Decreased Fast Ripples in the Hippocampus of Rats with Spontaneous Recurrent Seizures Treated with Carbenoxolone and Quinine

BACKGROUND In models of temporal lobe epilepsy and in patients with this pathology, high frequency oscillations called fast ripples (FRs, 250-600 Hz) can be observed. FRs are considered potential biomarkers for epilepsy and, in the light of many in vitro and in silico studies, we thought that electrical synapses mediated by gap junctions might possibly modulate FRs in vivo. METHODS Animals with spontaneous recurrent seizures induced by pilocarpine administration were implanted with movable microelectrodes in the right anterior and posterior hippocampus to evaluate the effects of gap junction blockers administered in the entorhinal cortex. The effects of carbenoxolone (50 nmoles) and quinine (35 pmoles) on the mean number of spontaneous FR events (occurrence of FRs), as well as on the mean number of oscillation cycles per FR event and their frequency, were assessed using a specific algorithm to analyze FRs in intracranial EEG recordings. RESULTS We found that these gap junction blockers decreased the mean number of FRs and the mean number of oscillation cycles per FR event in the hippocampus, both during and at different times after carbenoxolone and quinine administration. CONCLUSION These data suggest that FRs may be modulated by gap junctions, although additional experiments in vivo will be necessary to determine the precise role of gap junctions in this pathological activity associated with epileptogenesis.