VENTRAL MEDULLA AND THE SUDDEN INFANT DEATH SYNDROME

我们的总体假设是，婴儿猝死综合征（SIDS），或 SIDS的一个子集，是由于腹侧的发育异常， 干扰正常的保护性心肺反应 潜在的危及生命的，但经常发生的，睡眠期间的事件， 如缺氧、高碳酸血症和呼吸暂停。我们最近在小岛屿发展中国家报道， 患者弓状神经递质受体结合缺陷 核，其中包含腹侧髓质表面神经元， 被认为与位于猫的类似区域的神经元同源， 对高碳酸血症和窒息的保护性反应所必需的。我们 提出一个婴儿死于SIDS的三重风险模型 只有当他/她拥有：1）潜在的脆弱性，例如，一个 异常腹侧髓质; 2）在关键时期， 自我平衡控制的发展，即，早期婴儿期; 3） 外源性应激源，例如，体位性窒息将对这一模式进行审查 在项目I-III中，在去大脑仔猪和慢性 在清醒和自然睡眠期间的仪器小猪。在项目I中， 我们将定义弓形同源物在心肺功能中的作用， 在仔猪发育早期进行对照，并确定效果 弓形同源物的结构和神经化学损伤， 对高碳酸血症和窒息的反应在项目II中，我们将描述 仔猪缺氧保护性应激反应的机制， 特别是双相反应的抑郁阶段， 通过喘息进行自动复苏在项目III中，我们将确定 三叉神经、上级喉神经和肋间神经的作用 在室内空气中对弓形同源病变仔猪的刺激 暴露、高碳酸血症和缺氧。在项目IV中，我们将定义 人类弓形虫的细胞和化学构造比较解剖学 细胞核和仔猪同源物。项目五的目标是， 项目一至四提供的关于小岛屿发展中国家异常情况定义的资料 脑干，除了弓状核中的那些。助理 行政核心将提供必要的行政框架。 B。解剖核心将提供细胞和神经化学服务， 动物和人类脑干研究。梭动物生理学核心将 提供一个动物研究实验室，项目I-IV将 由个别研究人员进行。该计划将推动我们的 了解腹侧延髓异常在 SIDS的发病机制。

Our overall hypothesis is that the sudden infant death syndrome (SIDS), or a subset of SIDS, is due to developmental abnormalities of the ventral medulla that interfere with normal protective cardiorespiratory responses to potentially life-threatening, but often occurring, events during sleep, such as hypoxia, hypercapnia, and apnea. We recently reported in SIDS victims neurotransmitter receptor binding deficiencies in the arcuate nucleus, which contains ventral medullary surface neurons that are considered homologous to neurons located in similar areas in cats that are necessary for the protective responses to hypercapnia and asphyxia. We propose a triple-risk model of SIDS in which an infant will die of SIDS only if he/she possesses: 1) an underlying vulnerability, e.g., an abnormality in the ventral medulla; 2) a critical period in the development of homeostatic control, i.e., early infancy; and 3) an exogenous stressor, e.g., positional asphyxia. This model will be examined in Projects I-III, both in decerebrate piglets and in chronically instrumented piglets during wakefulness and natural sleep. In Project I, we will define the role of the arcuate homologue in cardiorespiratory control in the piglet across early development, and determine the effect of structural and neurochemical lesions of the arcuate homologue on response to hypercapnia and asphyxia. In Project II, we will delineate in piglets the mechanisms of protective ventilatory response to hypoxia, especially the depressive phase of the biphasic response and autoresuscitation by gasping. In Project III, we will determine the effects of trigeminal, superior laryngeal, and intercostal nerve stimulation in piglets with arcuate homologue lesions during room air exposure, hypercapnia, and hypoxia. In Project IV, we will define the comparative cyto-and chemoarcitectonic anatomy of the human arcuate nucleus and the piglet homologue. In Project V, the objective is to apply information from Projects I-IV in the definition of abnormalities in SIDS brainstems, in addition to those in the arcuate nucleus. The A. Administrative Core will provide the necessary administrative framework. The B. Anatomy Core will provide cellular and neurochemical services for animal and human brainstem studies. The C. Animal Physiology Core will provide an animal research laboratory in which Projects I-IV will be performed by the individual investigators. This program should advance our understanding of the role of ventral medullary abnormalities in the pathogenesis of SIDS.