Neurobiology of the Bronchopulmonary System

支气管肺系统的神经生物学

• 批准号: 10357939
• 负责人: Bradley Joel Undem
• 金额: $ 93.81万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2028-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10357939
• 关键词: Adult; Airway Disease; Animals; Asthma; Autacoids; Award; Basic Science; Biology; C Fiber; Chemicals; Chronic; Chronic Obstructive Pulmonary Disease; Clinical Research; Coughing; Disease; Functional disorder; Funding; Grant; Human; Hyperactivity; Image; Infection; Inflammation Mediators; Inflammatory; Laboratories; Lead; Life; Light; Mentors; Methodology; Methods; Modernization; Nature; Nerve; Nervous system structure; Neurobiology; Neuronal Plasticity; Neurons; Neurosciences; Neurosciences Research; Play; Research Personnel; Respiratory System; Role; Secondary to; Sodium Channel; System; Techniques; Technology; Virus Diseases; Visceral; afferent nerve; airway hyperresponsiveness; airway inflammation; critical period; cytokine; interest; nerve supply; neurophysiology; new therapeutic target; respiratory; user-friendly; voltage

Project Summary/ Abstract Basic and clinical research over the past decade is shedding new light on the major role played by the nervous system in respiratory pathophysiology, in particular in the “hypertussivity” associated with chronic unproductive cough, in the “airways hyperresponsiveness”” associated with of asthma, and in the airway narrowing and secretions associated with COPD. The evidence supports the hypothesis that these hyperactive disorders are in part secondary to dysregulation of vagal afferent C-fibers that comprise some 75% of the nerves within the respiratory tract. This grant aims to advance our understanding of the nature of the inflammatory mediators (autacoids and cytokines) responsible for activating airway C-fibers and the specific ionic mechanisms underlying this activity. This R35 will replace my two active R01 grants: R01 HL137807 “Mechanisms of Inflammatory Activation of Vagal C-Fibers in the Respiratory Tract” and R01HL122228 “Control of Airway Sensory Nerve Function by Voltage- Gated Sodium Channel Subtypes.” The R35 funding will allow us to go beyond the aims of the R01 grants that focus on healthy animals, and delve into the mechanisms that lead to the neuroplasticity associated with airway inflammation. In particular, we propose to evaluate the neuroplasticity in the afferent nervous system that accompanies viral infection during early life “critical periods” with the hypothesis that such infections cause persistent neuroplastic changes. These changes lead to a hyperreactive neurophysiological state that can last into adulthood. This grant will also allow us to continue to advance more user-friendly technologies for studying airway nerves by taking advantage of modern imaging methodologies. These methods will not only serve to advance our own studies, they will also likely be exported to other laboratories interested in visceral neuroscience in general, and airway neuroscience in particular. We will also continue to advance our techniques and studies into the study of human bronchial innervation. Finally, the award will help keep the path paved for continued mentoring of young investigators interested in pursuing airway neuroscience research.

项目摘要/摘要 过去十年中的基础和临床研究正在为发挥的主要作用提供新的启示 通过呼吸病理生理学的神经系统，特别是在“高血压”中 与慢性非生产性咳嗽有关，在“气道高反应性”中 与哮喘以及气道狭窄和分泌物有关 COPD。证据支持以下假设 继发于迷走神经C纤维的失调，完成了约75％的神经 在呼吸道内。这项赠款旨在提高我们对 炎症介质（自闭症和细胞因子）负责激活气道C纤维和 该活性的基本特定离子机制。此R35将替换我的两个主动R01 赠款：R01 HL137807“迷走神经C纤维的炎症激活机制 呼吸道”和R01HL122228“通过电压控制气道感觉神经功能 封闭的钠通道子类型。“ R35资金将使我们超越了 R01授予专注于健康的动物，并深入研究导致该机制 与气道感染相关的神经可塑性。特别是，我们建议评估 传入神经系统中涉及病毒感染的神经可塑性 “关键时期”，假设这种感染会导致持续的神经塑性变化。 这些变化会导致一种可以持续到成年的高反应性神经生理状态。 这笔赠款还将使我们能够继续推进更多用户友好的技术 气道神经通过利用现代成像方法。这些方法不会 仅有助于推进我们自己的学业，他们也可能会出口到其他实验室 对一般的内脏神经科学感兴趣，尤其是气道神经科学。我们将 还继续将我们的技术和研究推进到人支气管的研究 神经。最后，该奖项将有助于保持粘贴的道路，以继续对年轻人的持续进行心理 有兴趣追求气道神经科学研究的调查人员。