Abstracts

Rationale: Temporal lobe epilepsy (TLE) is one of the most common forms of partial epilepsy whereby recurrent seizures appear in early adulthood. There is often a history of an initial brain insult (such as febrile convulsions, encephalitis, or status epilepticus) years prior to the onset of seizures, which can originate from the hippocampus, the amygdala or entorhinal cortex and are often refractory to medication. The role of interictal discharges in epileptogenesis remain elusive. Using chronic rodent models of TLE, recent studies have demonstrated that interictal spikes and associated high-frequency oscillations (HFOs, 80-500 Hz) evolve during the latent and chronic periods. In this study, we used the pilocarpine-treated rat model to analyse the evolution of interictal spikes and HFOs in various limbic structures during the latent and chronic periods in an attempt to further elucidate the mechanisms leading to the establishment of epileptic networks in epilepsy. Methods: Adult Sprague-Dawley rats (n=3) were implanted with bipolar depth electrodes in the dentate gyrus, CA3 region, subiculum and entorhinal cortex, 2 days after an initial pilocarpine-induced SE (380 mg/kg, i.p.). Local field potential (LFP) recordings were then performed on a 24-hr basis with a continuous video-EEG monitoring system starting from the 3rd to the 15th day after SE. The morphology and the occurrence of interictal spikes were analysed at different time points during the latent (day 4) and chronic periods (day 15). Ripples (80-200 Hz) and fast ripples (250-500 Hz) were also analysed in the filtered LFPs. Results: Pilocarpine-treated rats began to express spontaneous, recurrent seizures 5 to 7 days following the initial status epilepticus. Analysis of interictal spikes within the CA3 region revealed two morphological subtypes. Type A spikes occurred at a frequency of 0.16 Hz, had an average duration of 766 ms (±157) and were characterized by a spike followed by a slow wave. Type B spikes on the other hand were shorter (average duration: 285ms ± 38), occurred at a frequency of 0.31 Hz and consisted of a single spike. In both the latent and chronic periods, interictal activity consisted predominantly of Type B spikes (latent period: 82% (±7); chronic period: 100% (±0.6)). However, Type A spikes, although less prominent, were present almost exclusively in the latent (23% (±15)) rather than the chronic period (0% (±1)). No significant changes in the duration of Type II spikes were observed between latent and chronic period. HFOs were observed in 62% of Type A and 51% of Type B spikes in the latent period. 44% of Type B spikes continued to exhibit HFOs in the chronic period. Conclusions: Changes in the pattern of interictal spikes occurs between the latent and chronic periods within the hippocampus of pilocarpine-treated rodents. This illustrates the dynamic process underlying epileptogenesis and may serve as a biomarker for the establishment of the epileptogenic network leading to seizures.