Spinal cord injury (SCI) is associated with altered conduction of axons and motor dysfunction due to oligodendrocyte and neuronal cell death [85]. SCI is accompanied by inflammation and edema, which results in infiltration of inflammatory cells, release of proinflammatory factors, vascular permeability, and ultimately necrosis [86, 87]. Data suggest that PPARδ can modulate these responses. Administration of GW0742 to mice after SCI significantly improved their motor function. The PPARδ antagonist, GSK0660, blocked the effect of GW0742 on motor function suggesting that the protective effects of the agonists are dependent on activation of the PPARδ receptor. The effects of GW0742 were associated with reduced oxidative stress and proinflammatory responses in the spinal cord. This included a reduction in (i) TNF-α, IL-1β, and iNOS expression, (ii) NF-κB activation, (iii) neutrophil infiltration, (iv) nitrotyrosine and lipid peroxidation, (v) FasL expression, and (vi) TUNEL staining [23]. In accord with these findings, data demonstrate that GW0742 administered 1 hour prior to SCI reduced cell death and inflammation in cultured murine spinal cord slices. The reduction in inflammation included decreased (i) Cox-2 expression and (ii) p38 MAPK, c-Jun N-terminal kinase, and NF-κB activation [88].
