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  • Review Article
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Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood

Nature Reviews Neurology volume 9, pages 201–210 (2013)Cite this article

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Abstract

Mild traumatic brain injury (TBI), which is defined as a head trauma resulting in a brief loss of consciousness and/or alteration of mental state, is usually benign, but occasionally causes persistent and sometimes progressive symptoms. Whether a threshold for the amount of brain injury and/or individual vulnerability might contribute to the development of these long-term consequences is unknown. Furthermore, reliable diagnostic methods that can establish whether a blow to the head has affected the brain (and in what way) are lacking. In this Review, we discuss potential biomarkers of injury to different structures and cell types in the CNS that can be detected in body fluids. We present arguments in support of the need for further development and validation of such biomarkers, and for their use in assessing patients with head trauma in whom the brain might have been affected. Specifically, we focus on the need for such biomarkers in the management of sports-related concussion, the most common cause of mild TBI in young individuals, to prevent long-term neurological sequelae due to concussive or subconcussive blows to the head.

Key Points

  • Biomarkers of neuronal, axonal and astroglial damage could be used to diagnose mild traumatic brain injury (TBI) and predict clinical outcomes of patients with head trauma

  • Such biomarkers could provide important information for medical counselling of at-risk individuals, such as military personnel and concussed athletes

  • Cerebrospinal fluid markers are preferred over peripheral blood markers, owing to their increased proximity to the brain and decreased susceptibility to the confounding effects of various extracerebral factors

  • Ultrasensitive assays are needed for reliable quantification of CNS-specific biomarkers in blood, as their concentrations are below the lower limit of detection by most standard immunoassays

  • Clinical studies of serial biomarker measurements in conjunction with advanced brain imaging during the acute and subacute phases of mild TBI are warranted

  • Longitudinal studies of biomarkers in patients with chronic or progressive symptoms after TBI might help to clarify the pathogenesis and clinical course of chronic traumatic encephalopathy

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Figure 1: Possible biomarkers of traumatic brain injury.

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Acknowledgements

The authors' research work is supported by the Swedish Research Council and Swedish State Support for Clinical Research (H. Zetterberg, K. Blennow), the Wolfson Foundation (H. Zetterberg) and NIH grants R01 NS038104, P01 NS056202 and R03 AG038911 (D. H. Smith).

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Authors and Affiliations

  1. Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, SE-431 80, Sweden

    Henrik Zetterberg & Kaj Blennow

  2. Department of Neurosurgery, Penn Medical Center for Brain Injury and Repair, University of Pennsylvania Medical Center, 105 Hayden Hall, 3320 Smith Walk, Philadelphia, 19104-6316, PA, USA

    Douglas H. Smith

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  1. Henrik Zetterberg
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H. Zetterberg wrote the article. H. Zetterberg, D. H. Smith and K. Blennow contributed equally to researching data for the article, discussion of the content, and review and editing of the manuscript before submission.

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Correspondence to Henrik Zetterberg.

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Zetterberg, H., Smith, D. & Blennow, K. Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood. Nat Rev Neurol 9, 201–210 (2013). https://doi.org/10.1038/nrneurol.2013.9

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