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

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. © 2015 choi et al.; licensee biomed central.