Model for the role of PPARs in radiation-induced brain injury. Irradiation is hypothesized to modify the brain microenvironment via the generation of an inflammatory and/or oxidative stress response which is also characterized by increased cell death of the neural precursor cells residing in the neurogenic regions of the brain. This alteration in the microenvironment is proposed to play a role in the dysfunction of the various cell-types in the brain (e.g., astrocytes, endothelial cells, microglia, neurons, and oligodendrocytes) and the reduction in ongoing adult neurogenesis ultimately contributing to radiation-induced brain injury including cognitive impairment. Activation of PPARs using specific ligands is hypothesized to play a role in normalizing the brain microenvironment and preserving cellular function following irradiation in part via inhibition of proinflammatory signaling pathways and by upregulation of antioxidant enzyme activities thus ameliorating the detrimental effects of radiation on the brain.
