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.

抽象的 癫痫（SUDEP）突然出乎意料的死亡占癫痫患者死亡的17％。这些 无法解释的死亡可能会因喉痉挛，喉部的紧密闭合而导致导致喉部的紧密闭合 气道阻塞。癫痫发作会引起广泛的呼吸道变化，喉部一直是 在发作性呼吸窘迫的患者中观察到。此外，使用治疗的麻醉大鼠模型 借助聚氨酯和海藻酸盐，我们最近证明了癫痫发作诱导的喉部启动A 阻塞性呼吸暂停，动脉氧饱和度，心动过缓，呼吸停滞的序列，没有 干预，死亡。在这里，我们建议检验以下假设，即喉部是 在SUDEP案件中使用清醒的，未经麻醉的小鼠的死亡，这些模型容易死亡 听力癫痫发作。我们的研究人群将组成两只与定制T形的小鼠 在保留复发性肺内膜功能的同时，植入气管中的管。在实验中 小组，管的经皮侧臂将被打开以提供替代气道。在控件中 小组，侧臂将被关闭，以将气流限制在普通气道上。我们预测实验 小鼠将在听觉性癫痫发作中幸存下来，因为替代气道将使空气绕过喉部。 相比之下，控制小鼠将死于癫痫发作。这项研究的结果将提供额外的 发作性喉痉挛对死亡的贡献的证据。特别是这个动物模型更接近 由于没有麻醉和癫痫药物，类似于典型的患者。此外，这 研究直接应用于临床领域 可能是预防患者死亡的关键组成部分。最后，结果将指导开发 复苏性和预防策略，可以转化为有可能突然死亡的患者 癫痫。