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Mass Spectrometry-Based Approaches for Clinical Biomarker Discovery in Traumatic Brain Injury


Purpose of Review

Precision treatments to address the multifaceted pathophysiology of traumatic brain injury (TBI) are desperately needed, which has led to the intense study of fluid-based protein biomarkers in TBI. Mass Spectrometry (MS) is increasingly being applied to biomarker discovery and quantification in neurological disease to explore the proteome, allowing for more flexibility in biomarker discovery than commonly encountered antibody-based assays. In this narrative review, we will provide specific examples of how MS technology has advanced translational research in traumatic brain injury (TBI) focusing on clinical studies, and looking ahead to promising emerging applications of MS to the field of Neurocritical Care.

Recent Findings

Proteomic biomarker discovery using MS technology in human subjects has included the full range of injury severity in TBI, though critically ill patients can offer more options to biofluids given the need for invasive monitoring. Blood, urine, cerebrospinal fluid, brain specimens, and cerebral extracellular fluid have all been sources for analysis. Emerging evidence suggests there are distinct proteomic profiles in radiographic TBI subtypes, and that biomarkers may be used to distinguish patients sustaining TBI from healthy controls. Metabolomics may offer a window into the perturbations of ongoing cerebral insults in critically ill patients after severe TBI.


Emerging MS technologies may offer biomarker discovery and validation opportunities not afforded by conventional means due to its ability to handle the complexities associated with the proteome. While MS techniques are relatively early in development in the neurosciences space, the potential applications to TBI and neurocritical care are likely to accelerate in the coming decade.

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The authors wish to thank Dr. Shraddha Mainali for reviewing their paper. Work was performed in the Environmental Molecular Sciences Laboratory, a US Department of Energy Office of Biological and Environmental Research national scientific user facility located at Pacific Northwest National Laboratory in Richland, Washington. Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy under Contract No. DE-AC05-76RLO 1830.


Research reported in this publication was supported by the National Institute Of Neurological Disorders And Stroke of the National Institutes of Health under Award Number K23NS110828. Portions of this research were also supported by NIH NIGMS GM103493.

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Correspondence to H. E. Hinson MD, MCR.

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Creech, M., Carvalho, L., McCoy, H. et al. Mass Spectrometry-Based Approaches for Clinical Biomarker Discovery in Traumatic Brain Injury. Curr Treat Options Neurol (2022).

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  • Traumatic brain injury
  • Proteomics
  • Biomarker
  • Mass spectrometry