CSF AND THE CENTRAL CHEMICAL CONTROL OF BREATHING

CSF 和呼吸的中枢化学控制

• 批准号: 2766211
• 负责人: EUGENE Edward NATTIE
• 金额: $ 38.07万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-12-01 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2766211
• 关键词: brain mapping; brain stem; carbon dioxide tension; carotid body; cerebrospinal fluid; chemoreceptors; hypothalamus; laboratory rat; medulla oblongata; microdialysis; muscimol; neurochemistry; neuropharmacology; plethysmography; psychic activity level; pulmonary respiration; respiration regulatory center; respiratory acidosis; respiratory reflex

Appropriate breathing requires 1) feedback concerning the level of CO2 from central chemoreceptors, and 2) a tonic 'drive', partly from CO2, and partly from other sources including the rostral ventrolateral medulla (RVLM). Recent work established that 1) central chemoreception is present at many brainstem locations, and 2) the retrotrapezoid nucleus (RTN) is a key RVLM site that provides both chemoreception and a tonic drive to breathe. We ask: Why are there so many central chemoreceptor sites? How do they work? What is the physiological role of the RTN in the control of breathing? We will evaluate chemoreceptor and RTN function during sleep and wakefulness in a chronic unanesthetized rat model using a microdialysis probe to deliver substances to the RTN (or other site). The probe tip is 1 mm in length and 240 mum in diameter, a volume of 45 nl. It allows repeated application of neuroactive substances at the same site in the same animal with continuous measurement of ventilation and oxygen consumption (whole body plethysmograph), arousal state (EEG, nuchal EMG), body temperature and blood pressure (telemetry), and, in some cases, blood gases and pH. Approximately 2/3 of the experiments use this model; 1/3 an anesthetized, ventilated rat with phrenic activity as the measure of respiratory output. For studies of chemoreception physiology, we produce focal tissue acidosis by CO2 microdialysis in both models. For studies of mechanism, we alter neural function by injection/dialysis within the focal region of acidosis in the anesthetized rat. For studies of the RTN, we inhibit neurons reversibly by dialysis with muscimol, a GABA-A receptor agonist, in the chronic model. Central chemoreceptor physiology is significant; CO2 is a key component of the respiratory control system and CO2 retention in disease causes morbidity. Chemoreception and RTN function vary with arousal state, and thus are likely to be important in sleep disordered breathing, and the RTN is hypothesized to be an animal homologue for the arcuate nucleus, described as abnormal in SIDS victims.

适当的呼吸需要1）关于中央化学感受器的二氧化碳水平的反馈，以及2）一种补品“驱动器”，部分来自二氧化碳，部分来自包括the腹腹侧髓质（RVLM）在内的其他来源。 最近的工作确定1）中央化学感受在许多脑干位置存在，2）逆转录核酸核（RTN）是一个关键的RVLM位点，既可以提供化学感受，又提供呼吸的滋补驱动力。 我们问：为什么有这么多中央化学感受器位点？ 他们如何工作？ RTN在呼吸控制中的生理作用是什么？ 我们将使用微透析探针在慢性的一般性大鼠模型中评估睡眠期间的化学感受器和RTN功能，以将物质运送到RTN（或其他位点）。 探针尖端的长度为1毫米，直径为240 MM，体积为45 nl。 它允许在同一动物中重复应用神经活性物质，并连续测量通气和氧气消耗（全身杂质），唤醒状态（EEG，NUCHAL EMG），体温和血压（远程压力），在某些情况下，血液气和血压和pH。大约2/3的实验使用此模型； 1/3用麻醉的通风大鼠具有phrenig活性作为呼吸输出的度量。 为了研究化学感受生理学，我们在两种模型中都通过CO2微透析产生局灶性组织酸中毒。 对于机制的研究，我们通过麻醉大鼠的酸中毒焦点区域内通过注射/透析来改变神经功能。 对于RTN的研究，我们在慢性模型中用墨西酚（Muscimol）（一种GABA-A受体激动剂）抑制神经元。 中央化学感受器生理非常重要。 CO2是呼吸控制系统的关键组成部分，疾病中的二氧化碳保留率会导致发病率。化学感受和RTN功能随唤醒状态而变化，因此在睡眠无序的呼吸中可能很重要，并且假设RTN是弓形核的动物同源物，被描述为SIDS受害者的异常。