Department of Neurology, University of Iowa, Iowa City, IA 52242, USA.
Department of Neurosurgery, University of Iowa, Iowa City, IA 52242, USA.
Epilepsy Behav. 2021 Aug;121(Pt B):106440. doi: 10.1016/j.yebeh.2019.07.041. Epub 2019 Aug 6.
Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in patients with refractory epilepsy. Human studies and animal models suggest that respiratory arrest is the initiating event leading to death in many cases of SUDEP. It has previously been reported that the onset of apnea can coincide with the spread of seizures to the amygdala, and apnea can be reproduced by electrical stimulation of the amygdala. The aim of the current work was to determine if the amygdala is required for seizure-induced respiratory arrest (S-IRA) in a mouse model of SUDEP. Experiments were performed on DBA/1 mice that have audiogenic seizures with a high incidence of fatal postictal respiratory arrest. Electrolytic lesions of the amygdala significantly reduced the incidence of S-IRA without altering seizures, baseline breathing, or the hypercapnic ventilatory response. These results indicate that the amygdala is a critical node in a pathway to the lower brainstem that is needed for seizures to cause respiratory arrest. SIGNIFICANCE STATEMENT: Sudden unexpected death in epilepsy is the most common cause of mortality in patients with refractory epilepsy, and S-IRA is thought to be important in the pathophysiology in many cases. In a patient with epilepsy, the onset of apnea has been shown to coincide with spread of seizures to the amygdala, and in multiple patients, apnea was induced by stimulation of the amygdala. Here, we show that lesions of the amygdala reduced the incidence of S-IRA and death in a mouse model of SUDEP. These results provide evidence that the amygdala may be a critical node in the pathway by which seizures influence the brainstem respiratory network to cause apnea. This article is part of the Special Issue NEWroscience 2018.
癫痫性猝死（SUDEP）是耐药性癫痫患者最常见的死亡原因。人体研究和动物模型表明，呼吸暂停是导致许多 SUDEP 病例死亡的起始事件。先前有报道称，呼吸暂停的发作可能与癫痫发作向杏仁核的传播同时发生，并且可以通过杏仁核的电刺激再现呼吸暂停。目前这项工作的目的是确定在 SUDEP 的小鼠模型中，杏仁核是否是癫痫发作引起的呼吸暂停（S-IRA）所必需的。在具有高致死性癫痫后呼吸暂停发生率的听觉性癫痫发作的 DBA/1 小鼠上进行了实验。杏仁核的电解损伤显著降低了 S-IRA 的发生率，而不改变癫痫发作、基础呼吸或高碳酸血症通气反应。这些结果表明，杏仁核是通往脑干的关键节点，对于癫痫发作引起呼吸暂停是必需的。意义声明：癫痫性猝死是耐药性癫痫患者死亡的最常见原因，并且 S-IRA 被认为在许多情况下对病理生理学很重要。在癫痫患者中，呼吸暂停的发作与癫痫发作向杏仁核的传播同时发生，并且在多个患者中，通过刺激杏仁核诱导了呼吸暂停。在这里，我们显示杏仁核的损伤降低了 SUDEP 小鼠模型中 S-IRA 和死亡的发生率。这些结果提供了证据，表明杏仁核可能是癫痫影响脑干呼吸网络引起呼吸暂停的途径中的关键节点。本文是《NEWroscience 2018 特刊》的一部分。
