Ongoing studies in our laboratory are investigating the ability of PPARδ to modulate radiation-induced brain injury. Incubating BV-2 murine microglial cells with the PPARδ agonist, L-165041, is effective at modulating radiation-induced injury, including inhibiting the radiation-induced increase in (i) intracellular ROS generation, (ii) Cox-2, iNOS and MCP-1 expression, (iii) IL-1β and TNF-α message levels, and (iv) NF-κB and AP-1 activation (unpublished results). These observations demonstrate the important antioxidant and anti-inflammatory actions of PPARδ agonists in microglial cells following irradiation and are similar to previous findings indicating that the PPARα agonists, GW7647 and fenofibrate, can inhibit radiation-induced inflammatory markers in BV-2 cells [82].
