Phosphodiesterase-5 inhibition promotes remyelination by @entity8929 / XXXX and @entity1235 regulation in a @entity18 -induced @entity17 model.

@entity17 @entity8929 @entity19 @entity635 @entity18 @entity1021 @entity13766 @entity7855 @entity1235 @entity179 @entity10927 @entity15 @entity5579
UNASSIGNED: While it has recently been shown that @entity7855 (Viagra  ) has a protective effect on myelination/remyelination, the mechanism of this protection is still unknown. In general, cytokines, chemokines and metalloproteinases have a pro-inflammatory action, but can also exert a role in modulating glial cell activation, contributing to the balance of cell response. Investigating these molecules can contribute to clarifying the mechanisms of @entity7855 neuroprotection. In addition, it is not known whether @entity7855 is able to restore an already installed neurodegenerative process or if the treatment period is critical for its action. The aim of the present study was to evaluate, in a @entity18 ( @entity5579 )-induced @entity17 model, the effects and mechanisms of time-dependent treatment with @entity7855 (beginning 15days after @entity179 and continuing for 15days, or @entity1021 concomitantly with @entity179 and continuing for 30days) on neuroinflammation and remyelination. Neuroinflammation and @entity17 induced by @entity5579 in rodents has been widely used as a model of @entity15 ( @entity15 ). In the present study, five male C57BL/6 @entity19 aged 7-10weeks were used per group. For four weeks, the groups received either @entity18 ( @entity5579 ) 0.2% mixed in feed or @entity5579 combined with the administration of @entity7855 (Viagra  , Pfizer, 25mg/kg) orally in drinking water, @entity1021 concurrently with (sild-T0) or 15days (sild-T15) after the start of @entity5579 treatment. Control animals received pure food and water. The cerebella were dissected and processed for immunohistochemistry, immunofluorescence (frozen), Western blotting, Luxol fast blue staining and transmission electron microscopy. Magnetic resonance was performed for live animals, after the same treatment, using @entity5579 0.3%. @entity5579 induced an increase in the expression of @entity635 and a decrease in @entity8929 , @entity13766 , @entity10927 and GST-pi, as well as promoting damage in the structure and ultra-structure of the myelin sheath. Interestingly, the administering of sild-T0 promoted a further increase of @entity1235 , @entity8929 , and @entity13766 , possibly contributing to changes in the microglia phenotype, which becomes more phagocytic, cleaning myelin debris. It was also observed that, after sild-T0 treatment, the expression of GST-pi and @entity10927 increased and the myelin structure was improved. However, sild-T15 was not efficient in all aspects, probably due to the short treatment period and to @entity1021 after the installation of the degenerative process. Therefore, the present study shows that @entity7855 modulates inflammation, with the involvement of @entity1235 , @entity8929 , and @entity13766 , and also contributes to myelin repair. These protective effects were dependent on the therapeutic strategy used. This clarification can strengthen research proposals into the mechanism of action of @entity7855 and contribute to the control of @entity179 such as @entity15 .
