The enhanced oxidative stress and inflammatory responses in an ischemic brain are thought to contribute to neuronal death. The antioxidant and anti-inflammatory actions of PPARδ agonists have been observed in a variety of cell types, including astrocytes and microglia [32–35]. In particular, PPARδ can activate transcription of antioxidant genes, including catalase and superoxide dismutase (SOD) [36–38]. PPARδ can also control gene transcription independent of binding to PPREs. Transrepression is thought to underlie many of the anti-inflammatory effects of PPARδ. PPARδ can exert transrepression by directly interacting with nuclear factor-κB (NF-κB), thereby inhibiting activation of the proinflammatory transcription factor [38]. In addition, PPARδ exerts transrepression in macrophages by relocating the transcriptional repressor B-cell lymphoma protein 6 (Bcl-6) from PPARδ to the promoter regions of proinflammatory genes, including the vascular cell adhesion molecule-1 (VCAM-1) and the monocyte chemoattractant protein-1 (MCP-1) [39–41].
