An update on diagnostic and prognostic biomarkers for traumatic brain injury

Kevin K Wang, Zhihui Yang, Tian Zhu, Yuan Shi, Richard Rubenstein, J Adrian Tyndall, Geoff T Manley, Kevin K Wang, Zhihui Yang, Tian Zhu, Yuan Shi, Richard Rubenstein, J Adrian Tyndall, Geoff T Manley

Abstract

Traumatic brain injury (TBI) is a major worldwide neurological disorder of epidemic proportions. To date, there are still no FDA-approved therapies to treat any forms of TBI. Encouragingly, there are emerging data showing that biofluid-based TBI biomarker tests have the potential to diagnose the presence of TBI of different severities including concussion, and to predict outcome. Areas covered: The authors provide an update on the current knowledge of TBI biomarkers, including protein biomarkers for neuronal cell body injury (UCH-L1, NSE), astroglial injury (GFAP, S100B), neuronal cell death (αII-spectrin breakdown products), axonal injury (NF proteins), white matter injury (MBP), post-injury neurodegeneration (total Tau and phospho-Tau), post-injury autoimmune response (brain antigen-targeting autoantibodies), and other emerging non-protein biomarkers. The authors discuss biomarker evidence in TBI diagnosis, outcome prognosis and possible identification of post-TBI neurodegernative diseases (e.g. chronic traumatic encephalopathy and Alzheimer's disease), and as theranostic tools in pre-clinical and clinical settings. Expert commentary: A spectrum of biomarkers is now at or near the stage of formal clinical validation of their diagnostic and prognostic utilities in the management of TBI of varied severities including concussions. TBI biomarkers could serve as a theranostic tool in facilitating drug development and treatment monitoring.

Keywords: Biomarkers; diagnostics; neurotrauma; theranostics; traumatic brain injury.

Figures

Figure 1.. Graphic representation of major TBI…
Figure 1.. Graphic representation of major TBI protein biomarkers linked to different pathophysiologic processes in TBI.
These processes thus far include axonal injury, dendritic injury, neuronal cell body injury, demyelination, synaptic injury and astroglia injury and microglia responses. Cellular and subcellular localization of representative TBI biomarkers are also shown with immunocytochemical staining images (based on mouse brain data).
Figure 2.. A continuum of protein biomarkers…
Figure 2.. A continuum of protein biomarkers in tracking different phases of TBI.
Acute neuronal cell body injury markers UCH-L1 (ubiquitin C-terminal hydrolase-L1), NSE (neuronal specific enolase), necrosis markers SBDP150/145 (αII-spectrin breakdown product 150 kDa & 145 kDa), SNTF (αII-spectrin N-terminal fragment), S100B (glial calcium-binding protein S100B), GFAP & BDP (glial fibrillary acidic protein & breakdown product), delayed axonal injury NF-H, M, L (neurofilament-heavy, medium & light), demyelination marker MBP (myelin basic protein), apoptosis marker SBDP120 (αII-spectrin breakdown product 120 kDa), autoimmunity markers auto[GFAP] (autoantibodies to GFAP), neurodegeneration markers Tau (tau protein), P-Tau (phosphorylated tau), Aβ (amyloid β-peptides) and TDP-43.

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