Neurobiology of the Bronchopulmonary System

支气管肺系统的神经生物学

• 批准号: 10579184
• 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/10579184
• 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; Life; Mentors; Methodology; Methods; Modernization; Nature; Nerve; Nervous System; 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.

项目概要/摘要 过去十年的基础和临床研究正在揭示其所发挥的主要作用 呼吸病理生理学中的神经系统，特别是“过度咳嗽” 与慢性干咳有关，即“气道高反应性” 与哮喘有关，以及与气道狭窄和分泌物有关 慢性阻塞性肺病。证据支持这样的假设：这些多动症部分是由于 继发于迷走神经传入 C 纤维（约占神经的 75%）的失调 呼吸道内。这笔赠款旨在增进我们对自然现象本质的理解 炎症介质（自体激素和细胞因子）负责激活气道 C 纤维和 该活动背后的特定离子机制。这个 R35 将取代我的两个现用 R01 拨款：R01 HL137807“迷走神经 C 纤维炎症激活机制” 呼吸道”和 R01HL122228“通过电压控制气道感觉神经功能- 门控钠通道亚型。” R35 资金将使我们能够超越 R01 资助重点关注健康动物，并深入研究导致健康动物的机制 与气道炎症相关的神经可塑性。我们特别建议评估 生命早期伴随病毒感染的传入神经系统的神经可塑性 “关键时期”假设此类感染会导致持续的神经塑性变化。 这些变化会导致过度反应的神经生理状态，这种状态可能持续到成年期。 这笔赠款还将使我们能够继续推进更多用户友好的研究技术 利用现代成像方法来观察气道神经。这些方法不会 仅用于推进我们自己的研究，它们也可能被导出到其他实验室 对内脏神经科学特别感兴趣，特别是气道神经科学。我们将 还继续将我们的技术和研究推进到人类支气管的研究中 神经支配。最后，该奖项将有助于为继续指导年轻人铺平道路 对气道神经科学研究感兴趣的研究人员。