Although studies have not examined if PPARδ agonists can modulate radiation-induced cognitive impairment, data demonstrate that PPARγ can ameliorate or prevent radiation-induced cognitive decline. In particular, pioglitazone ameliorated radiation-induced cognitive impairment when administered prior to, during, and for 4 or 54 weeks after fWBI of young adult male rats [83]. While these results are promising, there are concerns with using pioglitazone in the clinic, including an increased risk of (i) weight gain and (ii) myocardial infarctions [84]. It is important to investigate if, similar to PPARγ, PPARδ can modulate radiation-induced cognitive impairment. Since PPARδ is the primary subtype in the CNS, it is possible that PPARδ agonists can mediate a more pronounced antioxidant and anti-inflammatory response in the brain.
