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Sequence of physiological events during oxygen conserving reflex activation leading to sudden death in epilepsy

节氧反射激活期间导致癫痫猝死的生理事件序列

基本信息

批准号：
10310425
负责人：
Pedro Irazoqui
金额：
$ 40.94万
依托单位：
JOHNS HOPKINS UNIVERSITY
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：
2020-12-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10310425
关键词：
Acute Age Air Movements American Anesthesia procedures Animal Model Animals Apnea Autonomic nervous system Blood Blood Pressure Bone Screws Bradycardia Brain Brain Stem Cardiac Catheters Central Sleep Apnea Cessation of life Chronic Clinical Data Complication Coupled Data Data Set Development Disease Diving Drops Electrocardiogram Electrocorticogram Electrodes Epilepsy Event Family Female Heart Heart Arrest Heart Rate Hippocampus (Brain)Human Individual Intraperitoneal Injections Kainic Acid Larynx Lead Link Long-Evans Rats Measures Modeling Monitor Neurons Nose Organ Oxygen Pathology Pathway interactions Physiologic Monitoring Physiologic pulse Physiological Prevention Rattus Recovery Reflex action Respiratory Diaphragm Rest Role Seizures Signal Transduction Sudden Death Sudden infant death syndrome System Tetanus Time United States Work awake diving reflex fighting implantable device insight intraperitoneal male novel peripheral blood vessel prevent public health relevance relating to nervous system respiratory response subcutaneous sudden unexpected death in epilepsy vasoconstriction

项目摘要

Project Summary Sudden unexpected death in epilepsy (SUDEP) is a fatal complication of epilepsy that kills approximately 4,000 Americans every year. SUDEP is difficult to study because, while common, it usually occurs unobserved. The limited clinical data that exists suggests that SUDEP is a cardiorespiratory collapse that occurs directly after a seizure. Cardiorespiratory function is largely modulated by the autonomic nervous system (ANS). Sympathetic and parasympathetic autonomic nervous system pathways typically operate in opposition, so co- activation is rare. In the Oxygen Conserving family of Reflexes (OCRs), both pathways co-activate to induce breath-holding (apnea), lowered heart rate (bradycardia), and narrowing of peripheral blood vessels (vasoconstriction). Apnea prevents aspiration. Bradycardia conserves oxygen. Vasoconstriction prioritizes blood-carrying oxygen to essential organs (i.e. heart and brain). Seizure-induced autonomic disfunction, coupled with an externally triggered OCR may lead to death in Sudden Unexpected Death in Epilepsy (SUDEP). To elucidate the causal relationship between physiological parameters, OCRs, and sudden death, we propose to measure a physiological baseline of various oxygen conserving reflexes in healthy, anesthetized animals in Aim 1. This will establish a baseline for the temporal relationship between: cardiac, respiratory, and neural physiological signals in healthy animals before, during, and after OCR. It will also provide an important data set for subsequent exploration of causal relationships between those signals in both healthy and autonomically compromised subjects. Implications extend beyond SUDEP. In Aim 2 will then identify changes from the physiological baseline in various oxygen conserving reflexes for seizing animals. This will provide data of the specific role of various models of epilepsy, on compromising the autonomic system in the context of triggered OCR, and will show the unique sequence of events leading to sudden death in seizing animals. In Aim 3 we shift from acute to chronic animal models. We will determine the importance of awake, freely- behaving, chronic epilepsy on the physiological chain-of-events implicated in sudden death. We will do this using previously developed by us implantable devices to monitor the complete range of physiological parameters in chronic, freely-behaving male and female rats. Separating seizing and non-seizing, OCR vs no- OCR, responses in the same freely-moving animal over time will provide an entirely new window into the role of sympathetic and parasympathetic co-activation in normal and autonomic-compromised subjects.

项目总结