Central determinants of airway instability during sleep

睡眠期间气道不稳定的主要决定因素

• 批准号: 6357121
• 负责人: MUSA A HAXHIU
• 金额: $ 29.24万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6357121
• 关键词: brain mapping; cooperative study; hypoglossal nerve; laboratory rat; neurochemistry; neuroregulation; respiration regulatory center; respiratory airflow disorder; sleep disorders; vagus nerve

The airways, extending from the nares to the alveoli, have a complex geometry and function. Their size, shape, and consequently resistance to airflow is influenced by numerous factors, including changes in neuronal drive to the upper airway dilating and constricting muscles, airway smooth muscles and airway vasculature. During sleep, activity of the upper airway dilating muscles is reduced and cholinergic outflow to airway smooth muscle is increased. This leads not uncommonly to sleep obstructive apnea and worsening of the airway functions. Neuroanatomical projections, neurotransmitters and signaling pathways mediating sleep-related changes are not well understood. This proposal consists of research focused on the central networks involved in regulation of breathing and airway patency during sleep. The first part deals with 1) the neurochemical organization and axonal projections of the CNS cell groups that are activated during sleep, 2) identification of the target neurons of the sleep promoting sites and their relation to hypoglossal and airway related vagal preganglionic neurons, and the second part with 3) the neurochemical organization of neurons that mediate sleep-related modulations of the automatic functions and motor activities of upper airway dilating and constricting muscles. Fos expression will be used to identify neurons activated during sleep, to investigated the basic chemical neuroanatomy of these cells, to co- localized putative neurotransmitters in sleep activated neurons, and to determine pathways and connections between these structures and the hypoglossal and airway related-vagal preganglionic neurons. The data derived from these studies will provide basic information related to central networks, neurochemical organization, and chemical nature of communications between sleep promoting cells and brainstem output neurons. The results will have a direct bearing on our understanding of neurochemical mechanisms underlying centrally mediated respiratory and airway functions during sleep, such as obstructive sleep apnea and the nocturnal worsening of asthma.

从鼻孔延伸到肺泡的气道具有复杂的几何形状和功能。它们的大小、形状以及因此对气流的阻力受到许多因素的影响，包括上呼吸道扩张和收缩肌、气道平滑肌和气道脉管系统的神经元驱动的变化。睡眠时，上气道扩张肌的活动减少，向气道平滑肌输出的胆碱能增加。这通常会导致睡眠阻塞性呼吸暂停和气道功能恶化。神经解剖投影、神经递质和信号通路介导的睡眠相关变化尚未得到很好的理解。这项提议包括集中研究在睡眠中参与呼吸和气道通畅调节的中枢网络。第一部分涉及1)在睡眠中被激活的中枢神经系统细胞群的神经化学组织和轴突投射，2)睡眠促进部位的目标神经元的识别及其与舌下和气道相关的迷走神经节前神经元的关系，第二部分涉及3)介导与睡眠相关的上呼吸道扩张和收缩肌肉自动功能和运动活动调节的神经元的神经化学组织。Fos的表达将用于识别在睡眠中激活的神经元，研究这些细胞的基本化学神经解剖学，在睡眠激活的神经元中共同定位假设的神经递质，并确定这些结构与舌下和气道相关迷走神经节前神经元之间的通路和联系。从这些研究中获得的数据将提供有关中枢网络、神经化学组织以及促进睡眠细胞和脑干输出神经元之间通信的化学性质的基本信息。研究结果将直接影响我们对睡眠中中枢调节的呼吸和气道功能的神经化学机制的理解，如阻塞性睡眠呼吸暂停和夜间哮喘恶化。