title: Blood biomarkers for brain injury: What are we measuring?
abstract: Accurate diagnosis for mild traumatic brain injury (mTBI) remains challenging, as prognosis and return-to-play/work decisions are based largely on patient reports. Numerous investigations have identified and characterized cellular factors in the blood as potential biomarkers for TBI, in the hope that these factors may be used to gauge the severity of brain injury. None of these potential biomarkers have advanced to use in the clinical setting. Some of the most extensively studied blood biomarkers for TBI include S100β, neuron-specific enolase, glial fibrillary acidic protein, and Tau. Understanding the biological function of each of these factors may be imperative to achieve progress in the field. We address the basic question: what are we measuring? This review will discuss blood biomarkers in terms of cellular origin, normal and pathological function, and possible reasons for increased blood levels. Considerations in the selection, evaluation, and validation of potential biomarkers will also be addressed, along with mechanisms that allow brain-derived proteins to enter the bloodstream after TBI. Lastly, we will highlight perspectives and implications for repetitive neurotrauma in the field of blood biomarkers for brain injury.
authors.affiliation: Department of Kinesiology, Temple University, Philadelphia, PA, USA; Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA, USA. Electronic address: keisuke.kawata@temple.edu.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kawata
authors.affiliation: Department of Neurological Surgery, Keck School of Medicine, University of Southern California, 1520 San Pablo St. #3800, Los Angeles, CA 90033, USA. Electronic address: chasliu@cheme.caltech.edu.
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA. Electronic address: tue39636@temple.edu.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Merkel
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA. Electronic address: servio@temple.edu.
authors.forename: Servio H
authors.initials: SH
authors.lastname: Ramirez
authors.affiliation: Department of Kinesiology, Temple University, Philadelphia, PA, USA. Electronic address: rtierney@temple.edu.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Tierney
authors.affiliation: Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA, USA. Electronic address: tdl@temple.edu.
authors.forename: Dianne
authors.initials: D
authors.lastname: Langford
mesh_terms: D015415:Biomarkers; D001930:Brain Injuries; D005904:Glial Fibrillary Acidic Protein; D006801:Humans; D064568:S100 Calcium Binding Protein beta Subunit
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D064568:S100 Calcium Binding Protein beta Subunit
keywords: Blood biomarker; Blood-brain barrier; Concussion; Mild TBI