{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:50:09Z","timestamp":1793397009745,"version":"4.5.0"},"reference-count":90,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injury (TBI) is a major global health concern and a leading cause of mortality and disability. Head computed tomography (CT) remains indispensable for the detection of intracranial hemorrhage; however, its indiscriminate use in mild trauma increases radiation exposure, cumulative oncogenic risk, and healthcare costs. Consequently, there is growing interest in tools capable of improving sensitivity in mild or early-stage TBI. Protein-based biomarkers are promising complements to conventional assessment. Molecules such as glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein B (S100B), and neurofilament light chain (NfL) reflect astroglial activation, neuronal injury, and axonal damage, enabling objective evaluation of neurotrauma. Beyond protein biomarkers, metabolomic and lipidomic approaches capture alterations associated with early metabolic distress, oxidative stress, mitochondrial dysfunction, and membrane disruption following TBI. High-resolution mass spectrometry studies have identified reproducible metabolite and lipid signatures correlating with injury severity and functional outcomes. Longitudinal profiling further reveals dynamic metabolic trajectories that distinguish secondary injury progression from stabilization, supporting predictive modeling and risk stratification. Together, these advances pave the way toward precision medicine in neurotrauma. Nevertheless, variability in assay performance and sampling timing continues to limit widespread clinical adoption. Future research should prioritize methodological standardization, analytical validation, and the integration of multi-omic data with machine learning\u2013based predictive models.<\/jats:p>","DOI":"10.3390\/ijms262412158","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:15:21Z","timestamp":1766049321000},"page":"12158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Blood-Based Biomarkers for Traumatic Brain Injury: A New Era in Diagnosis and Prognosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3394-3913","authenticated-orcid":false,"given":"Giulia","family":"Pignataro","sequence":"first","affiliation":[{"name":"Department of Emergency, Anesthesiological and Reanimation Sciences, Fondazione Policlinico Universitario A. Gemelli\u2013IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Sacco Fernandez","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8443-7880","authenticated-orcid":false,"given":"Marcello","family":"Candelli","sequence":"additional","affiliation":[{"name":"Department of Emergency, Anesthesiological and Reanimation Sciences, Fondazione Policlinico Universitario A. Gemelli\u2013IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8616-6929","authenticated-orcid":false,"given":"Gloria","family":"Rozzi","sequence":"additional","affiliation":[{"name":"Department of Emergency, Anesthesiological and Reanimation Sciences, Fondazione Policlinico Universitario A. Gemelli\u2013IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5703-8737","authenticated-orcid":false,"given":"Andrea","family":"Piccioni","sequence":"additional","affiliation":[{"name":"Department of Emergency, Anesthesiological and Reanimation Sciences, Fondazione Policlinico Universitario A. Gemelli\u2013IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelina","family":"Forte","sequence":"additional","affiliation":[{"name":"Department of Emergency, Anesthesiological and Reanimation Sciences, Fondazione Policlinico Universitario A. Gemelli\u2013IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Franceschi","sequence":"additional","affiliation":[{"name":"Department of Emergency, Anesthesiological and Reanimation Sciences, Fondazione Policlinico Universitario A. Gemelli\u2013IRCCS, 00168 Rome, Italy"},{"name":"Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S1474-4422(17)30371-X","article-title":"Traumatic brain injury: Integrated approaches to improve prevention, clinical care, and research","volume":"16","author":"Maas","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.cjtee.2024.03.007","article-title":"Causes and global, regional, and national burdens of traumatic brain injury from 1990 to 2019","volume":"27","author":"Huang","year":"2024","journal-title":"Chin. J. Traumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.mcna.2019.11.001","article-title":"Traumatic Brain Injury: An Overview of Epidemiology, Pathophysiology, and Medical Management","volume":"104","author":"Capizzi","year":"2020","journal-title":"Med. Clin. N. Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"fcac316","DOI":"10.1093\/braincomms\/fcac316","article-title":"Effects of age and time since injury on traumatic brain injury blood biomarkers: A TRACK-TBI study","volume":"5","author":"Gardner","year":"2022","journal-title":"Brain Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S1474-4422(21)00094-6","article-title":"Post-traumatic headache attributed to traumatic brain injury: Classification, clinical characteristics, and treatment","volume":"20","author":"Ashina","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s10194-021-01291-x","article-title":"Mild traumatic brain injury affects the features of migraine","volume":"22","author":"Ishii","year":"2021","journal-title":"J. Headache Pain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1111\/cxo.12670","article-title":"Visual problems associated with traumatic brain injury","volume":"101","author":"Armstrong","year":"2018","journal-title":"Clin. Exp. Optom."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1007\/s00701-023-05743-y","article-title":"Intracranial lesion features in moderate-to-severe traumatic brain injury: Relation to neurointensive care variables and clinical outcome","volume":"165","author":"Enblad","year":"2023","journal-title":"Acta Neurochir."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1089\/neu.2023.0435","article-title":"The Injury Progression in Acute Blast-Induced Mild Traumatic Brain Injury in Rats Reflected by Diffusion Tensor Imaging and Immunohistochemical Examination","volume":"41","author":"Liao","year":"2024","journal-title":"J. Neurotrauma"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/S1474-4422(25)00154-1","article-title":"A new characterisation of acute traumatic brain injury: The NIH-NINDS TBI Classification and Nomenclature Initiative","volume":"24","author":"Manley","year":"2025","journal-title":"Lancet Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1007\/s12028-023-01902-2","article-title":"Guidelines for Neuroprognostication in Critically Ill Adults with Moderate\u2013Severe Traumatic Brain Injury","volume":"40","author":"Muehlschlegel","year":"2024","journal-title":"Neurocrit. Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"106001","DOI":"10.1016\/j.ebiom.2025.106001","article-title":"Beyond mild, moderate, and severe traumatic brain injury: Modelling severity from clinical, neuroimaging, and blood-based indicators","volume":"121","author":"Nelson","year":"2025","journal-title":"EBioMedicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1136\/emermed-2023-213111","article-title":"Fluid biomarkers and neuroimaging in mild traumatic brain injury: Current uses and potential future directions for clinical use in emergency medicine","volume":"40","author":"Newcombe","year":"2023","journal-title":"Emerg. Med. J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ng, S.Y., and Lee, A.Y.W. (2019). Traumatic Brain Injuries: Pathophysiology and Potential Therapeutic Targets. Front Cell Neurosci., 13.","DOI":"10.3389\/fncel.2019.00528"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"149271","DOI":"10.1016\/j.brainres.2024.149271","article-title":"Traumatic brain injury: Symptoms to systems in the 21st century","volume":"1845","author":"Dobson","year":"2024","journal-title":"Brain Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"370312","DOI":"10.1155\/2015\/370312","article-title":"Traumatic brain injury and NADPH oxidase: A deep relationship","volume":"2015","author":"Angeloni","year":"2015","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41582-022-00727-5","article-title":"Astrocytes in the initiation and progression of epilepsy","volume":"18","author":"Vezzani","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108796","DOI":"10.1016\/j.neuropharm.2021.108796","article-title":"Low molecular weight chondroitin sulfate ameliorates pathological changes in 5XFAD mice by improving various functions in the brain","volume":"199","author":"Zhao","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bbi.2021.05.015","article-title":"Functional MHCI deficiency induces ADHD-like symptoms with increased dopamine D1 receptor expression","volume":"97","author":"Meng","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.biopsych.2021.05.025","article-title":"Traumatic Brain Injury and Risk of Neurodegenerative Disorder","volume":"91","author":"Brett","year":"2022","journal-title":"Biol. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e073726","DOI":"10.1136\/bmjopen-2023-073726","article-title":"HEalth and Dementia outcomes following Traumatic Brain Injury (HEAD-TBI): Protocol for a retrospective cohort study","volume":"13","author":"Russell","year":"2023","journal-title":"BMJ Open"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Garza, N., Toussi, A., Wilson, M., Shahlaie, K., and Martin, R. (2020). The Increasing Age of TBI Patients at a Single Level 1 Trauma Center and the Discordance Between GCS and CT Rotterdam Scores in the Elderly. