Sleep state-dependent mechanisms of seizure-induced death

癫痫引起的死亡的睡眠状态依赖性机制

基本信息

批准号：
10118793
负责人：
Gordon Frank Buchanan
金额：
$ 38.2万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10118793
关键词：
Acidosis Amygdaloid structure Animal Model Arousal Biological Markers Breathing Carbon Dioxide Cardiac Cause of Death Cell Nucleus Cessation of life Clinic Data Dependence Development Disease Dorsal Electroencephalography Epilepsy Functional disorder Future Generalized seizures Genetic Goals Hippocampus (Brain)Human Impairment Individual Intervention Intractable Epilepsy Knowledge Lead Life Mediating Microdialysis Mus Neurons Neurotransmitters Pathway interactions Patients Persons Pharmacology Physiological Prevention strategy Property Publishing REM Sleep Refractory Regulation Respiratory physiology Resuscitation Risk Risk Factors Seizures Serotonergic System Serotonin Serotonin Agonists Signal Transduction Sleep Societies Supervision Testing Transgenic Organisms Wakefulness Work combat expectation hypocretin novel optogenetics prevent prophylactic respiratory response societal costs sudden unexpected death in epilepsy

项目摘要

ABSTRACT Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. The majority of SUDEP cases occur at night, during sleep, but why this is the case in unclear. It has been proposed that a portion of these cases may be due to lack of adequate supervision during the nighttime and relayed resuscitation efforts following a seizure. Recent evidence suggests this is not the whole story. There are a number of physiologic changes that occur during sleep, that may make sleep relatively intolerant to the additonal physiologic insult of a seizure. Seizure-induced impairment of respiratory, cardiac, and arousal mechanisms have all been implicated in SUDEP. All of these are subject to sleep state-dependent regulation. A large body of evidence suggests that abnormalities in signaling of the neurotransmitter serotonin are important in SUDEP. Serotonin is also regulated in a sleep state-dependent manner, and is involved in the regulation of breathing, cardiac activity, and sleep and wakefulness, and can modulate seizures. The primary goal of this proposal is to understand how seizures that occur during sleep become fatal. In pursuing this goal we will test the overarching hypothesis that serotonin is involved in regulating the state-dependence of seizure-induced death. In Aim 1 we will determine how seizures that occur during sleep dysregulate respiratory function. In Aim 2 we will determine how seizures that occur during sleep dysregulate arousal mechanisms. Finally, in Aim 3 we will determine how REM sleep is protective against seizures. Completion of these aims will provide an understanding of how seizures that occur during sleep could be fatal, and some of the findings could be directly translatable to the clinic to aid in identification of persons at risk for SUDEP and in implemention of novel prophylactic strategies. This work will additionally lay the groundwork for future projects delving deeper into these mechanisms.

抽象的癫痫（SUDEP）突然意外死亡是患者死亡的主要原因难治性癫痫。大多数SUDEP案件发生在晚上，睡眠期间，但这是为什么案件不清楚。有人提出，其中一部分可能是由于缺乏足够的夜间的监督，并在癫痫发作后转移了复苏工作。最近的证据表明这不是整个故事。有许多生理变化在睡眠期间发生，这可能会使睡眠相对不宽容，对发作。癫痫发作引起的呼吸，心脏和唤醒机制的损害均已与Sudep有关。所有这些都受到睡眠状态依赖性调节。一大堆有证据表明，神经递质5-羟色胺信号传导异常在 Sudep。 5-羟色胺也以睡眠状态依赖性调节，并参与调节呼吸，心脏活动，睡眠和清醒，并可以调节癫痫发作。该提议的主要目标是了解睡眠期间发生的癫痫发作致命的。在追求这一目标时，我们将检验5-羟色胺参与的总体假设调节癫痫发作的死亡的状态依赖性。在目标1中，我们将确定癫痫发作方式在睡眠期间发生的呼吸功能失调。在AIM 2中，我们将确定癫痫发作在睡眠失调期间发生的唤醒机制。最后，在目标3中，我们将确定如何 REM睡眠可以防止癫痫发作。这些目标的完成将提供理解在睡眠期间发生的癫痫发作可能是致命的，其中一些发现可能是直接的可翻译到诊所，以帮助确定有SUDEP风险的人并实施新颖的预防策略。这项工作还将为未来的项目奠定基础深入研究这些机制。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Time-of-day influences on respiratory sequelae following maximal electroshock-induced seizures in mice.

一天中的时间对小鼠最大电击诱发癫痫发作后呼吸系统后遗症的影响。

DOI：
10.1152/jn.00039.2017
发表时间：
2017
期刊：
Journal of neurophysiology
影响因子：
2.5
作者：
Purnell,BentonS;Hajek,MichaelA;Buchanan,GordonF
通讯作者：
Buchanan,GordonF

Selective Serotonin Reuptake Inhibitors and 5-HT2 Receptor Agonists Have Distinct, Sleep-state Dependent Effects on Postictal Breathing in Amygdala Kindled Mice.

选择性血清素再摄取抑制剂和 5-HT2 受体激动剂对杏仁核点燃小鼠的发作后呼吸具有明显的睡眠状态依赖性影响。

DOI：
10.1016/j.neuroscience.2023.01.016
发表时间：
2023
期刊：
Neuroscience
影响因子：
3.3
作者：
Joyal,KatelynG;Petrucci,AlexandraN;Littlepage-Saunders,MydirahV;Boodhoo,NicoleA;Wendt,LinderH;Buchanan,GordonF
通讯作者：
Buchanan,GordonF

Epilepsy: A dietary supplement for SUDEP prevention?

癫痫：预防 SUDEP 的膳食补充剂？

DOI：
10.1038/nrneurol.2016.114
发表时间：
2016
期刊：
Nature reviews. Neurology
影响因子：
0
作者：
Buchanan,GordonF;Richerson,GeorgeB
通讯作者：
Richerson,GeorgeB

A companion to the preclinical common data elements for physiologic data in rodent epilepsy models. A report of the TASK3 Physiology Working Group of the ILAE/AES Joint Translational Task Force.

啮齿动物癫痫模型中生理数据的临床前通用数据元素的伴随。

DOI：
10.1002/epi4.12261
发表时间：
2018
期刊：
Epilepsia open
影响因子：
3
作者：
Gorter,JanA;vanVliet,ErwinA;Dedeurwaerdere,Stefanie;Buchanan,GordonF;Friedman,Daniel;Borges,Karin;Grabenstatter,Heidi;Lukasiuk,Katarzyna;Scharfman,HelenE;Nehlig,Astrid
通讯作者：
Nehlig,Astrid

Post-ictal Generalized EEG Suppression is reduced by Enhancing Dorsal Raphe Serotonergic Neurotransmission.