Abstracts

Rationale: High-frequency oscillations (HFOs) in the ripple band (80-200 Hz) are found in normal limbic structures, and are associated with memory processes. Ripples along with fast-ripples (250-500 Hz) are also recorded from patients presenting with mesial temporal lobe epilepsy (MTLE) and may represent epileptogenic biomarkers. However, it is unclear whether the electrographic characteristics of physiological and pathological ripples differ before and after status epilepticus (SE). To address this issue we compared the electrophysiological characteristics of ripples recorded from limbic areas in the same animals before and after pilocarpine-induced SE. Methods: Sprague-Dawley rats (250-275 g; n=8) were implanted with bipolar depth electrodes in the CA3 region of the hippocampus and in the entorhinal cortex (EC). HFOs were recorded in the EEG of both regions during 1 week before the SE. SE was induced by treating rats with scopolamine methylnitrate (1 mg/kg i.p.) and 30 min later with a single dose of pilocarpine hydrochloride (380 mg/kg, i.p), and it was stopped after 1 hour with diazepam (5 mg/kg, s.c.) and ketamine (50 mg/kg, s.c.). Continuous recordings were performed from day 1 to day 11 after SE. Ten minute epochs of slow wave sleep were selected for each day in order to analyse the occurrence of ripples and fast ripples. The duration and frequency of ripples occurring before SE were compared to those of ripples occurring after SE. Results: We found that ripples occurred less frequently before (average rate of occurrence: 0.04 ± 0.02 events/s) compared to after SE (0.1 ± 0.03 events/s; n=8; Wilcoxon, p < 0.05). In addition, post-SE ripples occurring outside of interictal spikes, were significantly more frequent than ripples occurring on interictal spikes (0.1 ± 0.05 and 0.04 ± 0.012 events/s, respectively, Wilcoxon, p < 0.05). Fast ripples were only present after SE. Ripples occurring before and after SE had comparable duration (34 ± 1ms and 35 ± 1ms, respectively). The increase in ripple occurrence after SE was significantly correlated between CA3 and EC (linear regression analysis, p=0.004). Wavelet transform analysis also demonstrated a higher, narrower and less variable frequency-domain for ripple events recorded after SE, both in CA3 and EC, as compared to those seen before SE. Conclusions: Our findings show that the occurrence of ripple increases after SE, in CA3 and EC. Ripples before and after SE do not show significant differences in terms of duration. However, ripples after SE are less variable in frequency content compared to ripples before SE. These results suggest that in the pilocarpine model of MTLE, epileptogenesis is accompanied by specific changes in the ripple band.