Prognostic biomarkers of recovery from traumatic brain injury: assessment of effectiveness and prospects of application

A literature review was conducted on biomarkers, such as proteins, metabolites and other biological molecules found in biological fluids, as a tool that can improve the understanding of pathophysiological processes in traumatic brain injury (TBI) and contribute to the development of promising therapeutic approaches. The results of the systematic review show that biomarkers have significant potential for clinical application, but further standardization of technologies for their detection and analysis is required. The development of new platforms, such as POC systems using electrochemical biosensors, can provide fast and reliable diagnosis at all stages of TBI treatment. For further in-depth study, it is necessary to combine the efforts of the interdisciplinary research community, which will create personalized treatment strategies and improve long-term outcomes for patients.

1. Biomarkers of brain damage in children with traumatic brain injury / V.G. Pinelis, E.G. Sorokina, Zh.B. Semenova, [et. al.] // Journal of Neurology and Psychiatry named after S.S. Korsakov. 2015; 115(8): 66-72.

2. Zudova A.I., Suhorosova A.G., Solomatina L.V. Traumatic brain injury and neuroinflammation: a review of key biomarkers // Acta Biomedica Scientifica. 2020; 5(5): 60-67.

3. Mild traumatic brain injury | Abbott for Central Laboratories. https://www.corelaboratory.abbott/int/ru/offerings/segments/neurology/mild-traumatic-brain-injury.html?utm_source=chatgpt.com

4. Basic principles of microdialysis of the brain and modern applications in experimental neurobiology and neurochemistry / E.V. Haritonova, O.L. Lopatina, S.A. Marchenko, [et. al.] // Fundamental and Clinical Medicine. 2020; 5(3): 85-97.

5. Evaluation of potential biomarkers of cellular brain damage in mild traumatic brain injuries / Kovtun N.A., Savelyeva M.I., Trofimenko A.V., [et. al.] Kremlin Medicine. Clinical Bulletin. 2020; 4: 34-46. – DOI: 10.26269/00k8-t921. – EDN PESFLZ.

6. Khrapov Ju.V., Poroisky S.V. The role of brain substance damage biomarkers in the diagnosis, assessment of treatment efficacy, and prediction of outcomes in severe traumatic brain injury. // Volgograd Scientific Medical Journal. 2013; 3: 10-20.

7. Abdul-Muneer P.M., Chandra N., Haorah J. Interactions of oxidative stress and neurovascular inflammation in the pathogenesis of traumatic brain injury. Mol Neurobiol. 2015. Vol. 51, No. 3. P. 966-979. doi: 10.1007/s12035-014-8752-3. Epub 2014 May 28. PMID: 24865512; PMCID: PMC9420084.

8. Diaz-Arrastia R, Wang K.K., Papa L, et al. Acute biomarkers of traumatic brain injury: relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein. TRACK-TBI Investigators. J Neurotrauma. 2014. Vol. 31, No. 1. P. 19-25. doi: 10.1089/neu.2013.3040. Epub 2013 Oct 9. PMID: 23865516; PMCID: PMC3880090.

9. Arun P., Abu-Taleb R., Oguntayo S., et al. Acute mitochondrial dysfunction after blast exposure: potential role of mitochondrial glutamate oxaloacetate transaminase. J Neurotrauma. 2013. Vol. 30, No. 19. P. 1645-1651. doi: 10.1089/neu.2012.2834. Epub 2013 Aug 9. PMID: 23600763.

10. Atif H., Hicks S.D. A Review of MicroRNA Biomarkers in Traumatic Brain Injury. J Exp Neurosci. 2019. Vol. 13. Article 1179069519832286. doi: 10.1177/1179069519832286. PMID: 30886525; PMCID: PMC6410383.

11. Bakay R.A., Sweeney K.M., Wood J.H. Pathophysiology of cerebrospinal fluid in head injury: Part 2. Biochemical markers for central nervous system trauma. Neurosurgery. 1986. Vol. 18, No. 3. P. 376-382. doi: 10.1227/00006123-198603000-00026. PMID: 3010171.

12. Bakay R.A., Ward Jr. A.A. Enzymatic changes in serum and cerebrospinal fluid in neurological injury. J Neurosurg. 1983. Vol. 58, No. 1. P. 27-37. doi: 10.3171/jns.1983.58.1.0027. PMID: 6847906.

13. Mrozek S, Dumurgier J, Citerio G, et al. Biomarkers and acute brain injuries: interest and limits. Crit Care. 2014. Vol. 18(2). P. 220. doi: 10.1186/cc13841. PMID: 25029344; PMCID: PMC4056618.

14. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Biomarkers Definitions Working Group. Clin Pharmacol Ther. 2001. Vol. 69, No. 3. P. 89-95. doi: 10.1067/mcp.2001.113989. PMID: 11240971.

