dc.creatorNunes A.K.D.S.
dc.creatorRaposo C.
dc.creatorLuna R.L.D.A.
dc.creatorCruz-Hofling M.A.D.
dc.creatorPeixoto C.A.
dc.date2012
dc.date2015-06-26T20:30:20Z
dc.date2015-11-26T14:29:52Z
dc.date2015-06-26T20:30:20Z
dc.date2015-11-26T14:29:52Z
dc.date.accessioned2018-03-28T21:33:09Z
dc.date.available2018-03-28T21:33:09Z
dc.identifier
dc.identifierCytokine. , v. 60, n. 2, p. 540 - 551, 2012.
dc.identifier10434666
dc.identifier10.1016/j.cyto.2012.06.011
dc.identifierhttp://www.scopus.com/inward/record.url?eid=2-s2.0-84866770267&partnerID=40&md5=c4c7025a62dc1cc58d1b7b642215eab1
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/97302
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/97302
dc.identifier2-s2.0-84866770267
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1246960
dc.descriptionSildenafil induces cGMP accumulation through phosphodiesterase-5 (PDE5) inhibition. cGMP-pathways protect oligodendrocytes and modulate astroglial and microglial reactions. Microglia and astrocytes play an important role in perpetuating multiple sclerosis (MS), a chronic inflammatory disease characterized by demyelination. Therefore, sildenafil can be a potential tool for MS treatment. The present study investigated the effects of sildenafil on the myelin structure and astrocyte/microglia-mediated neuroinflammation in an animal model of MS. Cuprizone-induced demyelination and neuroinflammation in rodents has been widely used as a model for MS. Herein, five male C57BL/6 mice (7-10. weeks old) were used per group. Over a 4-week period, the different groups received the following: (1) cuprizone (0.2%) mixed into the chow; (2) cuprizone in the chow and sildenafil (Viagra®; 3, 25 or 50. mg/kg) in the drinking water; or (3) pure chow and water (control group). Cerebella were analyzed using transmission electron microscopy, western blotting, immunohistochemistry and luxol fast blue staining. Cuprizone induced tissue damage, with an increase in GFAP, Iba-1 and COX-2 and demyelination in comparison to the control group. However, cuprizone did not affect the expression of cytokines (TNF-α, IFN-γ, IL-1β and IL-2). Sildenafil reduced GFAP (25 and 50. mg/kg) and Iba-1 expression (25. mg/kg) in comparison to the cuprizone group, indicating the modulation of astrocytes and microglia, respectively. Sildenafil preserved myelin and axons ultrastructure and strongly reduced IFN-γ, TNF-α, IL-1β, IL-2 and COX-2 expression in comparison to the control and/or cuprizone groups. The results demonstrate a protective effect of sildenafil in the cerebellum. Thus, well-designed clinical trials may demonstrate that the oral administration of sildenafil can be suitable for individuals with MS and other neuroinflammatory/neurodegenerative diseases, providing additional benefits to current treatments. © 2012 Elsevier Ltd.
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dc.languageen
dc.publisher
dc.relationCytokine
dc.rightsfechado
dc.sourceScopus
dc.titleSildenafil (viagra®) Down Regulates Cytokines And Prevents Demyelination In A Cuprizone-induced Ms Mouse Model
dc.typeArtículos de revistas


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