{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:33:27Z","timestamp":1791848007742,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"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 injuries (TBIs) are a leading cause of mortality and morbidity, particularly in forensic settings where determining the cause of death and timing of injury is critical. Glial fibrillary acidic protein (GFAP), a biomarker specific to astrocytes, has emerged as a valuable tool in post-mortem analyses of TBI. A PRISMA-based literature search included studies examining GFAP in human post-mortem samples such as brain tissue, cerebrospinal fluid (CSF), serum, and urine. The results highlight that GFAP levels correlate with the severity of brain injury, survival interval, and pathological processes such as astrocyte damage and blood\u2013brain barrier disruption. Immunohistochemistry, ELISA, and molecular techniques were commonly employed for GFAP analysis, with notable variability in protocols and thresholds among studies. GFAP demonstrated high diagnostic accuracy in distinguishing TBI-related deaths from other causes, particularly when analyzed in CSF and serum. Furthermore, emerging evidence supports its role in complementing other biomarkers, such as S100B and NFL, to improve diagnostic precision. However, the review also identifies significant methodological heterogeneity and gaps in standardization, which limit the generalizability of findings. Future research should focus on establishing standardized protocols, exploring biomarker combinations, and utilizing advanced molecular tools to enhance the forensic application of GFAP.<\/jats:p>","DOI":"10.3390\/ijms26010185","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T07:34:19Z","timestamp":1735630459000},"page":"185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Role of GFAP in Post-Mortem Analysis of Traumatic Brain Injury: A Systematic Review"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1750-3742","authenticated-orcid":false,"given":"Matteo Antonio","family":"Sacco","sequence":"first","affiliation":[{"name":"Institute of Legal Medicine, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saverio","family":"Gualtieri","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro Pasquale","family":"Tarallo","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Verrina","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Calafiore","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Princi","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Ranno","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Di Cello","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santo","family":"Gratteri","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-6050","authenticated-orcid":false,"given":"Isabella","family":"Aquila","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1080\/16501960410023732","article-title":"Incidence, Risk Factors and Prevention of Mild Traumatic Brain Injury: Results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury","volume":"36","author":"Cassidy","year":"2004","journal-title":"J. Rehabil. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1056\/NEJMcp064645","article-title":"Clinical Practice. Concussion","volume":"356","author":"Ropper","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.apmr.2023.03.036","article-title":"The American Congress of Rehabilitation Medicine Diagnostic Criteria for Mild Traumatic Brain Injury","volume":"104","author":"Silverberg","year":"2023","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3171\/jns.1988.69.3.0381","article-title":"Enhanced Specificity of Prognosis in Severe Head Injury","volume":"69","author":"Choi","year":"1988","journal-title":"J. Neurosurg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1056\/NEJMoa1008069","article-title":"Detection of Blast-Related Traumatic Brain Injury in U.S. Military Personnel","volume":"364","author":"Johnson","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1089\/neu.2013.3040","article-title":"Acute Biomarkers of Traumatic Brain Injury: Relationship Between Plasma Levels of Ubiquitin C-Terminal Hydrolase-L1 and Glial Fibrillary Acidic Protein","volume":"31","author":"Wang","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.1007\/s10143-022-01827-y","article-title":"Interleukin-6 as a prognostic biomarker of clinical outcomes after traumatic brain injury: A systematic review","volume":"45","author":"Ooi","year":"2022","journal-title":"Neurosurg. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3171\/jns.2003.98.1.0205","article-title":"Quantitative Pupillometry, a New Technology: Normative Data and Preliminary Observations in Patients with Acute Head. Injury","volume":"98","author":"Taylor","year":"2003","journal-title":"J. Neurosurg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.annemergmed.2011.07.027","article-title":"S100-B Protein as a Screening Tool for the Early Assessment of Minor Head Injury","volume":"59","author":"Zongo","year":"2012","journal-title":"Ann. Emerg. