A link between sleep-wake disturbances and enlarged perivascular spaces in youth with traumatic brain injury

患有创伤性脑损伤的青少年睡眠-觉醒障碍与血管周围间隙扩大之间的联系

• 批准号: 10368063
• 负责人: Juan Andres Piantino
• 金额: $ 16.54万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10368063
• 关键词: 18 year old; Accident and Emergency department; Accounting; Active Learning; Acute; Address; Affect; Age; Alzheimer' s Disease; Animal Model; Animals; Anxiety; Appearance; Award; Biological; Biometry; Brain; Brain Concussion; Caring; Cerebrum; Child; Childhood; Clinical; Confusion; Contrast Media; Control Groups; Data; Data Analyses; Development; Devices; Emergency research; Enrollment; Equipment and supply inventories; Excision; Experimental Models; Fatigue; Fellowship; Foundations; Functional disorder; Future; Goals; Headache; Health Sciences; Human; Image; Impaired cognition; Impairment; Injury; Intervention; Intrathecal Injections; K-Series Research Career Programs; Knowledge; Link; Long-Term Effects; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Mediator of activation protein; Memory impairment; Mental Depression; Mentors; Methods; Minor; Modeling; Moods; Morbidity - disease rate; Mycobacterium tuberculosis; Normal Pressure Hydrocephalus; Oregon; Orthopedics; Outcome; Outcome Study; Pathology; Patients; Pediatric Neurology; Play; Population; Positioning Attribute; Post-Concussion Syndrome; Procedures; Publishing; Recording of previous events; Recovery; Reporting; Research; Research Personnel; Research Training; Residencies; Rodent Model; Role; Sleep; Sleep Disorders; Sleep disturbances; Symptoms; Techniques; Testing; Therapeutic Intervention; Training; Training Programs; Traumatic Brain Injury; United States; Universities; Vascular Dementia; Work; Youth; actigraphy; age group; base; brain magnetic resonance imaging; career; cohort; design; follow-up; glymphatic dysfunction; glymphatic function; glymphatic system; image processing; insight; interstitial; longitudinal analysis; meetings; mild traumatic brain injury; neurophysiology; new technology; novel; prevent; professor; risk stratification; skills; sleep pattern; sleep quality; solute; tool; wasting

Project Summary: I propose a 5-year mentored research training program to become a leader in the field of pediatric sleep research. I am residency-trained in Child Neurology, and dual fellowship-trained in Pediatric Neurocritical Care, and Clinical Neurophysiology. I am currently Assistant Professor of Child Neurology at Oregon Health and Science University. This proposal focuses specifically on understanding the role of sleep as a mediator of recovery in youth with mild TBI (mTBI), and the biological mechanisms underlying this mediator effect. My career plan will provide me advanced quantitative skills in biostatistical modeling and longitudinal analysis, use of actigraphy in sleep research, and advanced imaging processing. The training will come through formal coursework, mentored research, experiential learning, and scientific meetings. The overall objective of this proposal is to establish the mechanisms linking sleep-wake disturbances (SWD), glymphatic pathway disturbances, and persistent post-concussive symptoms in youth with mTBI. Every year, millions of youth are affected by mTBI. Post-concussive symptoms include headaches, fatigue, irritability, confusion, forgetfulness, and mood problems. Sleep problems are also a common complaint in this population. Patients with mTBI and subjective sleep problems report more prolonged post-concussive symptoms. However, despite this knowledge, several questions remain: 1) In youth with acute mTBI, to what extent do sleep disturbances play a mediating role in the persistence of post-concussive symptoms? 2) What are the biological mechanisms underlying this mediator effect? In order to answer these questions, I have decided to study the glymphatic pathway, a network of perivascular spaces that supports the clearance of interstitial solutes and wastes from the brain during sleep. Recently, the presence of enlarged perivascular spaces (ePVS) seen on brain MRI has been proposed as a noninvasive marker of glymphatic pathway dysfunction. Our preliminary data and findings from other investigators suggest that enlarged ePVS are seen in patients with mTBI, particularly in those with sleep disturbances. We will take advantage of novel technology developed at OHSU to measure ePVS in a cohort of youth with mTBI. The central hypothesis of this proposal is that glymphatic pathway dysfunction resulting from SWD drives the development and persistence of post-concussive symptoms. To test this hypothesis we will 1) Define the role of SWD as a mediator of persistent post-concussive symptoms in youth with mTBI; 2) Determine the combined effect of mTBI and SWD on ePVS burden in youth and the relationship between ePVS burden and persistent post- concussive symptoms. This research will help understand how sleep affects recovery after mTBI, and the mechanisms underlying this mediator effect. Data generated through this work will allow the design of larger longitudinal studies aimed at defining the long-term effects of SWD on outcomes after mTBI. It will also encourage the exploration of novel mechanisms affecting recovery in animal models of TBI.

项目摘要： 我建议一项为期5年的指导研究培训计划，以成为小儿睡眠领域的领导者 研究。我接受了儿童神经病学的居住训练，并在儿科神经关怀中接受了双重研究金的培训， 和临床神经生理学。我目前是俄勒冈州健康儿童神经病学助理教授 科学大学。该提案专门针对理解睡眠作为调解人的作用 轻度TBI（MTBI）青年的恢复以及这种介体效应的生物学机制。我的 职业计划将为我提供生物统计建模和纵向分析的高级定量技能，使用 睡眠研究和高级成像处理中的动作法。培训将通过正式 课程工作，指导的研究，体验式学习和科学会议。 该提案的总体目的是建立连接睡眠障碍的机制 （SWD），肾小球途径障碍和年轻人持续的脑震荡症状 mtbi。每年，数百万年轻人都受到MTBI的影响。脑后症状包括头痛， 疲劳，烦躁，混乱，健忘和情绪问题。睡眠问题也是常见的投诉 在这个人群中。 MTBI和主观睡眠问题的患者报告了更长时间的脑震荡 症状。但是，尽管知识仍然存在一些问题：1）在急性mtbi的青年中 睡眠障碍在脑震荡症状的持久性中起着中介作用？ 2）什么 这种介体效应的生物学机制是否存在？为了回答这些问题，我有 决定研究Glymphatic途径，这是一个支持清除率的周围空间网络 睡眠期间，大脑的间质溶质和废物。最近，血管周围的存在 在脑MRI上看到的空间（EPV）已被提议作为胶状途径的无创标记 功能障碍。我们的初步数据和其他研究人员的发现表明，在 MTBI的患者，特别是在患有睡眠障碍的患者中。我们将利用新技术 在OHSU开发以测量MTBI青年队列中的EPV。中心假设 提案是SWD引起的开发和 脑震荡症状的持久性。为了检验这一假设，我们将1）将SWD的作用定义为 MTBI青年持续脑震荡症状的介体； 2）确定 MTBI和SWD对年轻人的EPVS负担以及EPVS负担与持续存在的关系之间的关系 脑震荡症状。这项研究将有助于了解睡眠如何影响MTBI之后的康复，以及 这种介体效应的机制。通过这项工作生成的数据将允许设计较大 纵向研究旨在定义SWD对MTBI后结果的长期影响。它也会 鼓励探索影响TBI动物模型恢复的新机制。