Figure 4

Role of PPAR-α in simvastatin-induced inhibition of TNF-α and IL-1β after SCI WT mice show a significant production of cytokines at 24 hours after SCI (h, i). Cytokine levels were significantly enhanced in injured-PPAR-α KO mice (h, i). Treatment with simvastatin significantly reduced the spinal cord TNF-α and IL-1β (i) production. The genetic absence of the PPAR-α receptor significantly blocked the effect of simvastatin treatment (h, i). Data are means ±S.E. mean of 10 mice for each group. *P < 0.01 vs. Sham; °P < 0.01 vs. SCI-WT group; °°P < 0.01 vs. simvastatin-treated WT group. In addition, tissue sections obtained from PPAR-αWT animals at 24 h after SCI demonstrate positive staining for TNF-α when compared with spinal cord tissue collected from PPAR-α sham-operated mice (a, d and g) The intensity of the positive staining for TNF-α was markedly increased in tissue section from injured-PPAR-αKO mice (e, g). Section from simvastatin-treated PPAR-αWT mice did not reveal positive staining for TNF-α (c, g) The genetic absence of the PPAR-α significantly blocked the effect of simvastatin on the TNF-α expression (f, g). Data are means ± SEM of 10 mice for each group. The assay was carried out by using Imaging Densitometer (AxioVision, Zeiss, Milan, Italy). Data are expressed as % of total tissue area. This figure is representative of at least 3 experiments performed on different experimental days. *P < 0.01 vs. Sham; °P < 0.01 vs. SCI-WT group; °°P < 0.01 vs. simvastatin-treated WT mice. ND: not detectable.