Enhanced excitability induced by ionizing radiation in the kindled rat

Evidence derived from both clinical and experimental investigations has suggested an influence of ionizing radiation on focal epileptogenicity. To better characterize this influence we applied focal ionizing radiation to a kindled epileptic focus in the rat amygdala. The right and left basolateral amygdala and right frontal cortex were implanted with concentric bipolar electrodes. Rats were kindled through a minimum of 10 stage 5 seizures by afterdischarge-threshold electrostimulation of the left amygdala, after which generalized seizure thresholds were determined prior to irradiation. The left amygdala was exposed to single-fraction central-axis doses of either 18 or 25 Gy using a beam-collimated (60)Co source (1.25 MeV). Generalized seizure thresholds were then redetermined at weekly intervals for 10 weeks and at monthly intervals for an additional 3 months. We observed no significant changes in seizure threshold during the postirradiation interval; however, we did observe persistent changes in seizure dynamics manifesting within the first week postirradiation. These consisted of an increased tendency for seizure activity to propagate into brain stem circuits during the primary ictus (i.e., "running fits") and an increased tendency for secondary convulsions to emerge postictally. These effects involving seizure dynamics have not been reported previously and appear to represent a radiation-induced disinhibition of one or more neural circuits. The disparity between these effects and earlier reports of seizure-suppressive effects resulting from analogous radiation exposures is discussed in relation to kindling and status epilepticus-induced pathogenesis within the hippocampus.