Mechanisms of SUDEP: Failure to Autoresuscitate

SUDEP 的机制:自动复苏失败

基本信息

  • 批准号:
    9978389
  • 负责人:
  • 金额:
    $ 40.01万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-04-01 至 2022-09-30
  • 项目状态:
    已结题

项目摘要

Project Summary Epilepsy is the third most common chronic neurological disorder, affecting about 3 million persons in the USA. Approximately 30% of patients remain refractory to medical treatment. Sudden unexpected death in epilepsy (SUDEP) occurs in at least 1:1000 people with epilepsy annually. This risk increases to ~1:150 per year for individuals with poorly controlled and severe seizures, and these risk statistics are thought to be underestimated. In terms of person years lost, SUDEP is second only to stroke. Although some risk factors have been elucidated, the unpredictability of SUDEP has contributed to major challenges in human studies. Thus, it is unknow whether systems necessary to promote survival deteriorate and permit SUDEP. The goal of this proposal addresses this critical need. We propose the innovative idea that susceptibility to SUDEP is progressive. We aim to identify whether systems necessary for survival become unstable prior to death, and thus permit death. Understanding how survival systems fail will identify targets for treatment strategies to postpone or prevent SUDEP. We capitalize on our published and novel findings regarding the molecular and physiological changes that precede SUDEP and contribute to susceptibility. Here, using a preclinical mouse model of SUDEP, combined whole body plethysmography and EEG-EMG-ECG recording techniques and ex vivo slice electrophysiology, we will employ innovative approaches and analytical methods to determine whether progressive impairment of survival responses precede SUDEP. In this application, we continue the journey to highly novel and translatable solutions to a major human health problem.
项目摘要 癫痫是第三常见的慢性神经系统疾病,在美国影响约300万人。 大约30%的患者仍然对药物治疗无效。癫痫猝死 (SUDEP)每年至少发生在1:1000的癫痫患者中。这种风险增加到每年约1:150, 这些风险统计数据被认为被低估了。 就人年损失而言,SUDEP仅次于中风。虽然已经阐明了一些风险因素, SUDEP的不可预测性导致了人类研究中的重大挑战。不知道是不是。 促进生存所必需的系统恶化并允许SUDEP。本提案的目标是解决这一问题 关键的需要。我们提出了SUDEP易感性是渐进性的创新观点。我们的目标是找出 生存所必需的系统是否在死亡之前变得不稳定,从而允许死亡。理解 如何生存系统失败将确定治疗策略的目标,以推迟或预防SUDEP。我们 利用我们已发表的和新的发现,关于分子和生理变化, SUDEP并导致易感性。在这里,使用SUDEP的临床前小鼠模型, 体积描记和EEG-EMG-ECG记录技术和离体切片电生理学,我们将采用 创新的方法和分析方法,以确定是否进行性损害的生存 响应先于SUDEP。在这个应用程序中,我们继续旅程,以高度新颖和可翻译的解决方案 一个重大的人类健康问题。

项目成果

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Kristina A Simeone其他文献

Kristina A Simeone的其他文献

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{{ truncateString('Kristina A Simeone', 18)}}的其他基金

Autoresuscitation and SUDEP
自动复苏和 SUDEP
  • 批准号:
    10598136
  • 财政年份:
    2022
  • 资助金额:
    $ 40.01万
  • 项目类别:
Adenosine, Hypocretin and Sleep Disorder Comorbidities Associated with Epilepsy
腺苷、下丘脑分泌素和与癫痫相关的睡眠障碍合并症
  • 批准号:
    8297937
  • 财政年份:
    2012
  • 资助金额:
    $ 40.01万
  • 项目类别:
Adenosine, Hypocretin and Sleep Disorder Comorbidities Associated with Epilepsy
腺苷、下丘脑分泌素和与癫痫相关的睡眠障碍合并症
  • 批准号:
    8412772
  • 财政年份:
    2012
  • 资助金额:
    $ 40.01万
  • 项目类别:
Adenosine, Hypocretin and Sleep Disorder Comorbidities Associated with Epilepsy
腺苷、下丘脑分泌素和与癫痫相关的睡眠障碍合并症
  • 批准号:
    8601911
  • 财政年份:
    2012
  • 资助金额:
    $ 40.01万
  • 项目类别:
Adenosine, Hypocretin and Sleep Disorder Comorbidities Associated with Epilepsy
腺苷、下丘脑分泌素和与癫痫相关的睡眠障碍合并症
  • 批准号:
    8997122
  • 财政年份:
    2012
  • 资助金额:
    $ 40.01万
  • 项目类别:

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