Time-dependent evolution of seizures in a model of mesial temporal lobe epilepsy

Charles Behr, Maxime Lévesque, Thomas Stroh, Massimo Avoli

Low-voltage fast (LVF) and hypersynchronous (HYP) - onset seizures occur in the EEG obtained with depth electrodes from mesial temporal lobe epilepsy (MTLE) patients and animal models. In epileptic rats analyzed up to approximately two weeks after pilocarpine-induced status epilepticus (SE), these patterns are associated with specific high-frequency oscillation (HFO) content: ripples (80-200Hz) or fast-ripples (250-500Hz) predominate in LVF or HYP seizures, respectively. To establish whether these features change over the course of the disease, we recorded the EEG from the hippocampal CA3 subfield, subiculum, entorhinal cortex and dentate gyrus in two groups of pilocarpine-treated rats: the "early stage group" (n=8) was analyzed from day 3 to 20 post-SE while the "late stage group" (n=7) was studied from day 27 to 53 post-SE. We found that: (i) HYP and LVF seizures prevail in the early and late stage group, respectively; (ii) HYP seizures mainly originate from CA3 in the early stage group only; (iii) LVF seizures in both early and late stage group originate from a diffuse network; (iv) LVF and HYP seizures in the early stage group are mainly associated with ripples and fast ripples, respectively; but (v) fast ripples predominate in the late stage group, regardless of seizure onset pattern. Finally, extensive neuronal loss occurred in the hippocampus of the late stage group. Our results reveal that significant changes in ictogenesis and HFO occurrence, which are associated with the manifestation of severe hippocampal damage, occur over time in this MTLE model.