The biological significance and clinical utility of emerging blood biomarkers for traumatic brain injury

HUIBREGTSE, M.E, Bazarian, J.J., Shultz, S.R., and Kawata K. The biological significance and clinical utility of emerging blood biomarkers for traumatic brain injury. NEUROSCI BIOBEHAV REV XX (130) XXX-XXX, 2021.Blood biomarkers can serve as objective measures to gauge traumatic brain injury (TBI) severity, identify patients at risk for adverse outcomes, and predict recovery duration, yet the clinical use of blood biomarkers for TBI is limited to a select few and only to rule out the need for CT scanning. The biomarkers often examined in neurotrauma research are proteomic markers, which can reflect a range of pathological processes such as cellular damage, astrogliosis, or neuroinflammation. However, proteomic blood biomarkers are vulnerable to degradation, resulting in short half-lives. Emerging biomarkers for TBI may reflect the complex genetic and neurometabolic alterations that occur following TBI that are not captured by proteomics, are less vulnerable to degradation, and are comprised of microRNA, extracellular vesicles, and neurometabolites. Therefore, this review aims to summarize our understanding of how biomarkers for brain injury escape the brain parenchymal space and appear in the bloodstream, update recent research findings in several proteomic biomarkers, and characterize biological significance and examine clinical utility of microRNA, extracellular vesicles, and neurometabolites.