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.

该项目的总体假设是，突然出生的婴儿 死亡综合征(SID)，或SID的子集，是由于发育 脑干腹侧延髓的异常干扰 对潜在威胁生命的正常保护性反应，但通常 睡眠中发生的事件，如缺氧、高碳酸血症和呼吸暂停。 最近我们报道了神经递质受体结合缺陷。 小岛屿发展中国家受害者的弓状核，该区域被认为与 位于猫延髓腹侧表面的神经元 负责对高碳酸血症和窒息的保护性反应。一个 弓状核病变可能是小岛屿发展中国家患者的唯一缺陷，或者 一群小岛屿发展中国家的受害者。考虑到多个复杂的脑干电路 对低氧、高碳酸血症和呼吸暂停的保护性反应， 然而，弓状核中的病变可能只是一组 脑干保护性反应的紊乱，或者，中枢 导致婴儿突然出生的脑干异常链中的联系 死亡。在这个项目中，我们将检验神经递质的假设 弓状核中的受体结合异常是 脑干相关成分的复杂神经化学异常 对缺氧、高碳酸血症和呼吸暂停的保护性反应。我们的具体目标 1)确定小岛屿发展中国家之间是否存在神经化学差异 和年龄匹配的对照组脑组织在与保护性相关的部位 反应，例如，在尾侧中缝；以及2)以确定推定的 神经递质受体结合异常的相关部位 保护反应与~3H-海人藻酸与海人酸结合异常有关 在同一病例中，弓状核中的受体。量化 将使用组织受体放射自显影。这项工程将会推进 我们对脑干在心力衰竭发病机制中作用的认识 小岛屿发展中国家受害者猝死。