Seizure-Induced Laryngospams in Mice

摘要 癫痫猝死(SUDEP)占癫痫患者死亡的17%。这些 不明原因的死亡可能是由于喉部痉挛，喉部入口的紧密关闭导致的 呼吸道阻塞。癫痫发作会引起广泛的呼吸变化，喉痉挛一直是 对发作性呼吸窘迫患者进行观察。此外，使用麻醉大鼠的模型治疗 使用氨基甲酸乙酯和海人酸，我们最近证明了癫痫诱导的喉痉挛启动了一种 阻塞性呼吸暂停、动脉血氧减饱和、心动过缓、呼吸骤停 干预，死亡。在这里，我们建议检验这样一种假设，即喉痉挛是引起 在SUDEP病例中，使用容易死亡的清醒的、未麻醉的小鼠的模型 听源性癫痫。我们的研究人群将包括两组定制的T形小鼠 气管内植入导管，同时保留喉返神经功能。在实验中 组，导管的经皮侧臂将保持开放，以提供替代气道；在对照组 组中，侧臂将关闭，以限制气流进入正常呼吸道。我们预测实验中的 小鼠将在听源性癫痫发作中幸存下来，因为替代的呼吸道将允许空气绕过喉部痉挛； 相比之下，对照组小鼠将死于癫痫发作。这项研究的结果将提供额外的 发作性喉痉挛导致死亡的证据。特别是，这种动物模型更贴近 由于缺乏麻醉剂和致痫药物，与典型患者相似。此外，这一点 这项研究直接应用于癫痫发作期间熟练的上呼吸道管理的临床领域 可能是防止病人死亡的关键因素。最后，本文的研究成果将对未来的发展起到一定的指导作用 可转化为有猝死风险的患者的复苏和预防策略 癫痫。

Abstract Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17% of deaths in epileptic patients. These unexplained deaths may be precipitated by laryngospasm, tight closure of the laryngeal inlet that causes airway obstruction. Seizures cause a wide range of respiratory changes, and laryngospasm has been observed in patients with ictal respiratory distress. Moreover, using a model of anesthetized rats treated with urethane and kainate, we recently demonstrated that seizure-induced laryngospasm initiates a sequence of obstructive apnea, arterial oxygen desaturation, bradycardia, respiratory arrest, and, without intervention, death. Here, we propose to test the hypothesis that laryngospasm is the proximal cause of death in SUDEP cases by using a model of AWAKE, UNANESTHETIZED mice that are prone to dying from audiogenic seizures. Our study population will comprise two cohorts of mice with custom-made T-shaped tubes implanted in the trachea while preserving recurrent-laryngeal-nerve function. In the experimental group, the tube's percutaneous side arm will be left open to provide an alternative airway; in the control group, the side arm will be closed to limit airflow to the normal airway. We predict that the experimental mice will survive audiogenic seizures because the alternative airway will allow air to bypass laryngospasm; the control mice, in contrast, will die from the seizures. The results of this study will provide additional evidence for the contribution of ictal laryngospasm to death. In particular, this animal model more closely resembles typical patients because of the absence of anesthetic and epileptogenic drugs. In addition, this study has direct application to the clinical arena in which skilled upper-airway management during seizures may be a key component to preventing patient deaths. Finally, the results will guide the development of resuscitative and preventative strategies that can be translated to patients at risk for sudden death in epilepsy.