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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：
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
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/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

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期婴儿死亡的主要原因