Comprehensive Structural and Functional Mapping of the Mammalian Cardiac Nervous System

哺乳动物心脏神经系统的全面结构和功能图谱

基本信息

批准号：
10202966
负责人：
IGOR R EFIMOV
金额：
$ 248.64万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
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：
2016-09-24 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10202966
关键词：
Ablation Anatomic Models Anatomy Animal Model Animals Area Arrhythmia Autonomic nervous system Behavior Binding Botulinum Toxins Brain Stem Cardiac Cardiac Electrophysiologic Techniques Cardiovascular Diseases Carotid Body Cells Cervical Cessation of life Chest Clinical Communities Data Decentralization Destinations Disease Efferent Neurons Electrophysiology (science)Epidural Anesthesia Functional disorder Ganglia Goals Heart Heart Abnormalities Heart Diseases Heart failure Hospitalization Human Hypertension In Vitro Injections Intervention Knowledge Life Link Maps Mechanics Mediastinal Methods Molecular Morbidity - disease rate Muscle Cells Myocardial Nerve Nerve Fibers Nervous system structure Neuraxis Neurons Neurostimulation procedures of spinal cord tissue Neurotransmitters Nodose Ganglion Organ Pathway interactions Patients Pharmacology Physiological Physiology Play Precision therapeutics Proteomics Quality of life Research Role Sensory Sensory Ganglia Spinal Cord Spinal Ganglia Structure Sympathectomy Sympathetic Ganglia Synapses Techniques Therapeutic Therapeutic Intervention Time Tissues United States Veins Viral Work afferent nerve data sharing heart disease prevention heart function heart innervation heart rhythm human disease improved in vivo indexing innovation interdisciplinary approach man mortality neurochemistry neuroregulation novel prevent relating to nervous system research study side effect sudden cardiac death targeted treatment therapeutic target therapy development tool transcriptome sequencing vagus nerve stimulation

项目摘要

Cardiovascular diseases such as heart failure, arrhythmias, and hypertension are leading causes of morbidity and mortality in the United States and world-wide. The autonomic nervous system plays a critical role in the pathophysiology of these diseases and neuraxial modulation provides an important avenue for therapeutic intervention. The major goal of our research team is to precisely define the cardiac neural hierarchy and develop circuit diagrams from the macroscopic to cellular and molecular levels and share these data on an ongoing basis with the scientific community. This effort will also provide verified methods and tools for assessing neuromodulation. The research team will make them freely available to the scientific community. A multiscale, multidisciplinary approach across various species, highly relevant to human disease, will be used to define the anatomy of cardiac innervation in high definition. Neural structure will be linked to cardiac function. The complexity of cardiac neural control necessitates an integrative approach that will represent a tour de force in this field. State-of-the-art anatomical, physiological, and pharmacological approaches from ‘cells to man’ must be combined in order to achieve the above goals. This approach will be utilized at each level of the neuraxis (heart, extracardiac intrathoracic neural structures and extrathoracic neural structures). The techniques proposed will allow, for the first time, a detailed description of the anatomical and molecular interactions at the synaptic and cell body levels in cardiac and extracardiac ganglia. The techniques used and the integration of these pathways represents the most innovative attempt to understand cardiac neural control ever undertaken. Understanding these pathways has the potential to accelerate development of therapies that will be able to precisely target neural structures and also guide methods to re-purpose already available therapies (e.g. nerve stimulators) for therapeutic purposes. Ultimately, these approaches are required to develop novel, effective, and affordable interventions for the management and prevention of heart disease and sudden cardiac death.

心力衰竭，心律不齐和高血压等心血管疾病是发病率的主要原因和在美国和全球的死亡率。自主神经系统在这些疾病和神经氧化调节的病理生理学为治疗提供了重要的途径干涉。我们研究团队的主要目标是精确定义心脏神经层次结构和开发从宏观到细胞和分子水平的电路图，并在与科学界的持续基础。这项工作还将为验证的方法和工具提供评估神经调节。研究团队将使科学界自由使用。一个多种物种的多阶立，多学科方法，与人类疾病高度相关，将用于定义高清晰度中心脏神经的解剖结构。神经结构将与心脏功能有关。心脏神经控制的复杂性必要的一种综合方法，代表巡回赛的力量在这个领域。从“细胞到人”的最新解剖学，物理和药物方法必须合并以实现上述目标。这种方法将在每个级别的每个级别中使用神经（心脏，心外胸腔神经结构和牙外神经结构）。提出的技术将首次允许解剖学和分子的详细描述心脏和心外神经节突触和细胞体水平的相互作用。使用的技术和这些途径的整合代表了了解心脏神经控制的最具创新性的尝试曾经进行过。了解这些途径有可能加速疗法的发展将能够精确靶向中性结构，并指导方法重新使用已经可用用于治疗目的的疗法（例如神经刺激剂）。最终，这些方法必须开发新颖，有效且负担得起的干预措施，以治疗和预防心脏病和突然心脏死亡。