VENTRAL MEDULLA, BREATHING, AND CENTRAL CHEMORECEPTION

腹延髓、呼吸和中枢化学感受器

• 批准号: 6430009
• 负责人: EUGENE Edward NATTIE
• 金额: $ 23.61万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6430009
• 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.

我们提出，小吻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 项目我们将在两个发育中的仔猪中实验破坏 时代，人类弓形核的同源物发现异常 席德受害者。建议该同源物包含逆转录酶 核（RTN）和副锥虫区域，髓质区域和 尾腔外侧髓质的中央化学感受器区域。在 成年动物，RTN/parapyramidal和Raphe区域的破坏是 已知会降低呼吸输出和敏感性 对增加二氧化碳的呼吸反应。大小 麻醉的影响更大。外周化学感受器的神经 放大了成年动物中这种破坏的有害影响； 当在具有完整脑干功能的新生动物中进行时， 导致不足衰减，更频繁的呼吸暂停和死亡。我们将在 具有和没有完整颈体的杂交小猪，改变 通过微注射1）兴奋性氨基 酸神经毒素可产生病变，2）毒桃和离子型 谷氨酸激动剂/拮抗剂和甲状腺激素释放激素。 基线状态下的神经输出和血压及其血压 将测量对高碳酸盐和窒息的反应。在 有或没有完整的颈动脉 身体，我们将检查弧形同源病变对 自然清醒和睡眠期间的呼吸和血压 对高碳酸盐和窒息的反应。我们的目标是检查 弧形同源神经元和颈动脉体输入的相对作用在 在没有麻醉和自然的情况下呼吸和血压 睡眠和清醒。关于SIDS的三重风险模型 发病机理，我们是1）通过实验创建脆弱性 在我们的病变或注射剂中，2）两个单独的发育年龄，以及 3）检查，作为外源应力，对高碳酸盐和窒息的反应 在有和没有传入的输入的情况下睡觉和睡眠 身体。