Inhibition of NADPH oxidase activation reduces EAE-induced white matter damage in mice.
J Neuroinflammation
; 12: 104, 2015 May 28.
Article
en En
| MEDLINE
| ID: mdl-26017142
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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Banco de datos:
MEDLINE
Asunto principal:
Médula Espinal
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Encéfalo
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NADPH Oxidasas
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Encefalomielitis Autoinmune Experimental
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Leucoencefalopatías
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Glicoproteína Mielina-Oligodendrócito
Límite:
Animals
Idioma:
En
Año:
2015
Tipo del documento:
Article