The beneficial effects of PPAR activation have been independently reproduced in many rodent models of traumatic injury and neurodegenerative disease and there are several potential mechanisms through which PPAR activation promotes CNS repair and functional recovery. Activation of PPARs can reduce inflammation and confer neuroprotection, in part through their ability to minimize cell death and reduce mitochondrial dysfunction. PPAR activation may also enhance axonal growth and remyelination. Through non-genomic mechanisms, PPAR agonists may have analgesic effects. Since the pathophysiology of traumatic CNS injury and neurodegeneration is dynamic, the timing of PPAR activation likely needs to be tailored to meet the specific characteristics of the disease in question. Still, the broad effects on overlapping mechanisms of neurologic injury make these drugs very promising therapeutics for treating traumatic injuries to the brain or spinal cord as well as various neurodegenerative diseases.
