Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2013 (2013), Article ID 321460, 11 pages
Research Article

Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model

1Departamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Rua Monteiro Lobato 255, 13083-862 Campinas, SP, Brazil
2Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Av. Professor Moraes Rego, s/n, Cidade Universitária, 50670-420 Recife, PE, Brazil

Received 27 March 2013; Revised 12 June 2013; Accepted 13 June 2013

Academic Editor: Geeta Ramesh

Copyright © 2013 Catarina Raposo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


We recently demonstrated that sildenafil reduces the expression of cytokines, COX-2, and GFAP in a demyelinating model induced in wild-type (WT) mice. Herein, the understandings of the neuroprotective effect of sildenafil and the mediation of iNOS/NO system on inflammatory demyelination induced by cuprizone were investigated. The cerebella of iNOS−/− mice were examined after four weeks of treatment with cuprizone alone or combined with sildenafil. Cuprizone increased GFAP, Iba-1, TNF-α, COX-2, IL-1β, and IFN-γ expression, decreased expression of glutathione S-transferase pi (GSTpi), and damaged myelin in iNOS−/− mice. Sildenafil reduced Iba-1, IFN-γ, and IL-1β levels but had no effect on the expression of GFAP, TNF-α, and COX-2 compared to the cuprizone group. Sildenafil elevated GSTpi levels and improved the myelin structure/ultrastructure. iNOS−/− mice suffered from severe inflammation following treatment with cuprizone, while WT mice had milder inflammation, as found in the previous study. It is possible that inflammatory regulation through iNOS-feedback is absent in iNOS−/− mice, making them more susceptible to inflammation. Sildenafil has at least a partial anti-inflammatory effect through iNOS inhibition, as its effect on iNOS−/− mice was limited. Further studies are required to explain the underlying mechanism of the sildenafil effects.