Abstracts

RATIONALE: Ionizing radiation at doses ? 30 Gy reportedly diminishes focal epileptogenicity, both clinically and in some experimental epilepsy models. We have investigated whether such effects occur in amygdala-kindled rats at various doses within this dosage range and as a function of kindling progression. We did not observe significant reductions in either seizure threshold or seizure duration using this model and instead observed subtle increases in excitability, which varied as a function of both radiation dose and kindling progression. METHODS: Male Wistar rats were kindled by daily (afterdischarge threshold) electrical stimulation of the left amygdala. Generalized seizure thresholds (GST) were determined on three consecutive days preirradiation and at weekly intervals postirradiation for a period of six months. The left amygdala was irradiated via dorsoventral exposure to a beam-collimated 18MV x-ray source, with a 2.5 mm radius (90% isodose). Experimental groups received isocenter doses of 10, 18, 25 or 30 Gy, delivered either prekindling, upon reaching stage 3, upon reaching stage 5, or following 10 stage 5 seizures. Controls were sham irradiated. RESULTS: No significant changes in GST or seizure duration were observed for any of the radiation doses or at any of the time-points examined. No significant changes in the rate of kindling were observed as a function of irradiation. The incidence of secondary convulsions was both increased and decreased significantly as a complex function of both radiation dose and seizure progression. CONCLUSIONS: We conclude that the threshold and severity of amygdala-kindled seizures are not reduced following exposure to ionizing radiation at doses ? 30 Gy. In light of a recent report that analogous radiation exposures reduce seizure frequency in rats following focal injection of kainic acid, we conclude that such effects may be specific to models exhibiting spontaneous seizure initiation. The absence of seizure reduction in our kindling model might therefore be explained on the basis that these seizures are initiated by strictly artificial means. We are presently investigating this possibility using hybrid epilepsy models.