NFκB activity and target gene expression in the rat brain after one and two exposures to ionizing radiation

The central nervous system injury that can result after radiotherapy has been suggested to involve induced gene expression and cytokine production. We have previously shown that irradiation of primary cultures of rat astrocytes results in the activation of NFκB. To determine whether such an effect also occurs in vivo, NFκB activity was analyzed in the cerebral cortex of the rat brain after whole body irradiation. After a single dose of 15 Gy, NFκB activity was increased by 2 h postirradiation, returning to unirradiated levels by 8 hours. The increase was dose-dependent beginning at 2 Gy and continuing to at least 22.5 Gy. NFκB activity in the irradiated cortex was not accompanied by IκBα degradation. When 7.5 Gy was delivered 24 h before the 15 Gy, the increase in NFκB activity after 15 Gy was significantly reduced. These results suggest that an initial exposure to radiation induced a refractory period in the brain during which the susceptibility of NFκB to activation by subsequent irradiation was significantly reduced. This period of reduced sensitivity to radiation was also apparent for the induction of the NFκB-regulated cytokines IL-1β, IL-6, and TNFα.