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00112"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1136\/emermed-2022-212549","article-title":"Diagnostic performance of S100B as a rule-out test for intracranial pathology in head-injured patients presenting to the emergency department who meet NICE Head Injury Guideline criteria for CT-head scan","volume":"40","author":"Rogan","year":"2023","journal-title":"Emerg. Med. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1136\/emermed-2020-209471","article-title":"Potential of heart fatty-acid binding protein, neurofilament light, interleukin-10 and S100 calcium-binding protein B in the acute diagnostics and severity assessment of traumatic brain injury","volume":"39","author":"Koivikko","year":"2022","journal-title":"Emerg. Med. J."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Khan, N.A., Asim, M., El-Menyar, A., Biswas, K.H., Rizoli, S., and Al-Thani, H. (2022). The evolving role of extracellular vesicles (exosomes) as biomarkers in traumatic brain injury: Clinical perspectives and therapeutic implications. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.933434"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.1007\/s12035-022-02822-6","article-title":"A Literature Review of Traumatic Brain Injury Biomarkers","volume":"59","author":"Ghaith","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"102735","DOI":"10.1016\/j.bas.2023.102735","article-title":"Blood biomarkers for traumatic brain injury: A narrative review of current evidence","volume":"4","author":"Hossain","year":"2024","journal-title":"Brain Spine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1080\/14737159.2018.1428089","article-title":"An update on diagnostic and prognostic biomarkers for traumatic brain injury","volume":"18","author":"Wang","year":"2018","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1093\/clinchem\/hvae049","article-title":"Blood Biomarkers for the Management of Mild Traumatic Brain Injury in Clinical Practice","volume":"70","author":"Oris","year":"2024","journal-title":"Clin. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1007\/s10072-019-04238-y","article-title":"Biomarkers in traumatic brain injury: New concepts","volume":"41","author":"Slavoaca","year":"2020","journal-title":"Neurol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1139\/bcb-2016-0160","article-title":"Traumatic brain injury: Classification, models, and markers","volume":"96","author":"Najem","year":"2018","journal-title":"Biochem. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e948353","DOI":"10.12659\/MSM.948353","article-title":"GFAP\/UCH-L1 as a Biomarker for Rapid Assessment of Mild TBI in Emergency Departments","volume":"31","author":"Jalali","year":"2025","journal-title":"Med. Sci. Monit."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/s41582-021-00616-3","article-title":"Blood GFAP as an emerging biomarker in brain and spinal cord disorders","volume":"18","author":"Abdelhak","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1042\/BCJ20160082","article-title":"Ubiquitin C-Terminal hydrolase L1 (UCH-L1): Structure, distribution and roles in brain function and dysfunction","volume":"473","author":"Bishop","year":"2016","journal-title":"Biochem. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"14139","DOI":"10.1038\/s41598-024-64125-1","article-title":"Admission levels of serum biomarkers have additive and cumulative prognostic value in traumatic brain injury","volume":"14","author":"Kaaber","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bilgin, Y., Sari, F.M., Gunay, M., Hayme, S., Kantar, Y., and Durmus, U. (2025). Diagnostic accuracy of GFAP and UCH-L1 for intracranial hemorrhage in blunt head trauma: A prospective study. BMC Emerg. Med., 25.","DOI":"10.1186\/s12873-025-01398-3"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1089\/neu.2016.4499","article-title":"Methylprednisolone for the Treatment of Patients with Acute Spinal Cord Injuries: Response","volume":"33","author":"Evaniew","year":"2016","journal-title":"J. Neurotrauma"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/S1474-4422(18)30231-X","article-title":"Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): A multicentre observational study","volume":"17","author":"Bazarian","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Oris, C., Kahouadji, S., Durif, J., Bouvier, D., and Sapin, V. (2023). S100B, Actor and Biomarker of Mild Traumatic Brain Injury. