Department of Physiological Sciences, Institute of Biological Sciences, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
Department of Physiology and Biophysics, Institute of Biomedical Science, Universidade de São Paulo, São Paulo, Brazil.
Epilepsy Behav. 2024 Aug;157:109848. doi: 10.1016/j.yebeh.2024.109848. Epub 2024 May 31.
OSA is known to increase the risk for SUDEP in persons with epilepsy, but the relationship between these two factors is not clear. Also, there is no study showing the acute responses to obstructive apnea in a chronic epilepsy model. Therefore, this study aimed to characterize cardiorespiratory responses to obstructive apnea and chemoreceptor stimulation in rats. In addition, we analyzed respiratory centers in the brain stem by immunohistochemistry. Epilepsy was induced with pilocarpine. About 30-60 days after the first spontaneous seizure, tracheal and thoracic balloons, and electrodes for recording the electroencephalogram, electromyogram, and electrocardiogram were implanted. Intermittent apneas were made by inflation of the tracheal balloon during wakefulness, NREM sleep, and REM sleep. During apnea, respiratory effort increased, and heart rate fell, especially with apneas made during wakefulness, both in control rats and rats with epilepsy. Latency to awake from apnea was longer with apneas made during REM than NREM, but rats with epilepsy awoke more rapidly than controls with apneas made during REM sleep. Rats with epilepsy also had less REM sleep. Cardiorespiratory responses to stimulation of carotid chemoreceptors with cyanide were similar in rats with epilepsy and controls. Immunohistochemical analysis of Phox2b, tryptophan hydroxylase, and NK1 in brain stem nuclei involved in breathing and sleep (retrotrapezoid nucleus, pre-Bötzinger complex, Bötzinger complex, and caudal raphe nuclei) revealed no differences between control rats and rats with epilepsy. In conclusion, our study showed that rats with epilepsy had a decrease in the latency to awaken from apneas during REM sleep, which may be related to neuroplasticity in some other brain regions related to respiratory control, awakening mechanisms, and autonomic modulation.
阻塞性睡眠呼吸暂停（OSA）已知会增加癫痫患者发生 SUDEP 的风险，但这两个因素之间的关系尚不清楚。此外，目前尚无研究显示慢性癫痫模型中对阻塞性呼吸暂停的急性反应。因此，本研究旨在描述阻塞性呼吸暂停和化学感受器刺激对大鼠的心肺反应。此外，我们通过免疫组织化学分析了脑干呼吸中枢。采用匹鲁卡品诱导癫痫。首次自发性癫痫发作后约 30-60 天，植入气管和胸气球以及用于记录脑电图、肌电图和心电图的电极。在觉醒、非快速眼动（NREM）睡眠和快速眼动（REM）睡眠期间，通过充气气管气球来进行间歇性呼吸暂停。在呼吸暂停期间，呼吸努力增加，心率下降，尤其是在觉醒时进行呼吸暂停时，在对照大鼠和癫痫大鼠中均如此。与 NREM 相比，REM 睡眠期间的呼吸暂停唤醒潜伏期更长，但 REM 睡眠期间的癫痫大鼠比对照大鼠更快地醒来。癫痫大鼠的 REM 睡眠也较少。用氰化物刺激颈动脉化学感受器引起的心肺反应在癫痫大鼠和对照组大鼠中相似。对脑干呼吸和睡眠相关核（梯形核、前 Bötzinger 复合体、Bötzinger 复合体和尾状核）中涉及的 Phox2b、色氨酸羟化酶和 NK1 的免疫组织化学分析显示，对照组大鼠和癫痫大鼠之间没有差异。总之，我们的研究表明，癫痫大鼠在 REM 睡眠期间从呼吸暂停中醒来的潜伏期缩短，这可能与呼吸控制、觉醒机制和自主调节相关的某些其他脑区的神经可塑性有关。
