CSF AND THE CENTRAL CHEMICAL CONTROL OF BREATHING

CSF 和呼吸的中枢化学控制

• 批准号: 2430629
• 负责人: EUGENE Edward NATTIE
• 金额: $ 29.54万
• 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 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2430629
• 关键词: acetazolamide; acetylcholinesterase; acidity /alkalinity; anesthesia; antiport; brain stem; carbon dioxide; carotid body; cats; cerebrospinal fluid; chemoreceptors; histidine; hypothalamus; imidazole; laboratory rat; laryngeal nerves; membrane transport proteins; neuropharmacology; neurotransmitters; phrenic nerve; pulmonary respiration; respiration regulatory center; respiratory acidosis; respiratory reflex; synapses

The control of breathing involves brainstem rhythm and pattern generators which depend, for normal function, on mechanical and chemical afferent information including that of CO2 and/or H+ sensing central chemoreceptors. This project will describe their locations, the type of single unit involved, and the mechanism of chemosensitivity. A new approach, a 1 nl injection of acetazolamide, produces a circumscribed region of lasting brainstem tissue acidosis (<350 micro in radius) in anesthetized rats and cats. Sites (marked by fluorescent microbeads) at which acetazolamide injection increases phrenic activity identify a chemoreceptor location (we know of at least 3 at present). This probe used with a multi-barrelled pipette for recording and injecting will allow identification of single chemosensitive units within the sphere of acetazolamide induced tissue acidosis and examination in vivo of chemoreceptor mechanisms including the role of synapses, imidazole- histidine, acetylcholinesterase, and the bicarbonate/chloride antiporter. Normal chemosensitivity requires the integrity of the retrotrapezoid nucleus (RTN), a region of the rostral ventrolateral medulla lying ventral to the facial nucleus at the border of the rostral and intermediate chemosensitive areas. The RTN has singular importance in the control of breathing for in anesthetized animals unilateral RTN destruction abolishes chemosensitivity and depresses respiration often to apnea. This project will evaluate the function and importance of the RTN region. It will describe the sources of afferents to the RTN using retrograde anatomical tracers and evaluate the role of the RTN in responses to stimulation of central and peripheral chemoreceptors and to upper airway receptors with superior laryngeal afferents. Using multi-barrelled pipettes for recording and injecting we will determine the RTN unit types affected by each afferent and the neurotransmitter involved. The efferent effects of RTN stimulation on the three major groups of respiratory related brainstem neurons will be evaluated as well as its role in long term facilitation, the prolonged increase of phrenic activity seen with certain forms of stimulation. How unilateral RTN alterations are so effective will be examined as will its role in conscious animals. Further knowledge of central chemoreception and this small region, the destruction of which can abolish chemoreception and result in apnea, is important for having a complete understanding of the normal physiology of the control of breathing. It may be important in situations like chronic obstructive lung disease where the respiratory control system often determines the adaptive response and the Sudden Infant Death Syndrome where abnormalities in chemosensitivity are one etiological hypothesis and recent work has shown, in two human victims, neuronal hypoplasia in a medullary region analogous to the RTN region in rat and cat.

呼吸的控制涉及脑干节律和模式发生器 其正常功能依赖于机械和化学传入 包括CO2和/或H+传感中心的信息 化学感受器 这个项目将描述他们的位置， 涉及的单个单位和化学敏感性的机制。 一个新 方法，注射1 nl乙酰唑胺，产生一个限制性的 持续脑干组织酸中毒区域（半径<350 μ m）， 麻醉的大鼠和猫。 部位（用荧光微珠标记） 乙酰唑胺注射液增加膈神经活动 化学感受器位置（我们目前至少知道3个）。 该探针 使用多管移液管记录和进样， 识别范围内的单个化学敏感单元 乙酰唑胺诱导的组织酸中毒和体内检测 化学感受器机制，包括突触的作用，咪唑- 组氨酸、乙酰胆碱酯酶和碳酸氢盐/氯化物逆向转运蛋白。 正常的化疗敏感性需要后小斜肌的完整性 核（RTN），延髓头端腹外侧区，位于腹侧 至面神经核的吻侧和中间核的边界 化学敏感区 RTN在控制 麻醉动物单侧RTN破坏的呼吸消失 化疗敏感性和抑制呼吸往往呼吸暂停。 这个项目 将评估RTN区域的功能和重要性。 它将 使用逆行解剖学描述传入RTN的来源 示踪剂，并评估RTN的作用，在响应刺激 中枢和外周化学感受器以及上呼吸道感受器， 上级喉传入神经。 使用多管移液管 记录和注入，我们将确定受以下因素影响的RTN单元类型 每一个传入神经和神经递质都参与其中。 的传出效应 RTN刺激对呼吸相关脑干三大群的影响 将评估神经元及其在长期易化中的作用， 膈神经活动的长期增加与某些形式的 刺激. 单方面的RTN变更如何如此有效， 在有意识的动物中，它的作用也将被研究。 进一步了解中央化学感受和这个小区域， 其破坏可消除化学感受并导致呼吸暂停， 重要的是要有一个完整的了解正常的生理 控制呼吸。 这在慢性病等情况下可能很重要， 阻塞性肺疾病，其中呼吸控制系统经常 决定了适应性反应和婴儿猝死综合症 其中化学敏感性异常是一种病因学假设， 最近的研究表明，在两名人类受害者中， 在大鼠和猫中类似于RTN区的延髓区。