Abstract
Background: The use of blood biomarkers after mild traumatic brain injury (mTBI) has been widely studied. We have identified eight unresolved issues related to the use of five commonly investigated blood biomarkers: neurofilament light chain, ubiquitin carboxy-terminal hydrolase-L1, tau, S100B, and glial acidic fibrillary protein. We conducted a focused literature review of unresolved issues in three areas: mode of entry into and exit from the blood, kinetics of blood biomarkers in the blood, and predictive capacity of the blood biomarkers after mTBI.
Findings: Although a disruption of the blood brain barrier has been demonstrated in mild and severe traumatic brain injury, biomarkers can enter the blood through pathways that do not require a breach in this barrier. A definitive accounting for the pathways that biomarkers follow from the brain to the blood after mTBI has not been performed. Although preliminary investigations of blood biomarkers kinetics after TBI are available, our current knowledge is incomplete and definitive studies are needed. Optimal sampling times for biomarkers after mTBI have not been established. Kinetic models of blood biomarkers can be informative, but more precise estimates of kinetic parameters are needed. Confounding factors for blood biomarker levels have been identified, but corrections for these factors are not routinely made. Little evidence has emerged to date to suggest that blood biomarker levels correlate with clinical measures of mTBI severity. The significance of elevated biomarker levels thirty or more days following mTBI is uncertain. Blood biomarkers have shown a modest but not definitive ability to distinguish concussed from non-concussed subjects, to detect sub-concussive hits to the head, and to predict recovery from mTBI. Blood biomarkers have performed best at distinguishing CT scan positive from CT scan negative subjects after mTBI.
Recommended Citation
D. B. Hier et al., "Blood Biomarkers for Mild Traumatic Brain Injury: A Selective Review of Unresolved Issues," Biomarker Research, vol. 9, no. 1, article no. 70, BioMed Central, Sep 2021.
The definitive version is available at https://doi.org/10.1186/s40364-021-00325-5
Department(s)
Biological Sciences
Second Department
Mathematics and Statistics
Third Department
Electrical and Computer Engineering
Research Center/Lab(s)
Intelligent Systems Center
Keywords and Phrases
Blood biomarkers; Concussion; CT scan; GFAP; Kinetics; Mild traumatic brain injury; NF-L; Return to sport; S100B; Tau; UCH-L1
International Standard Serial Number (ISSN)
2050-7771
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2021 Authors, All rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution 4.0 License.
Publication Date
16 Sep 2021
Included in
Biology Commons, Electrical and Computer Engineering Commons, Statistics and Probability Commons
Comments
Research was partially sponsored by the Mary K. Finley Missouri Endowment, the Missouri S&T Intelligent Systems Center, the National Science Foundation and the Leonard Wood Institute in cooperation with the U.S. Army Research Laboratory and was accomplished under Cooperative Agreement Number W911NF-14-2-0034. Additional support came from NIH Award R15 GM117507-01A1.