In Alzheimer's disease, which is characterized by chronic neuroinflammation, PPARγ activation attenuates neuroinflammation and augments expression of M2 macrophage markers, indicating that peripheral administration of PPAR agonists can influence an active and chronic inflammatory milieu in the CNS (Mandrekar-Colucci et al., 2012). PPAR activation is beneficial in other pathological conditions including TBI, SCI, EAE, stroke and ALS (Kiaei et al., 2005; Schutz et al., 2005; Drew et al., 2006; Sundararajan et al., 2006; Yi et al., 2008; Villapol et al., 2012). In EAE, infiltration of monocytes correlates with progression to the severe paralytic stages of disease (Ajami et al., 2011). Treating EAE animals with PPAR agonists is anti-inflammatory and slows disease progression; however, whether PPARs act solely by altering macrophage polarization in this model has not been confirmed (Niino et al., 2001; Diab et al., 2002, 2004; Feinstein et al., 2002; Gocke et al., 2009).
