PROTECTIVE RESPONSES AND BRAINSTEM ANALYSIS IN SUDDEN INFANT DEATH SYNDROME

婴儿猝死综合症的保护性反应和脑干分析

• 批准号: 6581884
• 负责人: HANNAH C KINNEY
• 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: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6581884
• 关键词: apnea; autoradiography; brain mapping; brain stem; caudate nucleus; human tissue; hypercapnia; hypothalamus; hypoxia; infant human (0-1 year); neurochemistry; neurotoxins; neurotransmitter receptor; postmortem; radiotracer; respiration regulatory center; sudden infant death syndrome

The overall hypothesis of the program project is that the sudden infant death syndrome (SIDS), or a subset of SIDS, is due to developmental abnormalities of the ventral medulla in the brainstem that interfere with normal protective responses to potentially life-threatening, but often occurring, events during sleep, such as hypoxia, hypercapnia, and apnea. Recently we reported neurotransmitter receptor binding deficiencies in SIDS victims in the arcuate nucleus, a region considered homologous to neurons located on the ventral medullary surface in cats that are responsible for the protective responses to hypercapnia and asphyxia. A lesion in the arcuate nucleus could be the only defect in SIDS victims, or a group of SIDS victims. Given the multiple and complex brainstem circuits that underlie protective response to hypoxia, hypercapnia, and apnea, however, a lesion in the arcuate nucleus could be but one of a group of disorders in brainstem protective responses, or alternatively, a central link in a chain of brainstem abnormalities that result in sudden infant death. In this project, we will test the hypothesis that neurotransmitter receptor binding abnormalities in the arcuate nucleus are part of a complex of neurochemical abnormalities in brainstem components related to protective responses to hypoxia, hypercapnia, and apnea. Our Specific Aims are: 1) To determine if there are neurochemical differences between SIDS and age-matched control brainstems in sites related to protective responses, e.g., in the caudal raphe; and 2) To determine if the putative abnormality in neurotransmitter receptor binding in sites related to protective responses correlate with abnormal 3H-kainate binding to kainate receptors in the arcuate nucleus in the same SIDS cases. Quantitative tissue receptor autoradiography will be used. This project would advance our understanding of the role of the brainstem in the pathogenesis of sudden death in SIDS victims.

该计划项目的总体假设是突然的婴儿 死亡综合征（SIDS）或SIDS的一部分是由于发育 脑干中腹侧髓质的异常 对潜在威胁生命的正常保护反应，但通常 发生在睡眠期间的事件，例如缺氧，高碳酸腹泻和呼吸暂停。 最近，我们报道了神经递质受体结合缺陷 SIDS受害者在弧形核中，一个被认为与 位于猫的腹侧髓质表面的神经元 负责对高碳酸盐和窒息的保护性反应。一个 弓形核中的病变可能是小岛屿发展中国家的唯一缺陷，或者 一群小岛受害者。给定多个脑干电路 这是对缺氧，高碳酸盐和呼吸暂停的保护性反应， 但是，弧形核的病变可能只是一组 脑干保护反应中的疾病，或者是中心的 脑干异常的链接导致突然婴儿 死亡。在这个项目中，我们将测试神经递质的假设 弧形核中受体结合异常是A的一部分 与 对缺氧，高碳酸盐和呼吸暂停的保护性反应。我们的具体目标 是：1）确定SID之间是否存在神经化学差异 和年龄匹配的控制脑干 响应，例如，在尾raphe中； 2）确定是否推定 神经递质受体结合的异常与与之相关的位点 保护性反应与与海谷酸盐的异常3H kainate结合相关 在相同的SIDS病例中，弧形核中的受体。定量 将使用组织受体放射自显影。这个项目将进步 我们对脑干在发病机理中的作用的理解 小岛屿发展中国家的突然死亡。