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: 6504186
• 负责人: MUSA A HAXHIU
• 金额: $ 24.81万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6504186
• 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抗性受到许多因素的影响，包括神经元驱动器向上气道扩张和收缩肌肉，气道平滑肌和气道脉管系统的变化。在睡眠期间，上气道的活动减少了肌肉，胆碱能流出到气道平滑肌。这并不罕见地导致睡眠阻塞性呼吸暂停和气道功能的恶化。神经解剖学投影，神经递质和介导与睡眠相关的变化的信号通路尚不清楚。该提案包括针对涉及呼吸和气道通气的中央网络的研究。第一部分涉及1）在睡眠过程中激活的CNS细胞组的神经化学组织和轴突预测，2）鉴定睡眠促进部位的目标神经元及其与降低和气道相关的迷走神经元神经元的靶神经元的关系，以及第二部分的神经化学元素，以及3）神经化学的动作范围，该动作均可在3次逐渐变化。扩张和收缩肌肉。 FOS表达将用于鉴定在睡眠期间激活的神经元，研究这些细胞的基本化学神经解剖学，以在睡眠激活的神经元中局部的推定神经递质，并确定这些结构与低型和气道相关的频道和气道相关的前神经神经元之间的途径和连接。这些研究得出的数据将提供与中央网络，神经化学组织以及促进细胞和脑干输出神经元之间通信的化学性质有关的基本信息。结果将直接与我们对睡眠过程中集中介导的呼吸道和气道功能的神经化学机制的理解有关，例如阻塞性睡眠呼吸暂停和夜间哮喘的恶化。