{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:28:14Z","timestamp":1790393294912,"version":"4.1.0"},"reference-count":76,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"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 the leading cause of traumatic death worldwide and is a public health problem associated with high mortality and morbidity rates, with a significant socioeconomic burden. The diagnosis of brain injury may be difficult in some cases or may leave diagnostic doubts, especially in mild trauma with insignificant pathological brain changes or in cases where instrumental tests are negative. Therefore, in recent years, an important area of research has been directed towards the study of new biomarkers, such as micro-RNAs (miRNAs), which can assist clinicians in the diagnosis, staging, and prognostic evaluation of TBI, as well as forensic pathologists in the assessment of TBI and in the estimation of additional relevant data, such as survival time. The aim of this study is to investigate the expression profiles (down- and upregulation) of a panel of miRNAs in subjects deceased with TBI in order to assess, verify, and define the role played by non-coding RNA molecules in the different pathophysiological mechanisms of brain damage. This study also aims to correlate the detected expression profiles with survival time, defined as the time elapsed between the traumatic event and death, and with the severity of the trauma. This study was conducted on 40 cases of subjects deceased with TBI (study group) and 10 cases of subjects deceased suddenly from non-traumatic causes (control group). The study group was stratified according to the survival time and the severity of the trauma. The selection of miRNAs to be examined was based on a thorough literature review. Analyses were performed on formalin-fixed, paraffin-embedded (FFPE) brain tissue samples, with a first step of total RNA extraction and a second step of quantification of the selected miRNAs of interest. This study showed higher expression levels in cases compared to controls for miR-16, miR-21, miR-130a, and miR-155. In contrast, lower expression levels were found in cases compared to controls for miR-23a-3p. There were no statistically significant differences in the expression levels between cases and controls for miR-19a. In cases with short survival, the expression levels of miR-16-5p and miR-21-5p were significantly higher. In cases with long survival, miR-21-5p was significantly lower. The expression levels of miR-130a were significantly higher in TBI cases with short and middle survival. In relation to TBI severity, miR-16-5p and miR-21-5p expression levels were significantly higher in the critical\u2013fatal TBI subgroup. Conclusions: This study provides evidence for the potential of the investigated miRNAs as predictive biomarkers to discriminate between TBI cases and controls. These miRNAs could improve the postmortem diagnosis of TBI and also offer the possibility to define the survival time and the severity of the trauma. The analysis of miRNAs could become a key tool in forensic investigations, providing more precise and detailed information on the nature and extent of TBI and helping to define the circumstances of death.<\/jats:p>","DOI":"10.3390\/ijms25179539","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T12:22:33Z","timestamp":1725366153000},"page":"9539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Analysis of miRNA Expression Profiles in Traumatic Brain Injury (TBI) and Their Correlation with Survival and Severity of Injury"],"prefix":"10.3390","volume":"25","author":[{"given":"Francesca","family":"Consalvo","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cSchola Medica Salernitana\u201d, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2452-7926","authenticated-orcid":false,"given":"Martina","family":"Padovano","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7259-3090","authenticated-orcid":false,"given":"Matteo","family":"Scopetti","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6473-7632","authenticated-orcid":false,"given":"Donato","family":"Morena","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6464-3249","authenticated-orcid":false,"given":"Luigi","family":"Cipolloni","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1686-3236","authenticated-orcid":false,"given":"Vittorio","family":"Fineschi","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5491-3719","authenticated-orcid":false,"given":"Alessandro","family":"Santurro","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cSchola