Abstract
Traumatic brain injury (TBI) imposes a significant economic and social burden. The diagnosis and prognosis of mild TBI, also called concussion, is challenging. Concussions are common among contact sport athletes. After a blow to the head, it is often difficult to determine who has had a concussion, who should be withheld from play, if a concussed athlete is ready to return to the field, and which concussed athlete will develop a post-concussion syndrome. Biomarkers can be detected in the cerebrospinal fluid and blood after traumatic brain injury and their levels may have prognostic value. Despite significant investigation, questions remain as to the trajectories of blood biomarker levels over time after mild TBI. Modeling the kinetic behavior of these biomarkers could be informative. We propose a one-compartment kinetic model for S100B, UCH-L1, NF-L, GFAP, and tau biomarker levels after mild TBI based on accepted pharmacokinetic models for oral drug absorption. We approximated model parameters using previously published studies. Since parameter estimates were approximate, we did uncertainty and sensitivity analyses. Using estimated kinetic parameters for each biomarker, we applied the model to an available post-concussion biomarker dataset of UCH-L1, GFAP, tau, and NF-L biomarkers levels. We have demonstrated the feasibility of modeling blood biomarker levels after mild TBI with a one compartment kinetic model. More work is needed to better establish model parameters and to understand the implications of the model for diagnostic use of these blood biomarkers for mild TBI.
Recommended Citation
S. Azizi et al., "A Kinetic Model for Blood Biomarker Levels after Mild Traumatic Brain Injury," Frontiers in Neurology, vol. 12, article no. 668606, Frontiers Media, Jul 2021.
The definitive version is available at https://doi.org/10.3389/fneur.2021.668606
Department(s)
Mathematics and Statistics
Second Department
Biological Sciences
Third Department
Electrical and Computer Engineering
Research Center/Lab(s)
Center for High Performance Computing Research
Second Research Center/Lab
Intelligent Systems Center
Keywords and Phrases
Blood Biomarkers; Concussion; Kinetics; Mathematical Modeling; Mild Traumatic Brain Injury; Sensitivity Analysis; Uncertainty Analysis
International Standard Serial Number (ISSN)
1664-2295
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2021 The Authors, All rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution 4.0 License.
Publication Date
06 Jul 2021
Included in
Applied Statistics Commons, Biochemistry Commons, Biology Commons, Computer Engineering Commons, Trauma 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.