VENTRAL MEDULLA AND THE SUDDEN INFANT DEATH SYNDROME

我们的总体假设是婴儿猝死综合征(SID)，或 小儿麻痹症的一个子集，是由于腹侧发育异常 干扰正常保护性心肺反应的延髓 可能危及生命，但经常发生在睡眠中的事件， 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了 受害者弓状体区神经递质受体结合缺陷 核，它包含腹侧延髓表面神经元， 被认为与猫中位于相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 提出婴儿将死于小岛屿发展中国家的三重风险模型 仅当他/她拥有：1)潜在的漏洞，例如 延髓腹侧的异常；2)延髓腹侧的关键期。 动态平衡控制的发展，即早期婴儿期；3)和 外源性应激源，如体位窒息。我们将对此模型进行测试 在项目I-III中，无论是去大脑仔猪还是慢性去大脑仔猪 在清醒和自然睡眠期间，仪表化的小猪。在项目I中， 我们将确定弓形同系物在心肺功能中的作用 在仔猪早期发育过程中控制，并确定效果 弓状同系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，我们将在 仔猪对低氧的保护性呼吸反应机制， 尤其是双相反应的抑郁阶段和 通过喘气进行自动复苏。在项目III中，我们将确定 三叉神经、喉上神经和肋间神经的作用 室内空气中弓形同源病变对仔猪的刺激作用 暴露、高碳酸血症和缺氧。在项目IV中，我们将定义 人体弓状回的比较细胞和化学结构解剖学 细胞核和仔猪的同源基因。在项目五中，目标是应用 小岛屿发展中国家异常情况定义项目一至四提供的资料 除弓状核外，还有脑脊束核。A。 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。C.动物生理学核心将 提供一个动物研究实验室，项目I-IV将在其中 由个人调查员执行。这一计划应该会促进我们的 对延髓腹侧异常在脑梗塞中作用的认识 小儿麻痹症的发病机制。

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.