CARE4Kids: Blood Biomarker Core

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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.