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076602"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"106","DOI":"10.22514\/sv.2024.131","article-title":"Diagnostic role of serum testican and ubiquitin levels in patients with head trauma","volume":"20","author":"Kalafat","year":"2024","journal-title":"Signa Vitae"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S1474-4422(22)00256-3","article-title":"Prognostic value of day-of-injury plasma GFAP and UCH-L1 concentrations for predicting functional recovery after traumatic brain injury in patients from the US TRACK-TBI cohort: An observational cohort study","volume":"21","author":"Korley","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s40364-021-00325-5","article-title":"Blood biomarkers for mild traumatic brain injury: A selective review of unresolved issues","volume":"9","author":"Hier","year":"2021","journal-title":"Biomark. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e534","DOI":"10.1016\/j.wneu.2018.06.234","article-title":"Prognostic Value of Serum Levels of S100 Calcium-Binding Protein B, Neuron-Specific Enolase, and Interleukin-6 in Pediatric Patients with Traumatic Brain Injury","volume":"118","author":"Park","year":"2018","journal-title":"World Neurosurg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"75","DOI":"10.22514\/sv.2025.099","article-title":"A study of the relationship between serum SIRT6 levels and neurological impairment and prognosis after early traumatic brain injury","volume":"21","author":"Deping","year":"2025","journal-title":"Signa Vitae"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Edwards, K.A., Lange, R.T., Lippa, S.M., Brickell, T.A., Gill, J.M., and French, L.M. (2023). Serum GFAP, NfL, and tau concentrations are associated with worse neurobehavioral functioning following mild, moderate, and severe TBI: A cross-sectional multiple-cohort study. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1223960"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.4103\/NRR.NRR-D-24-00286","article-title":"Blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis","volume":"20","author":"Lv","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/ACO.0000000000001468","article-title":"Update on traumatic brain injury in the ICU","volume":"38","author":"Slot","year":"2025","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"105193","DOI":"10.1016\/j.neuint.2021.105193","article-title":"Upregulation of the mGlu5 receptor and COX-2 protein in the mouse brain after imipramine and NS398, searching for mechanisms of regulation","volume":"150","author":"Stachowicz","year":"2021","journal-title":"Neurochem. Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1001\/jamaneurol.2016.0039","article-title":"Time Course and Diagnostic Accuracy of Glial and Neuronal Blood Biomarkers GFAP and UCH-L1 in a Large Cohort of Trauma Patients with and Without Mild Traumatic Brain Injury","volume":"73","author":"Papa","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s11011-016-9801-6","article-title":"Neuron specific enolase: A promising therapeutic target in acute spinal cord injury","volume":"31","author":"Haque","year":"2016","journal-title":"Metab. Brain Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1089\/neu.2023.0419","article-title":"Longitudinal Associations Between Persistent Post-Concussion Symptoms and Blood Biomarkers of Inflammation and CNS-Injury After Mild Traumatic Brain Injury","volume":"41","author":"Clarke","year":"2024","journal-title":"J. Neurotrauma"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1089\/neu.2017.5372","article-title":"Apolipoprotein e \u03f54 Genotype Is Associated with Elevated Psychiatric Distress in Veterans with a History of Mild to Moderate Traumatic Brain Injury","volume":"35","author":"Merritt","year":"2018","journal-title":"J. Neurotrauma"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.jemermed.2019.06.026","article-title":"Analgesic Effect of Nitrous Oxide\/Oxygen Mixture for Traumatic Pain in the Emergency Department: A Randomized, Double-Blind Study","volume":"57","author":"Gao","year":"2019","journal-title":"J. Emerg. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.bbrc.2020.06.056","article-title":"Ligand specificity and affinity in the sulforhodamine B binding RNA aptamer","volume":"529","author":"Piccolo","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.4103\/1673-5374.219025","article-title":"MicroRNAs as diagnostic markers and therapeutic targets for traumatic brain injury","volume":"12","author":"Martinez","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"128","DOI":"10.7150\/ijms.48214","article-title":"MicroRNAs as potential biomarkers for the diagnosis of Traumatic Brain Injury: A systematic review and meta-analysis","volume":"18","author":"Zhou","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1093\/brain\/awab254","article-title":"Evidence and implications of abnormal predictive coding in dementia","volume":"144","author":"Kocagoncu","year":"2021","journal-title":"Brain"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1097\/MAJ.0000000000000506","article-title":"Traumatic brain injury and mitochondrial dysfunction","volume":"350","author":"Hiebert","year":"2015","journal-title":"Am. J. Med. