Hrnčić Dragan, Grubač Željko, Rašić-Marković Aleksandra, Šutulović Nikola, Šušić Veselinka, Bjekić-Macut Jelica, Stanojlović Olivera
Laboratory of Neurophysiology, Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia.
Physiol Behav. 2016 Mar 1;155:188-94. doi: 10.1016/j.physbeh.2015.12.016. Epub 2015 Dec 17.
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 6h: 1) sleep disruption (sleep interrupted, SI; 30s 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.
睡眠中断是睡眠呼吸暂停的主要症状之一。阻塞性睡眠呼吸暂停在难治性癫痫患者中尤为常见，但其潜在病因远未得到解决。因此，关于这个问题的转化研究很重要。我们的目的是使用林丹诱导的难治性癫痫实验模型，研究睡眠中断对大鼠癫痫易感性的影响。通过跑步机方法（工作时皮带速度设定为0.02 m/s，停止模式时设定为0.00 m/s）对植入脑电图电极的雄性Wistar大鼠进行睡眠中断。将动物分配到持续6小时的实验条件下：1）睡眠中断（睡眠被打断，SI；每2分钟工作30秒，停止模式90秒；共180个周期）；2）活动对照（AC，工作10分钟，停止模式30分钟，共9个周期）；3）跑步机室对照（TC，仅停止模式）。之后，对动物进行腹腔注射林丹（L，4 mg/kg，SI+L、AC+L和TC+L组）或二甲基亚砜（DMSO，SIc、ACc和TCc组）。通过癫痫发作发生率、首次发作的潜伏时间及其在给药后30分钟内的严重程度来评估惊厥行为。在记录的脑电图中确定发作期的数量和持续时间。与TC+L组的动物相比，经历睡眠中断的动物（SI+L组）中，林丹诱导的癫痫发作的发生率和严重程度显著增加，潜伏时间显著缩短。与AC+L组相比，SI+L组的癫痫发作潜伏期也显著缩短。与AC+L组相比，SI+L组的发作期数量增加，其持续时间呈增加趋势。在TCc、ACc和SIc组中未观察到惊厥迹象，脑电图中也未出现发作期。这些结果表明，睡眠中断促进了林丹癫痫啮齿动物模型中癫痫活动的诱导，从而使对这一现象的转化研究成为可能。