Medica Salernitana\u201d, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"ref_1","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":"2018","journal-title":"J. Neurosurg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1089\/neu.2015.4126","article-title":"Epidemiology of Traumatic Brain Injury in Europe: A Living Systematic Review","volume":"38","author":"Brazinova","year":"2021","journal-title":"J. Neurotrauma"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"535","DOI":"10.23736\/S0390-5616.18.04532-0","article-title":"Epidemiology of severe traumatic brain injury","volume":"62","author":"Iaccarino","year":"2018","journal-title":"J. Neurosurg. Sci."},{"key":"ref_4","unstructured":"GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators (2019). Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol., 18, 56\u201387."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.wneu.2024.01.084","article-title":"Traumatic Brain Injury: A Comprehensive Review of Biomechanics and Molecular Pathophysiology","volume":"185","author":"Orr","year":"2024","journal-title":"World Neurosurg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.2174\/1570159X19666210215123914","article-title":"The Complexity of Secondary Cascade Consequent to Traumatic Brain Injury: Pathobiology and Potential Treatments","volume":"19","author":"Khatri","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Jarrahi, A., Braun, M., Ahluwalia, M., Gupta, R.V., Wilson, M., Munie, S., Ahluwalia, P., Vender, J.R., Vale, F.L., and Dhandapani, K.M. (2020). Revisiting Traumatic Brain Injury: From Molecular Mechanisms to Therapeutic Interventions. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100389"},{"key":"ref_9","first-page":"222","article-title":"Pathophysiology of traumatic brain injury","volume":"18","author":"Mustafa","year":"2013","journal-title":"Neurosciences"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.2174\/1570159X15666170613083606","article-title":"Recent Advances in Pathophysiology of Traumatic Brain Injury","volume":"16","author":"Kaur","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Palmieri, M., Frati, A., Santoro, A., Frati, P., Fineschi, V., and Pesce, A. (2021). Diffuse Axonal Injury: Clinical Prognostic Factors, Molecular Experimental Models and the Impact of the Trauma Related Oxidative Stress. An Extensive Review Concerning Milestones and Advances. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910865"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"He, L., Zhang, R., Yang, M., and Lu, M. (2024). The role of astrocyte in neuroinflammation in traumatic brain injury. Biochim. Biophys. Acta Mol. Basis Dis., 1870.","DOI":"10.1016\/j.bbadis.2023.166992"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"538","DOI":"10.2174\/1570159X17666191101123145","article-title":"Traumatic Brain Injury: A Forensic Approach: A Literature Review","volume":"18","author":"Bertozzi","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Frati, A., Cerretani, D., Fiaschi, A.I., Frati, P., Gatto, V., La Russa, R., Pesce, A., Pinchi, E., Santurro, A., and Fraschetti, F. (2017). Diffuse Axonal Injury and Oxidative Stress: A Comprehensive Review. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122600"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1177\/002580248502500407","article-title":"Microscopic diffuse axonal injury in cases of head injury","volume":"25","author":"Adams","year":"1985","journal-title":"Med. Sci. Law"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1007\/s00414-022-02785-2","article-title":"Forensic biomarkers of lethal traumatic brain injury","volume":"136","author":"Zwirner","year":"2022","journal-title":"Int. J. Leg. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Czy\u017cewski, W., Mazurek, M., Sakwa, L., Szymoniuk, M., Pham, J., Pasierb, B., Litak, J., Czy\u017cewska, E., Turek, M., and Piotrowski, B. (2024). Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury. Cells, 13.","DOI":"10.3390\/cells13020148"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kattan, D., Barsa, C., Mekhijian, S., Shakkour, Z., Jammoul, M., Doumit, M., Zabala, M.C.P., Darwiche, N., Eid, A.H., and Mechref, Y. (2023). Inflammasomes as biomarkers and therapeutic targets in traumatic brain injury and related-neurodegenerative diseases: A comprehensive overview. Neurosci. Biobehav. Rev., 144.","DOI":"10.1016\/j.neubiorev.2022.104969"},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.2147\/JIR.S304461","article-title":"MicroRNA-138-5p Regulates Hippocampal Neuroinflammation and Cognitive Impairment by NLRP3\/Caspase-1 Signaling Pathway in Rats","volume":"14","author":"Feng","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Appel, D., Hummel, R., Weidemeier, M., Endres, K., G\u00f6lz, C., and Sch\u00e4fer, M.K.E. (2021). Pharmacologic Inhibition of ADAM10 Attenuates Brain Tissue Loss, Axonal Injury and Pro-inflammatory Gene Expression Following Traumatic Brain Injury in Mice. