CARE4Kids: Blood Biomarker Core

CARE4Kids：血液生物标志物核心

• 批准号: 10203602
• 负责人: JEFFREY John BAZARIAN
• 金额: $ 48.86万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-08 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10203602
• 关键词: Acute; Adolescence; Adolescent; Affect; Age; Algorithms; American; Biochemical; Biological; Biological Markers; Blood; Blood specimen; Brain; Brain Concussion; Caring; Categories; Clinical; Clinical Management; Clinical Treatment; Clinical Trials; Collection; Common Data Element; Data; Development; Dizziness; Early identification; Ensure; Evaluation; Future; Goals; Headache; Human Resources; Image; Inflammation; Inflammatory; Injury; Intervention; Lipids; Measurement; Measures; Membrane; Memory; Methods; Mission; Molecular; Monitor; National Institute of Neurological Disorders and Stroke; Neurons; Neuropeptides; Neurotransmitters; Oxidative Stress; Pathway interactions; Peptides; Phenotype; Physiological; Physiological Processes; Populations at Risk; Post-Concussion Syndrome; Procedures; Process; Protein Analysis; Proteins; Protocols documentation; Psychophysiology; Publishing; Quality Control; Radiology Specialty; Recovery; Reporting; Reproducibility; Research Personnel; Research Project Grants; Resources; Risk; Schools; Site; Standardization; Symptoms; Technical Expertise; Techniques; Time; Training; Work; Youth; age group; axon injury; base; biobank; blood-based biomarker; cognitive function; critical period; cytokine; data quality; design; disability; emotional functioning; endophenotype; executive function; experience; falls; genetic analysis; high risk; imaging biomarker; improved; medical specialties; neurodevelopment; neuroimaging; neurotransmission; novel; peripheral blood; prediction algorithm; prevent; preventive intervention; prospective; repository; risk stratification; sample collection; social; specific biomarkers; success; targeted treatment; trait; white matter change; young adult

PROJECT SUMMARY/ABSTRACT – Blood Biomarker Core Concussions affect nearly 3 million Americans annually (up to 1.9 million under the age of 18), with up to 15- 30% not recovered 3 months after injury. The risk of concussion is 5 times higher among early and middle adolescents (EMA) than any other age group, highlighting the need to focus on this at-risk population. Because early and middle adolescence is a critical period for neurodevelopment processes required for optimal cognitive, emotional, and executive functioning, EMAs may be at increased risk for the burden of long-term symptoms and deficits after concussion. Clinical trials to develop symptom-targeted therapies to facilitate recovery and to prevent long-term disability among EMAs are urgently needed. To optimize future trials, an accurate, prospective identification of those at the greatest risk for persistent post-concussive symptoms (PPCS; post-concussive symptoms lasting >3 months) and who would benefit from preventive interventions is essential. The overall goal of CARE4Kids is to identify and validate the most sensitive, specific, and scalable biomarkers to stratify PPCS risk and identify underlying endophenotypes. These biomarkers fall into 3 broad categories: blood-based, neuroimaging, and autonomic. The Blood Biomarker Core (BBC) will provide the necessary resources and technical expertise to collect, measure and analyze a panel of blood-based biomarkers (BBMs) reflecting key physiologic post-concussion processes, including axonal injury, inflammation, membrane turnover, oxidative stress and altered neurotransmission. Specific Aim 1: The BBC will make technically robust measurements of prospective blood biomarkers including neuronal/glial proteins, lipids, inflammatory cytokines, and neuropeptide neurotransmitters using well-validated analytic approaches. Data quality will be assured by compliance with standard operating procedures and continuous evaluation of technical reproducibility. Data will be reported to the Data Coordinating Core (DCC). Specific Aim 2: The BBC will work closely with BioSEND and the DCC to ensure that blood collection, storage, and measurement protocols are standardized across all study sites, including 1) the use of National Institute of Neurological Disorders and Stroke Common Data Elements related to biomarker collection, 2) ongoing training of study personnel, and 3) ongoing quality control. Specific Aim 3: The BBC will interact with the Administrative Core and integrate with the Imaging Biomarker Core and Autonomic Biomarker Core to determine how BBMs may enhance characterization of PPCS endophenotypes and improve accuracy of PPCS prediction by 1) characterizing BBM-specific measures in relation to PPCS endophenotypes, and 2) analyzing BBM data. At the conclusion of this project, we will not only develop a PPCS risk stratification algorithm that is practical, scalable, and accurate, we will identify the unique contribution of BBMs to PPCS in EMAs. Our results have potential to identify potentially modifiable inflammatory pathways and to elucidate the biologic mechanism underlying symptomatic recovery in this age group.

项目总结/摘要-血液生物标志物核心 脑震荡每年影响近300万美国人（18岁以下高达190万），其中15- 30%伤后3个月仍未恢复。脑震荡的风险在早期和中期高出5倍 青少年（EMA）比任何其他年龄组，强调需要关注这一风险人群。因为 青春期早期和中期是最佳认知所需的神经发育过程的关键时期， 情绪和执行功能，EMA可能会增加长期症状负担的风险， 脑震荡后的缺陷临床试验，以开发靶向治疗，以促进恢复， 预防EMAs中的长期残疾是当务之急。为了优化未来的试验， 识别持续性脑震荡后症状（PPCS;脑震荡后 症状持续时间>3个月）以及谁将从预防性干预措施中受益至关重要。总目标 CARE 4Kids的目标是识别和验证最敏感、特异和可扩展的生物标志物，以分层PPCS 风险和识别潜在的内在表型。这些生物标志物分为3大类：基于血液的， 神经成像和自主神经血液生物标志物核心（BBC）将提供必要的资源， 收集、测量和分析一组血液生物标志物（BBM）的技术专长， 生理性脑震荡后过程，包括轴突损伤、炎症、膜更新、氧化损伤、神经元损伤和神经元损伤。 压力和改变的神经传递具体目标1：英国广播公司将在技术上对 前瞻性血液生物标志物，包括神经元/神经胶质蛋白、脂质、炎性细胞因子和神经肽 神经递质使用经过验证的分析方法。数据质量将通过遵守 标准操作规程和技术再现性的持续评估。数据将报告给 数据协调核心（DCC）。具体目标2：BBC将与BioSEND和DCC密切合作， 确保所有研究中心的血液采集、储存和测量方案标准化， 包括1）使用国家神经疾病和卒中研究所的相关通用数据元素 生物标志物收集，2）研究人员的持续培训，和3）持续的质量控制。具体目标3： BBC将与管理核心互动，并与成像生物标志物核心和自主神经系统整合。 生物标志物核心，以确定BBM如何增强PPCS内在表型的表征并改善 通过1）表征与PPCS内在表型相关的BBM特异性测量， （2）BBM数据分析。在本项目结束时，我们不仅将制定PPCS风险分层， 算法是实用的，可扩展的，准确的，我们将确定BBM对PPCS的独特贡献， EMA。我们的结果有可能识别潜在的可改变的炎症途径并阐明炎症反应的机制。 该年龄组症状恢复的生物学机制。