15. Papa L., Robertson C.S., Wang K.K., et al. Biomarkers improve clinical outcome predictors of mortality following non-penetrating severe traumatic brain injury. Neurocrit Care. 2015. Vol. 22, No. 1. P. 52-64. doi: 10.1007/s12028-014-0028-2. PMID: 25052159.

16. Visser K., Koggel M., Blaauw J., et al. Blood-based biomarkers of inflammation in mild traumatic brain injury: A systematic review. Neurosci Biobehav Rev. 2022. Vol. 132. P. 154-168. doi: 10.1016/j.neubiorev.2021.11.036.

17. Alluri H., Wiggins-Dohlvik K., Davis M.L., et al. Blood-brain barrier dysfunction following traumatic brain injury. Metab Brain Dis. 2015. Vol. 30, No. 5. P. 1093-1104. doi: 10.1007/s11011-015-9651-7. Epub 2015 Jan 28. PMID: 25624154.

18. Capizzi A., Woo J., Verduzco-Gutierrez M. Traumatic Brain Injury: An Overview of Epidemiology, Pathophysiology, and Medical Management. Med Clin North Am. 2020. Vol. 104, No. 2. P. 213-238. doi: 10.1016/j.mcna.2019.11.001. PMID: 32035565.

19. Mercier E, Tardif P.A., Emond M, et al. Characteristics of patients included and enrolled in studies on the prognostic value of serum biomarkers for prediction of postconcussion symptoms following a mild traumatic brain injury: a systematic review. BMJ Open. 2017. Vol. 7. Article e017848. doi: 10.1136/bmjopen-2017-017848.

20. Lagerstedt L., Egea-Guerrero J.J., Bustamante A., et al. Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury. PLoS One. 2018. Vol. 13, No. 7. Article e0200394. doi: 10.1371/journal.pone.0200394. PMID: 29985933; PMCID: PMC6037378.

21. Stenberg M, Koskinen L.D., Jonasson P., et al. Computed tomography and clinical outcome in patients with severe traumatic brain injury. Brain Inj. 2017. Vol. 31, No. 3. P. 351-358. doi: 10.1080/02699052.2016.1261303. Epub 2017 Feb 16. PMID: 28296529.

22. Kaste M, Hernesniemi J., Somer H., et al. Creatine kinase isoenzymes in acute brain injury. J Neurosurg. 1981. Vol. 55, No. 4. P. 511-515. doi: 10.3171/jns.1981.55.4.0511. PMID: 7276998.

23. Kellermann I., Kleindienst A., Hore N., et al. Early CSF and Serum S100B Concentrations for Outcome Prediction in Traumatic Brain Injury and Subarachnoid Hemorrhage. Clin Neurol Neurosurg. 2016. Vol. 145. P. 79-83. doi: 10.1016/j.clineuro.2016.04.005. Epub 2016 Apr 8. PMID: 27101088.

24. Dewan M.C., Rattani A., Gupta S, et al. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2018. Vol. 130, No. 4. P. 1080-1097. doi: 10.3171/2017.10.JNS17352. PMID: 29701556.

25. Lööv C., Nadadhur A.G., Hillered L., et al. Extracellular ezrin: a novel biomarker for traumatic brain injury. J Neurotrauma. 2015. Vol. 32(4). P. 244-51. doi: 10.1089/neu.2014.3517. Epub 2014 Nov 24. PMID: 25087457.

26. Beard K., Yang Z., Haber M., et al. Extracellular vesicles as distinct biomarker reservoirs for mild traumatic brain injury diagnosis. Brain Commun. 2021. Vol. 3. Article fcab151. doi: 10.1093/braincomms/fcab151.

27. Mondello S., Thelin E.P., Shaw G., et al. Extracellular vesicles: pathogenetic, diagnostic and therapeutic value in traumatic brain injury. Expert Rev Proteomics. 2018. Vol. 15(5). P. 451-461. doi: 10.1080/14789450.2018.1464914. Epub 2018 Apr 25. PMID: 29671356.

28. Shakir M., Altaf A., Irshad H.A., et al. Factors delaying the continuum of care for the management of traumatic brain injury in lowand middle-income countries: a systematic review. World Neurosurgery. 2023. Vol. 180. P. 1169-193.e3. doi: 10.1016/j.wneu.2023.09.007.

29. Figaji A. An update on pediatric traumatic brain injury. Childs Nerv Syst. 2023. Vol. 39, No. 11. P. 3071-3081. doi: 10.1007/s00381-023-06173-y. Epub 2023 Oct 6. PMID: 37801113; PMCID: PMC10643295.

30. Takala R.S., Posti J.P., Runtti H., et al. Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase-L1 as Outcome Predictors in Traumatic Brain Injury. World Neurosurg. 2016. Vol. 87. P. 8-20. doi: 10.1016/j.wneu.2015.10.066. Epub 2015 Nov 10. PMID: 26547005.