Brainstem Arousal Network in Human Consciousness: Healthy development vs SIDS

人类意识中的脑干唤醒网络：健康发展与 SIDS

• 批准号: 10397639
• 负责人: Lilla Zollei
• 金额: $ 70.49万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10397639
• 关键词: 1 year old; 3-Dimensional; Adult; Age; Age-Months; Anatomy; Arousal; Asphyxia; Autopsy; Awareness; Axon; Beds; Birth; Brain; Brain Stem; Cardiovascular system; Cause of Death; Cell Density; Cell Nucleus; Cells; Cessation of life; Complex; Conscious; Cytology; Defect; Deformity; Developed Countries; Development; Diffusion; Early Intervention; Elements; Environmental Risk Factor; Failure; Fiber; Foundations; Future; Graph; Growth; Homeostasis; Human; Hypercapnia; Hypotension; Hypothalamic structure; Hypoxia; Image; Infant; Intervention; Investigation; Laboratories; Lesion; Life; Link; Location; Magnetic Resonance Imaging; Maintenance; Maps; Measures; Mediating; Microscopic; Microscopy; Neuroanatomy; Neurons; Optical Coherence Tomography; Optics; Pathogenesis; Pathway interactions; Pattern; Positioning Attribute; Prevention strategy; Process; Resolution; Reticular Formation; Risk; Serotonin; Site; Sleep; Source; Structure; Structure of nucleus infundibularis hypothalami; Sudden infant death syndrome; Surface; Techniques; Testing; Time; Tissues; United States; Work; algorithm development; basal forebrain; brain research; critical developmental period; density; heavy nuclei; human disease; immunocytochemistry; in vivo; mind control; multidisciplinary; neural network; neuroimaging; neuropathology; novel; postneonatal mortality; relating to nervous system; respiratory; response; restoration; sleep position; statistics; stressor; tool; tractography; ultra high resolution

Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant mortality in industrialized nations today. Typically it occurs during a sleep period – unwitnessed, it is presumed to occur during sleep itself, or during one of the many transitions between sleep and waking that occur during normal infant sleep. A leading hypothesis today is the arousal deficit hypothesis: SIDS, or a subset of SIDS, is due to a failure in the ascending arousal network (AAN) to a life-threatening stressor during sleep in a critical developmental period. Arousal is considered an essential element of consciousness, as well as essential for restoration of homeostasis during respiratory and cardiovascular challenges by providing excitatory drive to vital processes from sleep. The AAN is interconnected with cortical and subcortical networks that regulate the integration of homeostatic responses, comprised of connectivity with brainstem and limbic nodes. Our laboratory has provided evidence over the last two decades that serotonin (5-HT) defects are concentrated mainly in a cytologically defined region of the rostral medullary reticular formation in the AAN of the brainstem which we call the putative "core lesions of SIDS" (CLS). In this R01 application, we propose to test the two-fold hypothesis that the core nuclei in the CLS have fiber interconnections with each other and with one or more known nuclei of the AAN within and above the brainstem, thereby demonstrating they are anatomically part of the AAN; and that there are structural anatomic abnormalities in the serotonergic CLS in the SIDS cases compared to the age-matched autopsy controls. We will perform ex vivo MRI with diffusion tractography and optical coherence tomography at unprecedented spatial resolution along with 5-HT immunocytochemistry in postmortem infant brains from birth to the end of the first year of life, the period of risk for SIDS. This work is expected to have a significant positive impact. By establishing the putative core CLS as an integral part of the AAN involving medullary 5-HT neurons, it will provide the foundation for targeted future brain research in SIDS, bringing us closer to the ultimate cause(s) of SIDS and specific preventive strategies.

婴儿猝死综合征（SIDS）是工业化国家新生儿后期死亡的主要原因， 今天的国。通常它发生在睡眠期间-没有目击者，它被认为发生在睡眠期间 在正常婴儿睡眠期间发生的睡眠和清醒之间的许多过渡之一期间。一 当今的主要假设是觉醒缺陷假设：SIDS或SIDS的一个子集是由于 上升唤醒网络（AAN）在睡眠中的一个关键的发展时期威胁到生命的压力。 觉醒被认为是意识的一个基本要素，也是恢复意识的必要条件。 通过为生命过程提供兴奋驱动，在呼吸和心血管挑战期间保持体内平衡 从睡梦中醒来AAN与皮质和皮质下网络相互连接，这些网络调节 稳态反应，包括与脑干和边缘系统节点的连接。本实验室 在过去的二十年里，他提供了证据，证明血清素（5-HT）缺陷主要集中在 在脑干的AAN中，细胞学定义的头端延髓网状结构区域，我们 称之为“小岛屿发展中国家的核心病变”（CLS）。在此R 01应用程序中，我们建议测试两重 假设CLS中的核心核彼此之间以及与一个或多个核之间具有纤维互连， 脑干内和脑干上方的AAN的已知核，从而证明它们是解剖学上的一部分， AAN; SIDS病例中的肾上腺素能CLS存在结构解剖异常 与年龄匹配的尸检对照组相比。我们将使用弥散纤维束成像进行离体MRI， 光学相干断层扫描在前所未有的空间分辨率沿着与5-羟色胺免疫细胞化学， 尸检婴儿大脑从出生到生命的第一年结束，这是SIDS的风险期。这项工作是 预计将产生重大的积极影响。通过将假定的核心CLS确立为 AAN涉及延髓5-HT神经元，它将为SIDS的未来脑研究提供基础， 使我们更接近小岛屿发展中国家的根本原因和具体的预防战略。