Neurobiology of the Bronchopulmonary System

项目总结/摘要 过去十年的基础和临床研究正在揭示这一主要作用 在呼吸病理生理学中，特别是在"过度咳嗽"中， 与慢性干咳有关，在"气道高反应性"中， 与哮喘相关，以及与哮喘相关的气道狭窄和分泌物 慢性阻塞性肺病证据支持这样一种假设，即这些多动障碍部分是 继发于迷走神经传入C纤维的失调，迷走神经传入C纤维包括约75%的神经 在呼吸道内。这笔赠款旨在促进我们对自然的理解， 负责激活气道C-纤维的炎症介质（autacoids和细胞因子）， 这一活动背后的特定离子机制。这个R35将取代我的两个活跃的R01 授予：R01 HL 137807 "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- 门控钠通道亚型。" R35资金将使我们能够超越 R01赠款，重点是健康的动物，并深入研究的机制，导致 与气道炎症相关的神经可塑性。特别是，我们建议评估 在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”的假设，这种感染引起持续的神经可塑性变化。 这些变化导致一种过度反应的神经生理状态，这种状态可以持续到成年期。 这笔赠款还将使我们能够继续推进更方便用户的技术， 利用现代影像学方法对气道神经进行检查。这些方法不会 这些研究成果不仅有助于推进我们自己的研究，而且可能会出口到其他实验室。 对内脏神经科学感兴趣，特别是气道神经科学。我们将 我们还将继续推进我们的技术和研究，以研究人类支气管炎。 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。 研究人员对进行气道神经科学研究感兴趣。

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.