VENTRAL MEDULLA, BREATHING, AND CENTRAL CHEMORECEPTION

腹延髓、呼吸和中枢化学感受器

• 批准号: 6302061
• 负责人: EUGENE Edward NATTIE
• 金额: $ 20.4万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6302061
• 关键词: blood pressure; brain mapping; brain stem; carotid body; chemoreceptors; decerebration; denervation; developmental neurobiology; disease /disorder model; excitatory aminoacid; glutamate receptor; hypercapnia; hypothalamus; hypoxia neonatorum; microinjections; muscarinic receptor; neurotoxins; newborn animals; respiration regulatory center; sleep; sudden infant death syndrome; swine; thyrotropin releasing hormone; wakefulness

We proposed that SIDS results from abnormalities in the ventral medulla that interfere with normal protective cardiorespiratory reflexes. In this project we shall disrupt experimentally in piglets, at two developmental times, the homologue of the human arcuate nucleus found to be abnormal in SIDS victims. This homologue is proposed to contain the retrotrapezoid nucleus (RTN) and parapyramidal regions, the medullary raphe region, and the central chemoreceptor regions of the caudal ventrolateral medulla. In adult animals, disruption of the RTN/parapyramidal and raphe regions is known to diminish respiratory output and the sensitivity of the respiratory response to increased carbon dioxide. The magnitude of the effects is greater in anesthesia. Denervation of peripheral chemoreceptors magnifies the deleterious effects of this disruption in adult animals; when performed in newborn animals with intact brainstem function, it results in hypoventilation, more frequent apneas, and death. We shall, in the decerebrate piglet with and without intact carotid bodies, alter arcuate homologue function by microinjection of 1) an excitatory amino acid neurotoxin to produce lesions, and 2) muscarinic and ionotropic glutamate agonists/antagonists, and thyrotropin releasing-hormone. Phrenic nerve output and blood pressure in the baseline state and their responses to hypercapnia and asphyxia will be measured. In the unanesthetized chronic piglet preparations with and without intact carotid bodies, we will examine the effect of arcuate homologue lesions on breathing and blood pressure during natural wakefulness and sleep and on the responses to hypercapnia and asphyxia. Our goal is to examine the relative roles of arcuate homologue neurons and carotid body inputs on breathing and blood pressure in the absence of anesthesia and in natural sleep and wakefulness. In respect to the Triple Risk Model for SIDS pathogenesis, we are 1) experimentally creating a vulnerability by means of our lesions or injections, at 2) two separate developmental ages, and 3) examining, as exogenous stresses, responses to hypercapnia and asphyxia in wakefulness and sleep with and without afferent input from the carotid body.

我们认为 SIDS 是由腹侧髓质异常引起的 干扰正常的保护性心肺反射。在这个 我们将在仔猪中进行实验性破坏的项目，在两个发育阶段 次，人类弓状核的同源物被发现异常 小岛屿发展中国家 (SIDS) 受害者。该同系物被提议包含反梯形 核（RTN）和锥体旁区域、髓缝区域和 尾部腹外侧延髓的中央化学感受器区域。在 成年动物，RTN/锥体旁和中缝区域的破坏是 已知会减少呼吸输出量和敏感性 对二氧化碳增加的呼吸反应。的大小 麻醉效果更大。外周化学感受器的去神经支配 放大这种破坏对成年动物的有害影响； 当在脑干功能完整的新生动物中进行时， 导致通气不足、更频繁的呼吸暂停和死亡。我们将在 具有或不具有完整颈动脉体的去大脑仔猪，改变 通过显微注射 1) 兴奋性氨基实现弓形同系物功能 酸性神经毒素产生损伤，2) 毒蕈碱和离子型 谷氨酸激动剂/拮抗剂和促甲状腺素释放激素。 基线状态下膈神经输出量和血压及其变化 将测量对高碳酸血症和窒息的反应。在 带或不带完整颈动脉的未麻醉慢性仔猪制剂 身体，我们将检查弓形同源病变对 自然清醒和睡眠期间的呼吸和血压 对高碳酸血症和窒息的反应。我们的目标是检查 弓状同源神经元和颈动脉体输入的相对作用 在没有麻醉和自然情况下的呼吸和血压 睡眠和清醒。关于小岛屿发展中国家的三重风险模型 发病机制，我们1）通过以下方式实验性地创造一个漏洞 我们的病变或注射，在 2) 两个不同的发育年龄，以及 3) 作为外源性应激，检查对高碳酸血症和窒息的反应 清醒时和睡眠时有或没有颈动脉传入输入 身体。