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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2015

Open Access 01-12-2015 | Research

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

Authors: Bo Young Choi, Jin Hee Kim, A Ra Kho, In Yeol Kim, Song Hee Lee, Bo Eun Lee, Eunhi Choi, Min Sohn, Mackenzie Stevenson, Tae Nyoung Chung, Tiina M Kauppinen, Sang Won Suh

Published in: Journal of Neuroinflammation | Issue 1/2015

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Abstract

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.
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Metadata
Title
Inhibition of NADPH oxidase activation reduces EAE-induced white matter damage in mice
Authors
Bo Young Choi
Jin Hee Kim
A Ra Kho
In Yeol Kim
Song Hee Lee
Bo Eun Lee
Eunhi Choi
Min Sohn
Mackenzie Stevenson
Tae Nyoung Chung
Tiina M Kauppinen
Sang Won Suh
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2015
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-015-0325-5

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