CSF AND THE CENTRAL CHEMICAL CONTROL OF BREATHING

CSF 和呼吸的中枢化学控制

• 批准号: 2216220
• 负责人: EUGENE Edward NATTIE
• 金额: $ 26.42万
• 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/2216220
• 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 对于正常功能而言，这取决于机械和化学传入 信息包括 CO2 和/或 H+ 传感中心的信息 化学感受器。 该项目将描述它们的位置、类型 涉及的单个单位以及化学敏感性的机制。 一个新的 方法是注射 1 nl 乙酰唑胺，产生限制性的 持续性脑干组织酸中毒区域（半径<350微米） 麻醉老鼠和猫。 站点（用荧光微珠标记）位于 哪种乙酰唑胺注射液会增加膈活动，确定 化学感受器位置（目前我们知道至少有 3 个）。 这个探头 与多管移液器一起使用进行记录和注射将允许 识别范围内的单一化学敏感单位 乙酰唑胺诱导的组织酸中毒及其体内检查 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梯形的完整性 核（RTN），延髓头端腹外侧区域，位于腹侧 到头侧和中间边界的面核 化学敏感区域。 RTN 在控制 麻醉动物呼吸单侧 RTN 破坏废除 化学敏感性并经常抑制呼吸导致呼吸暂停。 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 RTN 的传入来源 示踪剂并评估 RTN 在刺激反应中的作用 中枢和外周化学感受器以及上呼吸道感受器 上喉传入。 使用多管移液器 记录和注入我们将确定受影响的 RTN 单元类型 每个传入神经元和所涉及的神经递质。 传出效应 RTN 刺激呼吸相关脑干的三大群 将评估神经元及其在长期促进中的作用， 某些形式的膈活动的长期增加 刺激。 单方面 RTN 变更为何如此有效 研究了它在有意识的动物中的作用。 对中枢化学感受和这个小区域的进一步了解 破坏它可以消除化学感受并导致呼吸暂停， 对于全面了解正常生理机能非常重要 呼吸的控制。 在慢性病等情况下这可能很重要 阻塞性肺病，其中呼吸控制系统经常 决定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，并且 最近的研究表明，两名人类受害者的神经元发育不全 髓质区域类似于大鼠和猫的 RTN 区域。