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cccn.2003.12.008","article-title":"Peripheral Markers of Blood\u2013Brain Barrier Damage","volume":"342","author":"Marchi","year":"2004","journal-title":"Clin. Chim. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"82","DOI":"10.4103\/2152-7806.82248","article-title":"Pupillary Reactivity as an Early Indicator of Increased Intracranial Pressure: The Introduction of the Neurological Pupil Index","volume":"2","author":"Chen","year":"2011","journal-title":"Surg. Neurol. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e622","DOI":"10.1002\/ams2.622","article-title":"Thorough Overview of Ubiquitin C-Terminal Hydrolase-L1 and Glial Fibrillary Acidic Protein as Tandem Biomarkers Cleared by US Food and Drug Administration for the Evaluation of Intracranial Injuries Among Patients with Traumatic Brain Injury","volume":"8","author":"Wang","year":"2021","journal-title":"Acute Med. Surg."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1089\/08977150360517218","article-title":"Time course of cortical hemorrhages after closed traumatic brain injury: Statistical analysis of posttraumatic histomorphological alterations","volume":"20","author":"Oehmichen","year":"2003","journal-title":"J. Neurotrauma"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"146","DOI":"10.4323\/rjlm.2017.146","article-title":"Useful markers to assess traumatic and hypoxic brain injury","volume":"25","author":"Chirica","year":"2017","journal-title":"Rom. J. Leg. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.legalmed.2011.12.007","article-title":"Quantitative analysis of GFAP- and S100 protein-immunopositive astrocytes to investigate the severity of traumatic brain injury","volume":"14","author":"Li","year":"2012","journal-title":"Leg. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s00194-015-0040-7","article-title":"Wundalterdiagnostik nach letalem Sch\u00e4del-Hirn-Trauma","volume":"25","author":"Goede","year":"2015","journal-title":"Rechtsmedizin"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.forsciint.2012.04.025","article-title":"Quantitative immunohistochemical analysis of human brain basic fibroblast growth factor, glial fibrillary acidic protein and single-stranded DNA expressions following traumatic brain injury","volume":"221","author":"Wang","year":"2012","journal-title":"Forensic Sci. Int."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zwirner, J., Bohnert, S., Franke, H., Garland, J., Hammer, N., M\u00f6bius, D., Tse, R., and Ondruschka, B. (2021). Assessing Protein Biomarkers to Detect Lethal Acute Traumatic Brain Injuries in Cerebrospinal Fluid. Biomolecules, 11.","DOI":"10.3390\/biom11111577"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Becerra-Hern\u00e1ndez, L.V., Escobar-Betancourt, M.I., Pimienta-Jim\u00e9nez, H.J., and Buritic\u00e1, E. (2022). Crystallin Alpha-B Overexpression as a Possible Marker of Reactive Astrogliosis in Human Cerebral Contusions. Front. Cell Neurosci., 16.","DOI":"10.3389\/fncel.2022.838551"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.forsciint.2017.09.008","article-title":"Tau protein (MAPT) as a possible biochemical marker of traumatic brain injury in postmortem examination","volume":"280","author":"Olczak","year":"2017","journal-title":"Forensic Sci. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"97","DOI":"10.5114\/fn.2018.76613","article-title":"Brain-originated peptides as possible biochemical markers of traumatic brain injury in cerebrospinal fluid post-mortem examination","volume":"56","author":"Olczak","year":"2018","journal-title":"Folia Neuropathol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kurtulu\u015f Dereli, A., Se\u00e7mem, M., and Acark, K. (2021). Analysis of Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase L1 in Postmortem Serum and Cerebrospinal Fluid in Traumatic Cerebral Deaths. Clin. Exp. Health Sci., 242\u2013248.","DOI":"10.33808\/clinexphealthsci.943779"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Breitling, B., Brunkhorst, R., Verhoff, M., and Foerch, C. (2018). Post-mortem serum concentrations of GFAP correlate with agony time but do not indicate a primary cerebral cause of death. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0205323"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Postupna, N., Rose, S.E., Gibbons, L.E., Coleman, N.M., Hellstern, L.L., Ritchie, K., Wilson, A.M., Cudaback, E., Li, X., and Melief, E.J. (2021). The Delayed Neuropathological Consequences of Traumatic Brain Injury in a Community-Based Sample. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.624696"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1007\/s00414-023-02990-7","article-title":"Post-mortem detection of neuronal and astroglial biochemical markers in serum and urine for diagnostics of traumatic brain injury","volume":"137","author":"Olczak","year":"2023","journal-title":"Int. J. Legal Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.3109\/02699052.2013.837198","article-title":"Beading of the astrocytic processes (clasmatodendrosis) following head trauma is associated with protein degradation pathways","volume":"27","author":"Sakai","year":"2013","journal-title":"Brain Inj."