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.

我们认为SIDS是由腹侧髓质异常引起的