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.661462"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1476-4598-13-33","article-title":"Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128","volume":"13","author":"Adlakha","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/mp.2013.93","article-title":"Identification of differentially expressed microRNAs across the developing human brain","volume":"19","author":"Ziats","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1101\/lm.026492.112","article-title":"MicroRNAs in learning, memory, and neurological diseases","volume":"19","author":"Wang","year":"2012","journal-title":"Learn. Mem."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1177\/0271678X18773871","article-title":"MicroRNA-based therapeutics in central nervous system injuries","volume":"38","author":"Sun","year":"2018","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1089\/neu.2022.0296","article-title":"Therapeutic Role of microRNAs of Small Extracellular Vesicles from Human Mesenchymal Stromal\/Stem Cells in Treatment of Experimental Traumatic Brain Injury","volume":"40","author":"Zhang","year":"2023","journal-title":"J. Neurotrauma"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"319","DOI":"10.2174\/1570159X17666191113100808","article-title":"MicroRNAs: The New Challenge for Traumatic Brain Injury Diagnosis","volume":"18","author":"Pinchi","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1080\/21541264.2019.1575159","article-title":"Identify gene expression pattern change at transcriptional and post-transcriptional levels","volume":"10","author":"Zhang","year":"2019","journal-title":"Transcription"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Albano, G.D., Stassi, C., Argo, A., and Zerbo, S. (2023). An Overview on the Use of miRNAs as Possible Forensic Biomarkers for the Diagnosis of Traumatic Brain Injury. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076503"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1089\/neu.2010.1481","article-title":"Human traumatic brain injury alters plasma microRNA levels","volume":"27","author":"Redell","year":"2010","journal-title":"J. Neurotrauma"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bhomia, M., Balakathiresan, N.S., Wang, K.K., Papa, L., and Maheshwari, R.K. (2016). A Panel of Serum MiRNA Biomarkers for the Diagnosis of Severe to Mild Traumatic Brain Injury in Humans. Sci. Rep., 6.","DOI":"10.1038\/srep28148"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1089\/neu.2016.4857","article-title":"MicroRNAs as Novel Biomarkers for the Diagnosis and Prognosis of Mild and Severe Traumatic Brain Injury","volume":"34","author":"Ragusa","year":"2017","journal-title":"J. Neurotrauma"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Qin, X., Li, L., Lv, Q., Shu, Q., Zhang, Y., and Wang, Y. (2018). Expression profile of plasma microRNAs and their roles in diagnosis of mild to severe traumatic brain injury. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0204051"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/jnc.14717","article-title":"Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR-219a-5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1","volume":"150","author":"Yan","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10055","DOI":"10.1523\/JNEUROSCI.1260-14.2014","article-title":"Downregulation of miR-23a and miR-27a following experimental traumatic brain injury induces neuronal cell death through activation of proapoptotic Bcl-2 proteins","volume":"34","author":"Sabirzhanov","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/j.bbrc.2016.12.001","article-title":"Neuroprotective effects of miR-27a against traumatic brain injury via suppressing FoxO3a-mediated neuronal autophagy","volume":"482","author":"Sun","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"59181","DOI":"10.18632\/oncotarget.19469","article-title":"MiR-144 promotes beta-amyloid accumulation-induced cognitive impairments by targeting ADAM10 following traumatic brain