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.

中文翻译：

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杏仁核病变减少了 DBA/1 小鼠癫痫发作引起的呼吸停止

癫痫猝死 (SUDEP) 是难治性癫痫患者最常见的死亡原因。人体研究和动物模型表明，在许多 SUDEP 病例中，呼吸停止是导致死亡的起始事件。之前有报道称，呼吸暂停的发作可能与癫痫发作扩散到杏仁核同时发生，并且可以通过对杏仁核进行电刺激来重现呼吸暂停。当前工作的目的是确定在 SUDEP 小鼠模型中是否需要杏仁核来引起癫痫发作引起的呼吸停止 (S-IRA)。实验是在 DBA/1 小鼠上进行的，这些小鼠有听力性癫痫发作，致命性发作后呼吸骤停的发生率很高。杏仁核的电解损伤显着降低了 S-IRA 的发生率，而不会改变癫痫发作、基线呼吸、或高碳酸血症通气反应。这些结果表明，杏仁核是通往下脑干通路的关键节​​点，癫痫发作导致呼吸停止所需的通路。意义声明：癫痫中的突然意外死亡是难治性癫痫患者死亡的最常见原因，S-IRA 在许多情况下被认为在病理生理学中很重要。在一名癫痫患者中，呼吸暂停的发生与癫痫扩散到杏仁核同时发生，并且在多位患者中，呼吸暂停是由杏仁核的刺激引起的。在这里，我们表明杏仁核的病变降低了 SUDEP 小鼠模型中 S-IRA 的发生率和死亡。这些结果提供证据表明杏仁核可能是癫痫发作影响脑干呼吸网络导致呼吸暂停的途径中的一个关键节点。本文是特刊 NEWroscience 2018 的一部分。