Influence of ionizing radiation on the course of kindled epileptogenesis

Several clinical and experimental reports suggest that low-dose irradiation of an established epileptic focus can reduce the occurrence of spontaneous seizures. Conversely, some recent reports suggest that under some conditions low-dose irradiation may have disinhibitory effects on seizure expression. Here, we have investigated mechanistic aspects of this phenomenon in the kindling model of epilepsy by applying focal irradiation at various points during kindling development. Rats were kindled to stage 5 by afterdischarge-threshold electrostimulation of the left amygdala. Treatment groups were irradiated using a collimated X-ray beam (18 MV) either prior to kindling, at kindling stage 3, or at kindling stage 5, by exposure of the left amygdala to a single-fraction central-axis dose of 25 Gy. Generalized seizure thresholds (GSTs) were subsequently assayed at weekly intervals for 10 weeks and at monthly intervals for an additional 3 months, along with the severity of the evoked seizures. Irradiation produced no significant effects on seizure threshold, but did produce persistent changes in seizure severity which varied as a function of the timing of irradiation. Relative to sham irradiated controls, the occurrence of stage 6 seizures was significantly increased by irradiation prior to kindling, but was unaffected by irradiation at kindling stage 3, and significantly reduced by irradiation at kindling stage 5. Quantitative immunohistochemical assays for neuron and astrocyte densities within the amygdala and hippocampus revealed only subtle changes in neuronal density within the dentate granule cell layer. These results are discussed in relation to mechanisms of seizure- and radiation-induced plasticity.