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（SIDS），或SIDS的一个子集，是由于发育 脑干腹侧髓质异常， 对潜在的生命威胁的正常保护反应，但通常 在睡眠期间发生的事件，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， SIDS受害者在弓状核，一个区域被认为是同源的， 位于猫腹侧延髓表面的神经元 负责对高碳酸血症和窒息的保护性反应。一 弓状核病变可能是SIDS患者的唯一缺陷，或 一群小岛屿发展中国家的受害者考虑到复杂的脑干回路 这是对缺氧、高碳酸血症和呼吸暂停的保护性反应的基础， 然而，弓状核中的病变可能只是一组中的一个， 脑干保护性反应障碍，或者中枢神经系统疾病， 脑干异常链中的一个环节， 死亡在这个项目中，我们将测试神经递质 弓状核中的受体结合异常是 脑干成分神经化学异常复合体 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SIDS之间是否存在神经化学差异 与年龄匹配的对照脑干中与保护性 响应，例如，（2）确定是否存在假定的 神经递质受体结合异常 保护性反应与3 H-红藻氨酸与红藻氨酸结合异常相关 在同一SIDS病例中，弓状核中的受体。定量 将使用组织受体放射自显影术。该项目将推进 我们对脑干在脑梗死发病机制中的作用的理解 SIDS受害者的突然死亡