CARE4Kids: Blood Biomarker Core

项目摘要/摘要-血液生物标记物核心 脑震荡每年影响近300万美国人(18岁以下多达190万人)，多达15- 30%伤后3个月未恢复。脑震荡的风险在早期和中期高出5倍。 青少年(EMA)比任何其他年龄组都高，强调有必要关注这一高危人群。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可能面临更高的长期症状和负担的风险 脑震荡后的缺陷。临床试验，以开发针对症状的疗法，以促进康复和 迫切需要预防急诊医生的长期残疾。为了优化未来的试验，准确的、前瞻性的 确定持续性脑震荡后症状的最高风险人群(PPCS；脑震荡后 症状持续3个月)以及谁将从预防性干预中受益是至关重要的。总目标 CARE4Kids的目的是识别和验证最敏感、最特异和最具可扩展性的生物标记物，以对PPCS进行分层 风险和识别潜在的内表型。这些生物标志物分为三大类：基于血液的， 神经成像和自主神经。血液生物标志物核心(BBC)将提供必要的资源和 收集、测量和分析一组反映关键的血液生物标志物(BBM)的技术专长 脑震荡后的生理性过程，包括轴突损伤、炎症、膜翻转、氧化 压力和神经传递的改变。具体目标1：英国广播公司将在技术上对 预期的血液生物标志物包括神经元/神经胶质蛋白、脂类、炎性细胞因子和神经肽 使用经过充分验证的分析方法的神经递质。数据质量将通过遵守 标准操作程序和对技术重现性的持续评估。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，以 确保所有研究地点的血液采集、存储和测量方案标准化， 包括1)使用美国国家神经疾病研究所和卒中研究所的相关公共数据元素 生物标记物的收集，2)研究人员的持续培训，以及3)持续的质量控制。具体目标3： BBC将与管理核心进行互动，并与成像生物标记核心和自主进行整合 确定BBM如何增强PPCS内表型的表征和改善的生物标记核心 PPCS预测的准确性通过1)表征与PPCS内表型相关的BBM特异性测量， 2)分析BBM数据。在本项目结束时，我们不仅将制定PPCS风险分层 实用、可扩展和准确的算法，我们将确定BBM对PPCS的独特贡献 急救人员。我们的结果有可能识别潜在的可改变的炎症途径，并阐明 这一年龄段症状恢复的生物学机制。

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.