Injured axons have a limited capacity to spontaneously regenerate. Therefore, interventions that enhance or stimulate axon growth may further increase recovery or minimize the functional deficits caused by CNS injury. A few studies have reported that PPAR activation promotes axonal growth in neuronal cell lines and primary DRG (dorsal root ganglion) neuron cultures. Specifically, the PPARγ agonists pioglitazone and 15d-PGJ2 increase the number and lengths of neurites (Jung et al., 2003; Miglio et al., 2009). These effects may occur through modulating RhoA, which is increased in injured neurons and limits axon regeneration after CNS injury (Dubreuil et al., 2003; Madura et al., 2004). Ibuprofen (which activates PPARγ at micromolar levels) inhibits RhoA and stimulates corticospinal and serotonergic axon sprouting after spinal cord transection in rats (Lehmann et al., 1997; Fu et al., 2007). Work by others showed that the growth-promoting effects of ibuprofen involved PPARγ activation and its ability to inhibit RhoA activation (Dill et al., 2010). This effect may be mediated by SHP-2 (Src homology region 2-containing protein tyrosine phosphatase-2), which is involved in the PPARγ-dependent inhibition of RhoA
