CSF AND THE CENTRAL CHEMICAL CONTROL OF BREATHING

CSF 和呼吸的中枢化学控制

• 批准号: 7213327
• 负责人: EUGENE Edward NATTIE
• 金额: $ 41.94万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7213327
• 关键词: Acidosis; Agonist; Animals; Arousal; Blood Pressure; Blood gas; Body Temperature; Brain Stem; Breathing; Caliber; Carbon Dioxide; Cell Nucleus; Chemicals; Chemoreceptors; Chronic; Dialysis procedure; Disease; Electroencephalography; Electromyography; Environmental air flow; Feedback; GABA-A Receptor; Homologous Gene; Injection of therapeutic agent; Length; Location; Measurement; Measures; Microdialysis; Modeling; Morbidity - disease rate; Muscimol; Neurons; Neurophysiology - biologic function; Output; Oxygen Consumption; Physical Dialysis; Physiological; Physiology; Rattus; Role; Site; Sleep; Sleep Apnea Syndromes; Source; Structure of nucleus infundibularis hypothalami; Sudden infant death syndrome; System; Telemetry; Tissues; Wakefulness; Work; research study; respiratory

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）来自中枢化学感受器的关于CO2水平的反馈，以及2）紧张性“驱动”，部分来自CO2，部分来自包括延髓头端腹外侧（RVLM）的其他来源。 最近的研究表明，1）中枢化学感受存在于脑干的许多位置，2）后斜方核（RTN）是一个关键的RVLM网站，提供化学感受和紧张驱动呼吸。 我们问：为什么有这么多的中央 化学感受器部位？ 它们是如何工作的？ 什么是生理作用的 RTN控制呼吸？ 我们将评估化学感受器和RTN功能在睡眠和清醒的慢性未麻醉大鼠模型中使用微透析探针提供物质的RTN（或其他网站）。 探针尖端长度为1 mm，直径为240 μ m，体积为45 nl。 它允许在同一动物的同一部位重复应用神经活性物质，连续测量通气和耗氧量（全身体积描记器）、唤醒状态（EEG、颈部EMG）、体温和血压（遥测），以及在某些情况下，血气和pH。 实验使用该模型; 1/3麻醉的、通气的大鼠，膈活动作为呼吸输出的量度。 对于化学感受生理学的研究，我们在两种模型中通过CO2微透析产生局灶性组织酸中毒。 对于机制的研究，我们改变神经功能的注射/透析局灶性酸中毒在麻醉大鼠。 对于RTN的研究，我们在慢性模型中通过用蝇蕈醇（一种GABA-A受体激动剂）透析可逆地抑制神经元。 中枢化学感受器生理学是重要的; CO2是呼吸控制系统的关键组成部分，疾病中的CO2潴留导致发病。化学感受和RTN功能随唤醒状态而变化，因此可能在睡眠呼吸障碍中很重要，并且RTN被假设为弓状核的动物同源物，在SIDS受害者中被描述为异常。