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

基本信息

批准号：
10612759
负责人：
Lilla Zollei
金额：
$ 70.88万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
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/10612759
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 Defect Deformity Developed Countries Development Diffusion Early Intervention Elements Environmental Risk Factor Failure Fiber Foundations Future Graph Growth Heating Homeostasis Human Hypercapnia Hypotension Hypothalamic structure Hypoxia Image Infant Intervention Investigation Laboratories Lesion Life Link Live Birth 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 Tissues United States Visualization Work algorithm development basal forebrain brain research critical developmental period density heavy nuclei human disease immunocytochemistry in vivo mind control multidisciplinary neural neural network neuroimaging neuropathology novel postneonatal mortality respiratory response restoration sleep position statistics stressor three-dimensional visualization tissue fixing tool tractography ultra high resolution

项目摘要

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.

婴儿猝死综合症（SIDS）是工业化国家新生儿后死亡的主要原因通常它发生在睡眠期间——在无人目睹的情况下，它被推测发生在睡眠期间。本身，或在正常婴儿睡眠期间发生的许多睡眠和醒来之间的转变之一。今天的主要假说是唤醒缺陷假说：SIDS 或 SIDS 的一个子集，是由于上行唤醒网络（AAN）在关键发育时期的睡眠期间成为危及生命的压力源。唤醒被认为是意识的基本要素，也是恢复意识的必要条件。通过为重要过程提供兴奋性驱动，在呼吸和心血管挑战期间保持体内平衡 AAN 与调节大脑整合的皮质和皮质下网络相互连接。稳态反应，包括与脑干和边缘节点的连接。过去二十年提供的证据表明，血清素 (5-HT) 缺陷主要集中在脑干 AAN 中延髓头端网状结构的细胞学定义区域称之为假定的“SIDS 核心病变”(CLS) 在此 R01 应用中，我们建议测试两重。假设 CLS 的核心核彼此之间以及与一个或多个已知的 AAN 核位于脑干内部和上方，表明它们在解剖学上是脑干的一部分 AAN；SIDS 病例中血清素能 CLS 存在结构解剖异常与年龄匹配的尸检对照相比，我们将进行离体 MRI 扩散纤维束成像和前所未有的空间分辨率的光学相干断层扫描以及 5-HT 免疫细胞化学死后婴儿大脑从出生到生命结束后的第一年，即 SIDS 的风险期。通过将假定的核心 CLS 建立为不可分割的一部分，预计将产生重大的积极影响。 AAN涉及髓质5-HT神经元，它将为未来针对SIDS的大脑研究提供基础，让我们更接近 SIDS 的最终原因和具体的预防策略。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Longitudinal investigation of a xenograft tumor zebrafish model using polarization-sensitive optical coherence tomography.

使用偏振敏感光学相干断层扫描对异种移植肿瘤斑马鱼模型进行纵向研究。

DOI：
发表时间：
2022-09-13
期刊：
影响因子：
4.6
作者：
Lichtenegger, Antonia;Tamaoki, Junya;Licandro, Roxane;Mori, Tomoko;Mukherjee, Pradipta;Bian, Lixuan;Greutter, Lisa;Makita, Shuichi;Wöhrer, Adelheid;Matsusaka, Satoshi;Kobayashi, Makoto;Baumann, Bernhard;Yasuno, Yoshiaki
通讯作者：
Yasuno, Yoshiaki

Integration of imaging measurements at micro-, meso and macro-scale of the caudal medulla on a postmortem infant subject.

对死后婴儿受试者尾髓质的微观、中观和宏观尺度的成像测量进行整合。