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)中枢化学感受器对二氧化碳水平的反馈，2)紧张性‘驱动力’，部分来自二氧化碳，部分来自其他来源，包括头端延髓腹外侧区(RVLM)。最近的工作证实：1)中枢化学接收存在于许多脑干部位，2)斜方后核(RTN)是RVLM的关键部位，它既提供化学接收又提供呼吸的紧张性驱动。我们问：为什么有这么多中央 化学感受器位置？它们是如何工作的？它的生理作用是什么？ RTN在呼吸控制中的作用？我们将使用微透析探头将物质输送到RTN(或其他部位)，在慢性非麻醉大鼠模型中评估化学感受器和RTN在睡眠和清醒期间的功能。探头尖端长1 mm，直径240微米，体积为45nL。它允许在同一动物的同一部位重复应用神经活性物质，并连续测量通风和氧气消耗(全身体积描记仪)、唤醒状态(EEG，颈部肌电)、体温和血压(遥测)，在某些情况下，还测量血气和pH。大约2/3的人 实验使用此模型；1/3的麻醉、通风的大鼠以膈活动作为呼吸输出的量度。为了研究化学感受生理学，我们在两种模型中都通过二氧化碳微透析产生局灶性组织酸中毒。为了研究机制，我们在麻醉大鼠的酸中毒局部区域通过注射/透析改变神经功能。对于RTN的研究，我们在慢性模型中通过使用GABA-A受体激动剂麝香酚透析可逆地抑制神经元。中枢化学感受器生理学意义重大；二氧化碳是呼吸控制系统的关键组成部分，二氧化碳滞留在疾病中会导致发病率。化学接收和RTN功能随着觉醒状态的不同而不同，因此在睡眠障碍呼吸中可能是重要的，RTN被假设为弓状核的动物同源物，在SIDS患者中被描述为异常。