Laboratory of Neurophysiology , Institute of Medical Physiology "Richard Burian" , Belgrade University Faculty of Medicine , Belgrade , Serbia.
Institute of Clinical and Medical Biochemistry , Belgrade University Faculty of Medicine , Belgrade , Serbia.
Acta Neurobiol Exp (Wars). 2021;81(1):96-109. doi: 10.21307/ane-2021-010.
Brain hyperexcitability in sleep apnea is believed to be provoked by hypoxemia, but sleep fragmentation can also play a significant role. Sleep fragmentation can trigger inflammatory mechanisms. The aim of this research was to investigate the effects of chronic sleep fragmentation on seizure susceptibility and brain cytokine profile. Chronic sleep fragmentation in male rats with implanted EEG electrodes was achieved by the treadmill method. Rats were randomized to: treadmill control (TC); activity control (AC) and sleep fragmentation (SF) group. Convulsive behavior was assessed 14 days later by seizure incidence, latency time and seizure severity during 30 min following lindane administration. The number and duration of EEG ictal periods were determined. Levels of IL-1β and IL-6 were measured in the animals' serum and brain structures (hippocampus, thalamus and cerebral cortex), in separate rat cohort that underwent the same fragmentation protocol except lindane administration. Incidence and severity of seizures were significantly increased, while latency was significantly decreased in SF+L compared with TC+L group. Seizure latency was also significantly decreased in SF+L compared to AC+L group. The number and duration of ictal periods were increased in the SF+L compared to the AC+L group. IL-1β was significantly increased in the thalamus, cortex and hippocampus in the SF compared to the AC and TC groups. IL-6 was statistically higher only in the cortex of SF animals, while in the thalamic or hippocampal tissue, no difference was observed between the groups. It could be concluded that fourteen-day sleep fragmentation increases seizure susceptibility in rats and modulates brain production of IL-1β and IL-6. Brain hyperexcitability in sleep apnea is believed to be provoked by hypoxemia, but sleep fragmentation can also play a significant role. Sleep fragmentation can trigger inflammatory mechanisms. The aim of this research was to investigate the effects of chronic sleep fragmentation on seizure susceptibility and brain cytokine profile. Chronic sleep fragmentation in male rats with implanted EEG electrodes was achieved by the treadmill method. Rats were randomized to: treadmill control (TC); activity control (AC) and sleep fragmentation (SF) group. Convulsive behavior was assessed 14 days later by seizure incidence, latency time and seizure severity during 30 min following lindane administration. The number and duration of EEG ictal periods were determined. Levels of IL-1β and IL-6 were measured in the animals’ serum and brain structures (hippocampus, thalamus and cerebral cortex), in separate rat cohort that underwent the same fragmentation protocol except lindane administration. Incidence and severity of seizures were significantly increased, while latency was significantly decreased in SF+L compared with TC+L group. Seizure latency was also significantly decreased in SF+L compared to AC+L group. The number and duration of ictal periods were increased in the SF+L compared to the AC+L group. IL-1β was significantly increased in the thalamus, cortex and hippocampus in the SF compared to the AC and TC groups. IL-6 was statistically higher only in the cortex of SF animals, while in the thalamic or hippocampal tissue, no difference was observed between the groups. It could be concluded that fourteen-day sleep fragmentation increases seizure susceptibility in rats and modulates brain production of IL-1β and IL-6.
睡眠呼吸暂停中的大脑过度兴奋被认为是由低氧血症引起的，但睡眠片段化也可能起重要作用。睡眠片段化可以触发炎症机制。本研究旨在探讨慢性睡眠片段化对癫痫易感性和大脑细胞因子谱的影响。通过跑步机方法实现植入 EEG 电极的雄性大鼠的慢性睡眠片段化。大鼠被随机分为：跑步机对照（TC）；活动对照（AC）和睡眠片段化（SF）组。14 天后，通过 lindane 给药后 30 分钟内癫痫发作的发生率、潜伏期和严重程度评估癫痫发作的易感性。记录 EEG 发作期的数量和持续时间。在接受相同片段化方案但不给予 lindane 的单独大鼠队列中，测量了血清和脑结构（海马体、丘脑和大脑皮层）中 IL-1β 和 IL-6 的水平。与 TC+L 组相比，SF+L 组的癫痫发作发生率和严重程度显著增加，而潜伏期显著缩短。与 AC+L 组相比，SF+L 组的癫痫发作潜伏期也明显缩短。与 AC+L 组相比，SF+L 组的发作期数量和持续时间增加。与 AC 和 TC 组相比，SF 组的丘脑、皮层和海马体中的 IL-1β 显著增加。仅在 SF 动物的皮层中，IL-6 统计学上更高，而在丘脑或海马组织中，各组之间没有差异。可以得出结论，14 天的睡眠片段化增加了大鼠的癫痫易感性，并调节了大脑中 IL-1β 和 IL-6 的产生。