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16225","DOI":"10.1038\/s41598-020-73190-1","article-title":"Identification of a novel CHN1 p.(Phe213Val) variant in a large Han Chinese family with congenital Duane retraction syndrome","volume":"10","author":"Zhou","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1038\/s41467-022-30227-5","article-title":"Serum metabolome associated with severity of acute traumatic brain injury","volume":"13","author":"Thomas","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1021\/acs.jproteome.8b00068","article-title":"Discovery of Lipidome Alterations Following Traumatic Brain Injury via High-Resolution Metabolomics","volume":"17","author":"Hogan","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1186\/s13054-023-04573-9","article-title":"Using metabolomics to predict severe traumatic brain injury outcome (GOSE) at 3 and 12 months","volume":"27","author":"Banoei","year":"2023","journal-title":"Crit. Care"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s11940-022-00742-3","article-title":"Mass Spectrometry-Based Approaches for Clinical Biomarker Discovery in Traumatic Brain Injury","volume":"24","author":"Creech","year":"2022","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Fedoruk, R.P., Lee, C.H., Banoei, M.M., and Winston, B.W. (2023). Metabolomics in severe traumatic brain injury: A scoping review. BMC Neurosci., 24.","DOI":"10.1186\/s12868-023-00824-1"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13054-025-05258-1","article-title":"Metabolomic in severe traumatic brain injury: Exploring primary, secondary injuries, diagnosis, and severity","volume":"29","author":"Banoei","year":"2025","journal-title":"Crit. Care"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"117073","DOI":"10.1016\/j.neuroimage.2020.117073","article-title":"The effect of semantic memory degeneration on creative thinking: A voxel-based morphometry analysis","volume":"220","author":"Paulin","year":"2020","journal-title":"Neuroimage"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1002\/ana.26047","article-title":"Prediction Model of Amyotrophic Lateral Sclerosis by Deep Learning with Patient Induced Pluripotent Stem Cells","volume":"89","author":"Imamura","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"102830","DOI":"10.1016\/j.media.2023.102830","article-title":"Semantic similarity metrics for image registration","volume":"87","author":"Czolbe","year":"2023","journal-title":"Med. Image Anal."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1007\/s10072-022-06558-y","article-title":"The role of spectrin breakdown products in patients with traumatic brain injury: A systematic review and meta-analysis","volume":"44","author":"Liu","year":"2023","journal-title":"Neurol. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/3-211-30714-1_29","article-title":"Matrix metalloproteinase-9 is associated with blood-brain barrier opening and brain edema formation after cortical contusion in rats","volume":"96","author":"Shigemori","year":"2006","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"105642","DOI":"10.1016\/j.neuint.2023.105642","article-title":"Matrix Metalloproteinase-9 inhibitors as therapeutic drugs for traumatic brain injury","volume":"172","author":"Sunny","year":"2024","journal-title":"Neurochem. Int."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"ENEURO.0242-21.2021","DOI":"10.1523\/ENEURO.0242-21.2021","article-title":"Intercellular Adhesion Molecule-1-Induced Posttraumatic Brain Injury Neuropathology in the Prefrontal Cortex and Hippocampus Leads to Sensorimotor Function Deficits and Psychological Stress","volume":"8","author":"Bhowmick","year":"2021","journal-title":"eNeuro"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e1742232024","DOI":"10.1523\/JNEUROSCI.1742-23.2024","article-title":"ICAM-1 Deletion Using CRISPR\/Cas9 Protects the Brain from Traumatic Brain Injury-Induced Inflammatory Leukocyte Adhesion and Transmigration Cascades by Attenuating the Paxillin\/FAK-Dependent Rho GTPase Pathway","volume":"44","author":"Saikia","year":"2024","journal-title":"J. