Sleep disruption increases seizure susceptibility: Behavioral and EEG evaluation of an experimental model of sleep apnea

• We investigated the effects of sleep disruption on seizure susceptibility of rats.
• We used experimental model of lindane-induced refractory seizures.
• Sleep disruption frequency resembled that in patients with severe sleep apnea.
• Sleep disruption potentiated both behavioral and EEG epileptic activity in rat.
• This could explain the occurrence of epileptic symptoms in sleep apnea patients.

Sleep disruption accompanies sleep apnea as one of its major symptoms. Obstructive sleep apnea is particularly common in patients with refractory epilepsy, but causing factors underlying this are far from being resolved. Therefore, translational studies regarding this issue are important. Our aim was to investigate the effects of sleep disruption on seizure susceptibility of rats using experimental model of lindane-induced refractory seizures.Sleep disruption in male Wistar rats with implanted EEG electrodes was achieved by treadmill method (belt speed set on 0.02 m/s for working and 0.00 m/s for stop mode, respectively). Animals were assigned to experimental conditions lasting 6 h: 1) sleep disruption (sleep interrupted, SI; 30 s working and 90 s stop mode every 2 min; 180 cycles in total); 2) activity control (AC, 10 min working and 30 min stop mode, 9 cycles in total); 3) treadmill chamber control (TC, only stop mode). Afterwards, the animals were intraperitoneally treated with lindane (L, 4 mg/kg, SI + L, AC + L and TC + L groups) or dimethylsulfoxide (DMSO, SIc, ACc and TCc groups). Convulsive behavior was assessed by seizure incidence, latency time to first seizure, and its severity during 30 min after drug administration. Number and duration of ictal periods were determined in recorded EEGs.Incidence and severity of lindane-induced seizures were significantly increased, latency time significantly decreased in animals undergoing sleep disruption (SI + L group) compared with the animals from TC + L. Seizure latency was also significantly decreased in SI + L compared to AC + L groups. Number of ictal periods were increased and duration of it presented tendency to increase in SI + L comparing to AC + L. No convulsive signs were observed in TCc, ACc and SIc groups, as well as no ictal periods in EEG.These results indicate sleep disruption facilitates induction of epileptic activity in rodent model of lindane-epilepsy enabling translational research of this phenomenon.