Abstracts

Rationale: Mesial temporal lobe epilepsy (MTLE) is one of the most prevalent types of partial epilepsy. Although many antiepileptic drugs (AEDs) are currently available to control ictogenesis, MTLE remains one of the most refractory forms of partial epilepsy. In this study, we analysed the impact of levetiracetam (LTM) and lacosamide (LCM) in the pilocarpine model of MTLE. Methods: Sprague-Dawley rats (250-275 g; n=27) were injected with scopolamine methylnitrate (1 mg/kg i.p.) and 30 min later with a single dose of pilocarpine hydrochloride (380 mg/kg, i.p) to induce a status epilepticus (SE) that was stopped after 1 hour with diazepam (5 mg/kg, s.c) and ketamine (50 mg/kg, s.c.). Twelve of 27 rats were used as controls and were not given any anti-epileptic drugs, 7 were treated with LTM (300 mg/kg/day) and 8 were treated with LCM (30 mg/kg/day). Three days after SE, rats were implanted with bipolar electrodes in the CA3 region of the hippocampus, entorhinal cortex (EC), dentate gyrus (DG) and subiculum (Sub) and EEG-video monitored. Interictal spikes, seizures and high-frequency oscillations were analysed from day 4^th to day 14^th after SE. Results: We found that the average duration of the latent period was 6.25 (± 1) days in controls, 5.3 (± 0.3) days in the LTM group, and 11 (± 1) days in the LCM group. During the latent period, animals treated with LTM or LCM showed significantly lower rates of interictal spikes and of interictal spikes with ripples compared to the control group, in the DG and Sub (p < 0.05). Rates of interictal spikes with fast ripples in the DG were also lower in the LCM group compared to controls (p < 0.05) and rates of interictal spikes with fast ripples in the Sub were also lower in the LTM and LCM group than in controls (p < 0.05). Conclusions: Our findings indicate that both drugs have structure- and event-specific effects during the latent period and suggest that they modify limbic network excitability underlying MTLE. Besides their anti-ictogenic properties, LTM and LCM may thus have disease-modifying properties in the pilocarpine model of MTLE.