布年份 2015

【 摘 要 】

Background

To evaluate the role of NADPH oxidase-mediated reactive oxygen species (ROS) production in multiple sclerosis pathogenesis, we examined the effects of apocynin, an NADPH oxidase assembly inhibitor, on experimental autoimmune encephalomyelitis (EAE).

Methods

EAE was induced by immunization with myelin oligodendrocyte glycoprotein (MOG (35-55)) in C57BL/6 female mice. Three weeks after initial immunization, the mice were analyzed for demyelination, immune cell infiltration, and ROS production. Apocynin (30 mg/kg) was given orally once daily for the entire experimental course or after the typical onset of clinical symptom (15 days after first MOG injection).

Results

Clinical signs of EAE first appeared on day 11 and reached a peak level on day 19 after the initial immunization. The daily clinical symptoms of EAE mice were profoundly reduced by apocynin. The apocynin-mediated inhibition of the clinical course of EAE was accompanied by suppression of demyelination, reduced infiltration by encephalitogenic immune cells including CD4, CD8, CD20, and F4/80-positive cells. Apocynin reduced MOG-induced pro-inflammatory cytokines in cultured microglia. Apocynin also remarkably inhibited EAE-associated ROS production and blood–brain barrier (BBB) disruption. Furthermore, the present study found that post-treatment with apocynin also reduced the clinical course of EAE and spinal cord demyelination.

Conclusions

These results demonstrate that apocynin inhibits the clinical features and neuropathological changes associated with EAE. Therefore, the present study suggests that inhibition of NADPH oxidase activation by apocynin may have a high therapeutic potential for treatment of multiple sclerosis pathogenesis.

【 授权许可】

   
2015 Choi et al.; licensee BioMed Central.

【 图 表 】

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