Airway sensors with myelinated afferents

具有髓鞘传入神经的气道传感器

基本信息

批准号：
8597360
负责人：
JERRY (Jun) YU
金额：
--
依托单位：
LOUISVILLE VA MEDICAL MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-10-01 至 2014-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8597360
关键词：
Acute Lung Injury Address Adult Respiratory Distress Syndrome Asthma Behavior Bronchoconstriction C Fiber Cardiopulmonary Chemicals Chronic Obstructive Airway Disease Classification Clinical Confocal Microscopy Coughing Data Development Disease Dyspnea Exhibits Fiber Foundations Heart Diseases Heart failure Inflammation Knowledge Laboratories Lung Lung diseases Mechanics Mechanoreceptors Microscopy Morphology Mucous body substance Neurons Patients Physiological Play Process Pulmonary Heart Disease Research Role Sensory Sensory Receptors Staining method Stains Structure Structure of parenchyma of lung Structure-Activity Relationship Surveys System Techniques Testing Tissues Trachea Transducers Vagus nerve structure Veterans improved neuromechanism operation public health relevance pulmonary function receptive field receptor receptor function relating to nervous system response sensor sensory integration sensory mechanism transmission process

项目摘要

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to identify the unknown morphology and pathophysiological functions of pulmonary sensory receptors, potentially benefiting more than 30 million patients with chronic obstructive pulmonary disease (COPD) and other pulmonary diseases in the US, including veterans. Dyspnea, bronchial inflammation, hyperreactivity, coughing, and mucus secretion occur when airway sensory receptors are activated. These are common clinical manifestations of pulmonary disorders; however, the underlying neural mechanisms remain unclear, in part because our knowledge of airway receptor morphology and sensory behavior is limited. Increasing evidence points to important roles of myelinated airway receptors in pulmonary diseases. In this application, we will test the hypothesis that vagal airway sensory units are not only transducers but also processors. Sensory units' behaviors depend on their structures. In addition, a single unit may contain homogeneous or heterogeneous types of receptors, providing varied, mixed behavior. In this application, we will address three specific aims to characterize the morphology and sensory behavior of myelinated airway receptors. 1) To identify different morphological structures of myelinated airway receptors by examing receptor morphology by immunohistochemical or neural tracing techniques combined with confocal microscopy. 2) To assign a specific receptor structure to physiologically defined classes of receptors, by first electrophysiologically characterizing each known receptor type, then tissue in the receptive field will be isolated, dissected, and immunohistochemically stained for receptor morphology. 3) To explore mechanosensor structure-function relationships and sensory integration mechansims by examining sensory behavior before and after blocking or stimulating one of the receptors in the unit. Thus, integration mechanisms of sensory units can be explored. Successful completion of these studies will provide important structure-function relationships and establish a comprehensive, objective classification system for the airway receptors. The presence of heterogenous receptors challenges the current view of the airway sensory unit. Transmission of heterogeneous information in a single unit verifies that the unit is not merely a transducer but also a processor. Our data will lay the foundation for future research and facilitate our understanding of the receptor function and their roles in pulmonary diseases and may help improve managements for cardiopulmonary patients suffering from cardiac failure, COPD, asthma, acute lung injury, and other pulmonary diseases. PUBLIC HEALTH RELEVANCE: Airway sensory receptors play important roles in cardiopulmonary diseases. Understanding their mechanisms of operation may help patient management, thus, benefitting a large number of veterans who suffer from cardiac and lung diseases, including cardiac failure, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and asthma.

描述（由申请人提供）：该提案的长期目标是确定肺动物受体的未知形态和病理生理功能，可能使超过3000万慢性阻塞性肺部疾病（COPD）和其他肺部疾病的患者受益于包括退伍军人，包括退伍军人。当激活气道感觉受体时，发生呼吸困难，支气管炎症，过度反应性，咳嗽和粘液分泌。这些是肺部疾病的常见临床表现。但是，潜在的神经机制尚不清楚，部分原因是我们对气道受体形态和感觉行为的了解是有限的。越来越多的证据表明，骨髓气道受体在肺部疾病中的重要作用。在此应用中，我们将测试迷走神经道的感觉单元不仅是传感器，而且是处理器的假设。感官单位的行为取决于其结构。此外，单个单元可能包含均质或异质类型的受体，提供多种多样的混合行为。在此应用程序中，我们将解决三个特定的目标，以表征骨髓气道受体的形态和感觉行为。 1）通过免疫组织化学或神经跟踪技术结合共聚焦显微镜检查，通过检查受体形态来鉴定髓鞘气道受体的不同形态结构。 2）通过先电生理学表征每种已知的受体类型的特定受体结构为生理定义的受体类别，然后将分离，解剖和免疫组织化学染色以进行受体形态。 3）探索机械传感器结构功能关系和感觉积分机制，通过检查阻塞或刺激单元中的一个受体之一之前和之后的感觉行为。因此，可以探索感官单元的集成机制。这些研究的成功完成将提供重要的结构功能关系，并为气道受体建立全面的，客观的分类系统。异源受体的存在挑战了气道感觉单元的当前视图。单个单元中异质信息的传输可验证单元不仅是传感器，而且是处理器。我们的数据将为未来的研究奠定基础，并促进我们对受体功能及其在肺部疾病中的作用的理解，并可能有助于改善患有心脏衰竭，COPD，哮喘，急性肺损伤和其他肺部疾病的心肺患者的管理。公共卫生相关性：气道感觉受体在心肺疾病中起重要作用。了解他们的手术机制可能有助于患者管理，从而使大量患有心脏和肺部疾病的退伍军人受益，包括心力衰竭，急性呼吸窘迫综合征（ARDS），慢性阻塞性肺部疾病（COPD）和哮喘。