We showed that the current systemic treatment protocols with Wy-14643 or fenofibrate activated PPARα protein in the brain without LPS injection. In parallel, Wy-14643 and fenofibrate also elevated mRNA level of PPARα. LPS injection into the somatosensory cortex decreased the mRNA level of PPARα and elevated many pro-inflammatory genes in the brain. Wy-14643 and fenofibrate inhibited the concomitant LPS-induced changes in the level of PPARα and pro-inflammatory molecules. Furthermore, these PPARα agonists attenuated subsequent microglia/macrophage activation, leukocyte recruitment, and neuronal injury. These findings suggest that PPARα activation attenuates neuroinflammation induced by LPS. This notion is consistent with a previous report that LPS-induced inflammation was augmented in PPARα null mice (Kono et al., 2009). Whether or not and how activated PPARα directly influences the gene expression of a variety of pro-inflammatory molecules is a research area that is being extensively studied (Daynes and Jones, 2002; Glass and Saijo, 2010).