injury","volume":"8","author":"Sun","year":"2017","journal-title":"Oncotarget"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.yexcr.2018.03.042","article-title":"MiR-138\/SIRT1 axis is implicated in impaired learning and memory abilities of cerebral ischemia\/reperfusion injured rats","volume":"367","author":"Tian","year":"2018","journal-title":"Exp. Cell Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pinchi, E., Frati, A., Cipolloni, L., Aromatario, M., Gatto, V., La Russa, R., Pesce, A., Santurro, A., Fraschetti, F., and Frati, P. (2018). Clinical-pathological study on \u03b2-APP, IL-1\u03b2, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-20699-1"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bonin, S., D\u2019Errico, S., Medeot, C., Moreschi, C., Ciglieri, S.S., Peruch, M., Concato, M., Azzalini, E., Previder\u00e8, C., and Fattorini, P. (2023). Evaluation of a Set of miRNAs in 26 Cases of Fatal Traumatic Brain Injuries. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310836"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/bja\/aem131","article-title":"Pathophysiology of traumatic brain injury","volume":"99","author":"Werner","year":"2007","journal-title":"Br. J. Anaesth."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Freire, M.A.M., Rocha, G.S., Bittencourt, L.O., Falcao, D., Lima, R.R., and Cavalcanti, J.R.L.P. (2023). Cellular and Molecular Pathophysiology of Traumatic Brain Injury: What Have We Learned So Far?. Biology, 12.","DOI":"10.3390\/biology12081139"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bouras, M., Asehnoune, K., and Roquilly, A. (2022). Immune modulation after traumatic brain injury. Front. Med., 9.","DOI":"10.3389\/fmed.2022.995044"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Defort, P., Retkowska-Tomaszewska, N., Kot, M., Jarmu\u017cek, P., Tylutka, A., and Zembron-Lacny, A. (2022). Inflammatory Predictors of Prognosis in Patients with Traumatic Cerebral Haemorrhage: Retrospective Study. J. Clin. Med., 11.","DOI":"10.3390\/jcm11030705"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/JAD-191150","article-title":"Inflammation in Traumatic Brain Injury","volume":"74","author":"Postolache","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_47","first-page":"97","article-title":"Neuroinflammatory responses to traumatic brain injury: Etiology, clinical consequences, and therapeutic opportunities","volume":"11","author":"Lozano","year":"2015","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Nguyen, A., Nguyen, A., Hsu, T.I., Lew, H.D., Gupta, N., Nguyen, B., Mandavalli, A., Diaz, M.J., and Lucke-Wold, B. (2023). Neutrophil to Lymphocyte Ratio as a Predictor of Postoperative Outcomes in Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Diseases, 11.","DOI":"10.3390\/diseases11010051"},{"key":"ref_49","first-page":"474","article-title":"Neutrophil-to-lymphocyte ratio, past, present and future perspectives","volume":"122","author":"Zahorec","year":"2021","journal-title":"Bratisl. Lek. Listy"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1179069519832286","DOI":"10.1177\/1179069519832286","article-title":"A Review of MicroRNA Biomarkers in Traumatic Brain Injury","volume":"13","author":"Atif","year":"2019","journal-title":"J. Exp. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1038\/s41380-023-02126-8","article-title":"Recent advances in the role of miRNAs in post-traumatic stress disorder and traumatic brain injury","volume":"28","author":"Zhu","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"O\u2019Brien, J., Hayder, H., Zayed, Y., and Peng, C. (2018). Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00402"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"537","DOI":"10.2174\/138920210793175895","article-title":"MicroRNA: Biogenesis, Function and Role in Cancer","volume":"11","author":"Macfarlane","year":"2010","journal-title":"Curr. Genom."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wyczechowska, D., Harch, P.G., Mullenix, S., Fannin, E.S., Chiappinelli, B.B., Jeansonne, D., Lassak, A., Bazan, N.G., and Peruzzi, F. (2023). Serum microRNAs associated with concussion in football players. