Departments of Physiology & Pharmacology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY, USA; Otolaryngology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
Neurobiol Dis. 2019 Apr;124:408-415. doi: 10.1016/j.nbd.2018.12.019. Epub 2018 Dec 25.
The spread of epileptic seizure activity to brainstem respiratory and autonomic regions can elicit episodes of obstructive apnea and of central apnea with significant oxygen desaturation and bradycardia. Previously, we argued that central apneic events were not consequences of respiratory or autonomic activity failure, but rather an active brainstem behavior equivalent to the diving response resulting from seizure spread. To test the similarities of spontaneous seizure-associated central apneic episodes to evoked diving responses, we used nasopharyngeal irrigation with either cold water or mist for 10 or 60 s to elicit the diving response in urethane-anesthetized animals with or without kainic acid-induced seizure activity. Diving responses included larger cardiovascular changes during mist stimuli than during water stimuli. Apneic responses lasted longer than 10 s in response to 10 s stimuli or about 40 s in response to 60 s stimuli, and outlasted bradycardia. Repeated 10 s mist applications led to an uncoupling of the apneic episodes (which always occurred) from the bradycardia (which became less pronounced with repetition). These uncoupled events matched the features of observed spontaneous seizure-associated central apneic episodes. The duration of spontaneous central apneic episodes correlated with their frequency, i.e. longer events occurred when there were more events. Based on our ability to replicate the properties of seizure-associated central apneic events with evoked diving responses during seizure activity, we conclude that seizure-associated central apnea and the diving response share a common neural basis and may reflect an attempt by brainstem networks to protect core physiology during seizure activity.
癫痫发作活动向脑干呼吸和自主区域的扩散可引发阻塞性呼吸暂停和中枢性呼吸暂停发作,伴有显著的氧饱和度下降和心动过缓。此前,我们认为中枢性呼吸暂停事件不是呼吸或自主活动失败的后果,而是源自癫痫扩散的一种活跃的脑干行为,相当于潜水反应。为了测试自发性癫痫相关中枢性呼吸暂停发作与诱发潜水反应的相似性,我们使用鼻咽冲洗,用冷水或雾气刺激 10 秒或 60 秒,以诱发有无海人酸诱导癫痫发作的氨基甲酸乙酯麻醉动物的潜水反应。潜水反应中,雾气刺激比水刺激引起更大的心血管变化。在 10 秒刺激时,呼吸暂停反应持续时间超过 10 秒,在 60 秒刺激时持续约 40 秒,且持续时间长于心动过缓。重复 10 秒的雾气刺激导致呼吸暂停事件(总是发生)与心动过缓(随着重复刺激变得不那么明显)脱钩。这些脱钩事件与观察到的自发性癫痫相关中枢性呼吸暂停发作的特征相匹配。自发性中枢性呼吸暂停发作的持续时间与其频率相关,即发生的事件越多,持续时间越长。基于我们在癫痫发作期间用诱发潜水反应复制与癫痫相关的中枢性呼吸暂停发作的特性的能力,我们得出结论,与癫痫相关的中枢性呼吸暂停和潜水反应具有共同的神经基础,可能反映了脑干网络在癫痫发作期间试图保护核心生理学的尝试。