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.1038\/s41598-017-03309-4","article-title":"Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury","volume":"7","author":"Lutton","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"DeDominicis, K.E., Hwang, H., Cartagena, C.M., Shear, D.A., and Boutt\u00e9, A.M. (2018). Cerebrospinal Fluid Biomarkers Are Associated with Glial Fibrillary Acidic Protein and \u03b1II-spectrin Breakdown Products in Brain Tissues Following Penetrating Ballistic-Like Brain Injury in Rats. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00490"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3390\/neurosci4030015","article-title":"Serum Biomarker Concentrations upon Admission in Acute Traumatic Brain Injury: Associations with TBI Severity, Toxoplasma gondii Infection, and Outcome in a Referral Hospital Setting in Cameroon","volume":"4","author":"Buh","year":"2023","journal-title":"NeuroSci"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.3171\/2017.10.JNS17352","article-title":"Estimating the global incidence of traumatic brain injury","volume":"130","author":"Dewan","year":"2019","journal-title":"J. Neurosurg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1093\/brain\/awae350","article-title":"Exploiting blood-based biomarkers to align preclinical models with human traumatic brain injury","volume":"148","author":"Lisi","year":"2025","journal-title":"Brain"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e623","DOI":"10.1212\/WNL.0000000000009985","article-title":"Time course and diagnostic utility of NfL, tau, GFAP, and UCH-L1 in subacute and chronic TBI","volume":"95","author":"Shahim","year":"2020","journal-title":"Neurology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1089\/neur.2021.0017","article-title":"Blood-Brain Barrier Breakdown and Astrocyte Reactivity Evident in the Absence of Behavioral Changes after Repeated Traumatic Brain Injury","volume":"2","author":"Dunn","year":"2021","journal-title":"Neurotrauma Rep."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Boutt\u00e9, A.M., Thangavelu, B., LaValle, C.R., Nemes, J., Gilsdorf, J., Shear, D.A., and Kamimori, G.H. (2019). Brain-related proteins as serum biomarkers of acute, subconcussive blast overpressure exposure: A cohort study of military personnel. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221036"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nrneurol.2016.127","article-title":"Fluid biomarkers for mild traumatic brain injury and related conditions","volume":"12","author":"Zetterberg","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s00701-016-3046-3","article-title":"A review of the clinical utility of serum S100B protein levels in the assessment of traumatic brain injury","volume":"159","author":"Thelin","year":"2017","journal-title":"Acta Neurochir."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S1474-4422(18)30275-8","article-title":"ALERT-TBI study on biomarkers for TBI: Has science suffered?","volume":"17","author":"Maas","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1089\/neu.2019.6762","article-title":"Biomarkers for Traumatic Brain Injury: Data Standards and Statistical Considerations","volume":"38","author":"Huie","year":"2021","journal-title":"J. Neurotrauma"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1089\/neu.2018.6020","article-title":"Cost-Effectiveness of Biomarker Screening for Traumatic Brain Injury","volume":"36","author":"Su","year":"2019","journal-title":"J. Neurotrauma"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1007\/s10143-021-01678-z","article-title":"S100B, GFAP, UCH-L1 and NSE as predictors of abnormalities on CT imaging following mild traumatic brain injury: A systematic review and meta-analysis of diagnostic test accuracy","volume":"45","author":"Amoo","year":"2022","journal-title":"Neurosurg. Rev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S1474-4422(17)30279-X","article-title":"The chronic and evolving neurological consequences of traumatic brain injury","volume":"16","author":"Wilson","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.neuropharm.2018.08.028","article-title":"Circulating microRNAs as biomarkers in traumatic brain injury","volume":"145","author":"Toffolo","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/14737159.2024.2306876","article-title":"The game changer: UCH-L1 and GFAP-based blood test as the first marketed in vitro diagnostic test for mild traumatic brain injury","volume":"24","author":"Kobeissy","year":"2024","journal-title":"Expert Rev. Mol. Diagn."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:20:05Z","timestamp":1766049605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":90,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262412158"],"URL":"https:\/\/doi.org\/10.3390\/ijms262412158","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]}}}