The effect of time-of-day and circadian phase on vulnerability to seizure-induced death in two mouse models.
The effect of time-of-day and circadian phase on vulnerability to seizure-induced death in two mouse models.
复制标题
在两种小鼠模型中，不同时间和昼夜节律阶段对致敏性死亡的影响。
DOI：
10.1113/jp280856
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发表时间：
2021-03
影响因子：
5.5
通讯作者：
Buchanan, Gordon F.
中科院分区：
文献类型：
--
作者：
Purnell, Benton S.;Petrucci, Alexandra N.;Li, Rui;Buchanan, Gordon F.
癫痫猝死（Sudden unexpected death in epilepsy，SUDEP）是癫痫相关死亡的主要原因。SUDEP通常发生在癫痫发作后的夜间。哺乳动物生理的许多方面都受到昼夜节律的调节，这可能使夜间发生的癫痫发作更加危险。使用两个小鼠模型的尿素诱导的死亡，我们证明，一天中的时间和昼夜节律改变脆弱性尿素诱导的死亡。我们将正常携带的DBA/1小鼠暴露于一天中不同时间的潜在癫痫诱导声刺激，并比较癫痫发作的特征和结果。一天中的时间并没有改变癫痫发作的可能性，但它确实改变了癫痫诱发死亡的可能性。为了确定昼夜节律是否改变对癫痫诱导的死亡的易感性，我们在不同的昼夜节律时间点在自由奔跑的C57 BL/6 J小鼠中诱导最大电休克癫痫发作，同时通过全身体积描记法测量呼吸。昼夜节律不影响癫痫发作的严重程度，但它确实改变了发作后呼吸结果和癫痫诱发死亡的可能性。与我们的预期相反，在夹带和自由奔跑的小鼠中，夜间和主观夜间分别最容易受到麻醉诱导死亡的影响。这些研究结果表明，昼夜节律可能是负责增加夜间SUDEP的患病率，并认为潜在的机制是夜间和昼夜哺乳动物之间的相位保守。本研究中的所有癫痫发作均在清醒期间诱发，表明时间点对癫痫诱发死亡的易感性的影响不是睡眠的结果。了解为什么SUDEP在夜间发生得更多，可以为未来的预防措施提供信息。
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death. SUDEP typically happens during the night following a seizure. Many aspects of mammalian physiology are regulated by circadian rhythms in ways that might make seizures that occur during the night more dangerous. Using two mouse models of seizure-induced death we demonstrate that time-of-day and circadian rhythms alter vulnerability to seizure-induced death. We exposed normally entrained DBA/1 mice to a potentially seizure-inducing acoustic stimulus at different times of day and compared the characteristics and outcomes of the seizures. Time-of-day did not alter the likelihood of a seizure, but it did alter the likelihood of seizure-induced death. To determine whether circadian rhythms alter vulnerability to seizure-induced death we induced maximal electroshock seizures in free-running C57BL/6J mice at different circadian time points while measuring breathing via whole body plethysmography. Circadian phase did not affect seizure severity, but it did alter postictal respiratory outcomes and the likelihood of seizure-induced death. Contrary to our expectations, in entrained and free-running mice, vulnerability to seizure-induced death was greatest during the night and subjective night, respectively. These findings suggest that circadian rhythmicity may be responsible for the increased nighttime prevalence of SUDEP and that the underlying mechanism is phase conserved between nocturnal and diurnal mammals. All seizures in this investigation were induced during wakefulness indicating that the effect of time point on vulnerability to seizure-induced death was not the result of sleep. Understanding why SUDEP happens more during the night may inform future preventative countermeasures.