},{"key":"ref_28","first-page":"355","article-title":"Accumulation of Plasma Proteins in Neurons, Purkinje Cells, and Bergmann Glia as a Marker of Functional Disruption of Blood-Brain Barrier in the Early Phase of Traumatic Brain Injury in the Post Mortem Examination","volume":"28","author":"Olczak","year":"2020","journal-title":"J. Leg. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1089\/neu.2014.3575","article-title":"Nestin-Positive Ependymal Cells Are Increased in the Human Spinal Cord after Traumatic Central Nervous System Injury","volume":"32","author":"Cawsey","year":"2015","journal-title":"J. Neurotrauma"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1089\/neu.2017.5441","article-title":"Measurement of Cerebral Biomarkers Proving Traumatic Brain Injuries in Post-Mortem Body Fluids","volume":"35","author":"Ondruschka","year":"2018","journal-title":"J. Neurotrauma"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1089\/neu.2011.2246","article-title":"Cerebellar gene expression following human traumatic brain injury","volume":"29","author":"Staffa","year":"2012","journal-title":"J. Neurotrauma"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1016\/j.legalmed.2009.01.113","article-title":"Routine techniques in forensic neuropathology as demonstrated by gunshot injury to the head","volume":"11","author":"Oehmichen","year":"2009","journal-title":"Leg. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1186\/s13054-015-1081-8","article-title":"Glial fibrillary acidic protein as a biomarker in severe traumatic brain injury patients: A prospective cohort study","volume":"19","author":"Lei","year":"2015","journal-title":"Crit. Care"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tins.2015.04.003","article-title":"Glial fibrillary acidic protein: From intermediate filament assembly and gliosis to neurobiomarker","volume":"38","author":"Yang","year":"2015","journal-title":"Trends Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1212\/WNL.0b013e3181fd62d2","article-title":"GFAP and S100B are biomarkers of traumatic brain injury: An observational cohort study","volume":"75","author":"Vos","year":"2010","journal-title":"Neurology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"134","DOI":"10.15406\/frcij.2023.11.00382","article-title":"GFAP as an immunohistochemical marker in traumatic brain injuries","volume":"11","author":"Khachatryan","year":"2023","journal-title":"Forensic Res. Criminol. Int. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.neulet.2014.01.055","article-title":"Role of GFAP in CNS injuries","volume":"565","author":"Brenner","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1007\/s00414-021-02568-1","article-title":"GFAP positivity in neurons following traumatic brain injuries","volume":"135","author":"Zwirner","year":"2021","journal-title":"Int. J. Legal Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1158\/2159-8290.CD-13-1014","article-title":"Blood-Based Analyses of Cancer: Circulating Tumor Cells and Circulating Tumor DNA","volume":"4","author":"Haber","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Arafah, A., Khatoon, S., Rasool, I., Khan, A., Rather, M.A., Abujabal, K.A., Faqih, Y.A.H., Rashid, H., Rashid, S.M., and Bilal Ahmad, S. (2023). The Future of Precision Medicine in the Cure of Alzheimer\u2019s Disease. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020335"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1093\/brain\/awae035","article-title":"Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles","volume":"147","author":"Pastor","year":"2024","journal-title":"Brain"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1089\/neu.2022.0060","article-title":"Multi-Modal Biomarkers of Repetitive Head Impacts and Traumatic Encephalopathy Syndrome: A Clinicopathological Case Series","volume":"39","author":"Asken","year":"2022","journal-title":"J. Neurotrauma"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Cecchi, R., Camatti, J., Schirripa, M.L., Ragona, M., Pinelli, S., and Cucurachi, N. (Forensic Sci. Med. Pathol., 2024). Postmortem biochemistry of GFAP, NSE and S100B in cerebrospinal fluid and in vitreous humor for estimation of postmortem interval: A pilot study, Forensic Sci. Med. Pathol., ahead of print.","DOI":"10.1007\/s12024-024-00874-9"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1177\/0025817220980601","article-title":"Analysis of the persistence time of the SARS-CoV-2 virus in the cadaver and the risk of passing infection to autopsy staff","volume":"89","author":"Aquila","year":"2021","journal-title":"Med. Leg. J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/185\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:55:35Z","timestamp":1760115335000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,28]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26010185"],"URL":"https:\/\/doi.org\/10.3390\/ijms26010185","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,28]]}}}