Title: Novel biomarkers within extracellular vesicles for the identification of traumatic brain injury severity.
Authors: Tony Zifeng Tang1,4, Yingxin Zhao1, Stefan H. Bossmann2, Massoud Motamedi1, Bartosz Szczesny1,3, *
Departments of 1Ophthalmology and Visual Sciences, 3Anesthesiology, 4Neuroscience Graduate Program, University of Texas Medical Branch, Galveston, TX, USA; 2Department of Cancer Biology, The University of Kansas Medical Center, Kansas City, KS, USA
Abstract body: In 2019, it was estimated that roughly 155 people died each day from traumatic brain injury (TBI) related effects in the United States. The current diagnosis of TBI include a neurological exam such as Glasgow Coma Scale (GCS) and imaging tests (CT, MRI) both of which are time consuming and require dedicated resources that may not be readily available in resource-challenged environments such as rural emergency rooms, sports arenas, and battlefields. Thus, there is an urgent need for the rapid identification of novel biomarkers in liquid biopsies for an early detection and quantitative monitoring of TBI severity. Based on our preliminary data and recently published study, we propose that amounts of circulating cell free DNA (ccf-DNA) particularly of mitochondrial origin and brain-type specific markers, present in circulating extracellular vesicles (EV’s), represent a novel class of biomarkers for TBI. In this project, we subjected 8–10-week-old C57BL6 male mice to mild TBI using the closed head weight drop model followed by isolation of blood plasma at several time points post injury. We have characterized the number and size distribution of EV’s post injury, together with the origin and amount of ccf-DNA released in the EV’s. Furthermore, we have performed proteomic analysis of isolated EVs and discovered several novel protein biomarkers that are both up- and downregulated across various time points post-injury. Our findings suggest ccf-DNA, along with EVs’ biomarkers, could potentially be used as diagnostic tools for the rapid, accurate assessment of TBI occurrence and severity.
Keywords: biomarker, concussion/mTBI, diagnostics, blood brain barrier, neurocritical care.
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