Seizure-Induced Laryngospams in Mice

小鼠癫痫发作引起的喉痉挛

• 批准号: 9598204
• 负责人: MARK G STEWART
• 金额: $ 8.08万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9598204
• 关键词: Air; Anesthetics; Animal Model; Animals; Apnea; Asphyxia; Attention; Behavioral Model; Bradycardia; Breathing; Bypass; Cardiopulmonary; Cause of Death; Cessation of life; Clinical; Control Groups; Custom; Development; Electrocardiogram; Electrophysiology (science); Ensure; Epilepsy; Event; Functional disorder; Human; Implant; Implantation procedure; Intervention; Laryngismus; Laryngoscopy; Larynx; Lead; Left; Life; Link; Modeling; Mus; Nature; Operative Surgical Procedures; Oxygen; Patients; Pharmaceutical Preparations; Postoperative Period; Prevention strategy; Procedures; Pulse Oximetry; Rattus; Recurrent Laryngeal Nerve; Reproducibility; Research; Respiratory distress; Resuscitation; Risk; Role; Route; Savings; Seizures; Side; Spasm; Steel; Sudden Death; Testing; Trachea; Tracheostomy procedure; Tracheotomy procedure; Translating; Tube; Urethane; airway obstruction; arm; audiogenic seizure; awake; base; cohort; design; direct application; experimental group; experimental study; in vivo; kainate; mortality; prevent; respiratory; study population; success; sudden unexpected death in epilepsy; vocal cord

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.

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喉痉挛，喉入口关闭不严， 气道阻塞癫痫发作引起广泛的呼吸变化，喉痉挛一直是 在发作性呼吸窘迫患者中观察到。此外，使用麻醉大鼠模型， 我们最近用氨基甲酸乙酯和红藻氨酸盐证明了尿道炎引起的喉痉挛会引发一种 阻塞性呼吸暂停、动脉血氧饱和度下降、心动过缓、呼吸骤停的顺序，以及，无 干预死亡在这里，我们建议测试的假设，喉痉挛是近端的原因， 通过使用清醒、未麻醉小鼠模型观察SUDEP病例中的死亡， 听源性癫痫我们的研究群体将包括两组具有定制的T形细胞的小鼠。 在保留喉返神经功能的同时，将导管植入气管。实验 组，导管的经皮侧臂将保持开放，以提供替代气道;在对照组中， 组，侧臂将被关闭，以限制气流进入正常气道。我们预测， 小鼠将在听源性癫痫发作中存活，因为替代气道将允许空气绕过喉痉挛; 相反，对照组小鼠会死于癫痫发作。这项研究的结果将提供更多的 发作性喉痉挛导致死亡的证据。特别是，这种动物模型更接近于 由于没有麻醉剂和致癫痫药物，与典型患者相似。另外这款 这项研究直接应用于临床竞技场，其中癫痫发作期间熟练的上气道管理 可能是防止病人死亡的关键因素。最后，研究结果将指导 复苏和预防策略，可以转化为患者在猝死的风险， 癫痫