Abstracts

Rationale: Mesio temporal lobe epilepsy (MTLE) is one of the most prominent forms of focal drug resistant epilepsy. A better understanding of mechanisms underlying this resistance would help to identify new active compounds. The morphological and electro-clinical features of MTLE have been observed in a mouse model after unilateral injection of kainic acid in the dorsal hippocampus, the MTLE mouse. In a previous study, we investigated the effect of the most commonly used antiepileptic drugs (AEDs) on the occurrence of focal spontaneous hippocampal paroxysmal discharges (HPD). We found that levetiracetam (600mg/kg), tiagabine (0.6mg/kg), and diazepam (2mg/kg) were effective in the MTLE mouse model, while only high doses of valproate (300mg/kg) and carbamazepine (75mg/kg) were able to suppress HPD, with strong side effects. Methods: In the present study, we further characterized the effect of these AEDs on the EEG signal, recorded in the hippocampus of the MTLE mouse, using quantitative EEG (qEEG). First, we quantified the drug-induced modifications of power in the different frequency bands during interictal periods (background EEG). Then, we assessed the spectral changes in the HPDs caused by the different drugs.Results: Among the different AEDs tested here, only with levetiracetam and valproate both the interictal and HPD power spectra remained unchanged. By contrast, the three remaining drugs all induced an increase of background EEG power, each with a specific signature (Carbamazepine: and ; Diazepam: , and ; Tiagabine: , and ). These same three drugs also altered the frequency content of hippocampal seizures during the first hour post-treatment. Diazepam decreased the powers of and , which are the bands holding the power of hippocampal spikes, and diminished fast oscillations as well ( ). Tiagabine also reduced the power, but left all the other power bands unchanged. Surprisingly, we found that carbamazepine strongly increased the power of HPDs in a wide range of frequencies ( , , and ). This suggests that once the hippocampal discharges re-appeared after treatment, they were more powerful than before treatment. For instance, the power of the 1 to 12 Hz frequency band was augmented by 31%, when compared to pre-treatment HPDs.Conclusions: Altogether these data show that each AED displays a specific EEG fingerprint on both interictal periods and HPDs in a model of MTLE in mouse. These pre-clinical data will allow a better characterization of the pharmacological effects of authorized AEDs, and will provide a solid reference for the development of new drugs.