Abstracts

The elderly have an enhanced incidence and prevalence of seizure disorders with up to 50% of cases having no identifiable antecedent. This has lead to the hypothesis that aging of the central nervous system (CNS) itself may be epileptogenic. To begin to assess this hypothesis, our laboratory compared the susceptibility of adult and aged rats to kainate-induced seizures and status epilepticus. This study revealed that aged rats have a greater frequency of wet-dog shakes and shorter latencies to onset for all classes of seizures and status epilepticus during systemic kainate-treatment. This experiment did not, however, distinguish whether this aging-related change is due to altered pharmacokinetics, blood brain barrier, and/or pharmacodynamics. Consequently, in this study the threshold for kainate induced seizures was examined in vitro., Hippocampal slices from adult (4-8 mo.) and aged (22-26 mo.) Fischer 344 rats were examined using field potential recordings from CA3 to assess activity evoked with single or paired orthodromic stimuli. The threshold for kainate-induced epileptiform activity was examined by increasing the kainate concentration (12.5, 25, 50, and 100 nM) while monitoring evoked and spontaneous activity., In aCSF, no difference in the maximal amplitude of the evoked response was noted in aged (n = 24; 6.6 [plusmn] 0.6 mV) vs. adult slices (n = 25; 6 [plusmn] 0.5 mV; p [gt] 0.4; ANOVA). Evoked activity usually entailed a population spike followed by a positive field potential shift that often had a secondary small amplitude spike. In two of the aged slices, but none of those from adults, stimulating at a supra maximal intensity elicited an epileptiform burst. When paired stimuli were delivered using a 50 ms interpulse interval, 92% of aged slices (n = 13) and 31% of adult slices (n = 16) showed facilitation of the second spike (p [lt] 0.001; chi-square). To assess the threshold for kainate-induced epileptiform activity, 10 slices from adult and 10 slices from aged rats were examined. In total, 80% of adult and 90% of aged slices showed epileptiform activity by the time the kainate concentration reached 100 nM. The kainate concentrations required for evoked (9.7 [plusmn] 2.8 nM vs. 21.9 [plusmn] 4.6 nM; p [lt] 0.05; ANOVA) and spontaneous (20.3 [plusmn] 4.7 nM vs. 34.4 [plusmn] 4.6 nM; p [lt] 0.05; ANOVA) epileptiform activity were significantly lower in slices from aged rodents, compared to adults., These data indicate that the aged CNS itself has an enhanced susceptibility to kainate-induced epileptiform activity that could contribute to the increase in wet-dog shakes and reduced latency to onset for class I/ II seizures and status epilepticus in aged rodents during systemic kainate treatment. Further, if these pharmacodynamic changes also occur in the human CNS during aging, they could contribute to the increased incidence and prevalence of idiopathic seizure disorders., (Supported by the Epilepsy Foundation of America and NIA.)