Abstracts

Rationale: Animal models of acquired epileptogenesis have relied heavily on severe status epilepticus from either pilocarpine or kainic acid treatment. In these models, rodents are treated with single injections that typically evoke severe, repetitive seizures lasting many hours. In the present study, however, low doses of kainate were injected into animals with EEG recordings, and the injections were titrated to evoke only a few electrographic seizures, with the goal of trying to avoid severe prolonged status epilepticus.Methods: Adult male Sprague-Dawley rats (n=35) were implanted with cortical epidural EEG recording electrodes and allowed to recover for 1 week. To induce seizures, the rats were injected with repeated low doses of kainate (7.5 mg/kg) until an electrographic seizure with duration greater than 30 sec was obtained. Subsequently, chronic video-EEG data were collected for 2-week periods separated by 6-week intervals for up to a year. Animals that lost their skull caps and/or EEG signal were re-implanted.Results: The kainate injections often only caused a few repetitive seizures, usually with EEG spiking between the seizures. Of the 31 rats with kainate-induced seizures, 10 died during the 1-year experiment. During five 2-week recording sessions, 17 of 21 rats had at least one electrographic and/or motor seizure, but no seizures were detected in 21% (4/21). Approximately 28% (6/21) of the animals had low seizure rates (only 1-2 seizures per 2-week epoch), and 6 of these rats had at least one 2-week period with no detected seizures and 5 rats had a least one 2-week period with only 1 or 2 seizures. The remaining rats had higher seizure frequencies (2-490 per 2-week epoch), and most showed temporal progression.Conclusions: Using a novel model of kainate treatment titrated to minimize the number of seizures during status epilepticus, we found several epileptic animals with very low seizure rates, and these animals had one or more 2-week periods with no detectable seizures (or only 1-2 seizures). This suggests that one or even several 2 week periods of continuous video-EEG recording may be too little monitoring to detect epileptic animals with low seizure rates. Such rats in this study would have otherwise been considered to be non-epileptic, in spite of their clear evidence of seizures, but with a very low seizure rate. In the same cohort of kainate-treated rats, other animals had high seizure rates with a progressive increase in seizure frequency.