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: 10209378
• 负责人: Lilla Zollei
• 金额: $ 72.56万
• 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/10209378
• 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.

猝死综合征（SIDS）是工业化后昆虫后婴儿死亡率的主要原因 今天的国家。通常发生在睡眠期间 - 不愿意，在睡眠期间发生 本身，或在正常婴儿睡眠期间发生的睡眠和醒来之间发生的许多过渡之一。一个 今天的主要假设是唤醒赤字假设：小岛屿发展中国家或一部分小径是由于失败 在关键的发育时期，在睡眠期间，升高的唤醒网络（AAN）升至威胁生命的压力源。 唤醒被认为是意识的基本要素，也是恢复至关重要的 通过为重要过程提供令人兴奋的动力，在呼吸和心血管挑战期间体内稳态 睡觉。 AAN与皮质和皮层下网络相互联系，以调节 稳态反应由与脑干和边缘节点的连通性组成。我们的实验室有 在过去的二十年中，有证据表明5-羟色胺（5-HT）缺陷主要集中在 我们的脑干Aan中鼻髓质网状形成的细胞学定义区域 称为推定的“ SIDS的核心病变”（CLS）。在此R01应用程序中，我们建议测试两倍 假设CL中的核心核彼此具有纤维互连，并且具有一个或多个 脑干内外已知的AAN的核心，因此证明它们是解剖学的一部分 aan;并且在SIDS病例中，血清素能CL中存在结构性解剖异常 与年龄匹配的尸检对照相比。我们将通过扩散拖拉机和 在空前的空间分辨率下以及5-HT免疫细胞化学的光学相干断层扫描 验尸婴儿大脑从出生到生命第一年结束，即小岛屿发展中国家的风险时期。这项工作是 预计将产生重大的积极影响。通过确定推定的核心CL作为不可或缺的一部分 涉及髓质5-HT神经元的AAN，它将为SIDS中有针对性的未来大脑研究奠定基础， 使我们更接近SID和特定预防策略的最终原因。