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1155479"},{"key":"ref_55","first-page":"4746","article-title":"Downregulation of microRNA-16-5p accelerates fracture healing by promoting proliferation and inhibiting apoptosis of osteoblasts in patients with traumatic brain injury","volume":"11","author":"Sun","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ge, X.T., Lei, P., Wang, H.C., Zhang, A.L., Han, Z.L., Chen, X., Li, S.H., Jiang, R.C., Kang, C.S., and Zhang, J.N. (2014). miR-21 improves the neurological outcome after traumatic brain injury in rats. Sci. Rep., 4.","DOI":"10.1038\/srep06718"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.brainres.2015.01.009","article-title":"MiR-21 alleviates secondary blood-brain barrier damage after traumatic brain injury in rats","volume":"1603","author":"Ge","year":"2015","journal-title":"Brain Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1007\/s11064-018-2602-z","article-title":"MicroRNA-21 in the Pathogenesis of Traumatic Brain Injury","volume":"43","author":"Ji","year":"2018","journal-title":"Neurochem. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12974-017-0819-4","article-title":"Microglial-derived microparticles mediate neuroinflammation after traumatic brain injury","volume":"14","author":"Kumar","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.expneurol.2014.12.018","article-title":"Mitochondria-associated microRNAs in rat hippocampus following traumatic brain injury","volume":"265","author":"Wang","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/jcbfm.2011.117","article-title":"Selective CDK inhibitor limits neuroinflammation and progressive neurodegeneration after brain trauma","volume":"32","author":"Kabadi","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/NEN.0000000000000021","article-title":"Progressive neurodegeneration after experimental brain trauma: Association with chronic microglial activation","volume":"73","author":"Loane","year":"2014","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Committee on Medical Aspects of Automotive Safety (1971). Rating the Severity of Tissue Damage: I. The Abbreviated Scale. JAMA, 215, 277\u2013280.","DOI":"10.1001\/jama.215.2.277"},{"key":"ref_64","unstructured":"The Association for the Advancement of Automotive Medicine (2016). Abbreviated Injury Scale (AIS) 2015, The Association for the Advancement of Automotive Medicine."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1111\/nan.12532","article-title":"MiR-16-5p is frequently down-regulated in astrocytic gliomas and modulates glioma cell proliferation, apoptosis and response to cytotoxic therapy","volume":"45","author":"Krell","year":"2019","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"110954","DOI":"10.1016\/j.exger.2020.110954","article-title":"miR-16-5p is upregulated by amyloid \u03b2 deposition in Alzheimer\u2019s disease models and induces neuronal cell apoptosis through direct targeting and suppression of BCL-2","volume":"136","author":"Kim","year":"2020","journal-title":"Exp. Gerontol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Jullienne, A., Fukuda, A.M., Ichkova, A., Nishiyama, N., Aussudre, J., Obenaus, A., and Badaut, J. (2018). Modulating the water channel AQP4 alters miRNA expression, astrocyte connectivity and water diffusion in the rodent brain. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-22268-y"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Vandebroek, A., and Yasui, M. (2020). Regulation of AQP4 in the Central Nervous System. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051603"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.biopha.2018.02.043","article-title":"MiR-21 attenuates apoptosis-triggered by amyloid-\u03b2 via modulating PDCD4\/ PI3K\/AKT\/GSK-3\u03b2 pathway in SH-SY5Y cells","volume":"101","author":"Feng","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10205","DOI":"10.1002\/jcp.27690","article-title":"miR-21 and miR-19b delivered by hMSC-derived EVs regulate the apoptosis and differentiation of neurons in patients with spinal cord injury","volume":"234","author":"Xu","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Bai, X., and Bian, Z. (2022). MicroRNA-21 Is a Versatile Regulator and Potential Treatment Target in Central Nervous System Disorders. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.842288"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1080\/15384101.2019.1691763","article-title":"MicroRNA-23a-3p improves traumatic brain injury through modulating the neurological apoptosis and inflammation response in mice","volume":"19","author":"Li","year":"2020","journal-title":"Cell Cycle"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1096\/fj.201700139RRR","article-title":"MicroRNA-130a regulates cerebral ischemia-induced blood-brain barrier permeability by targeting Homeobox A5","volume":"32","author":"Wang","year":"2018","journal-title":"FASEB J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"12006","DOI":"10.1074\/jbc.M111.280701","article-title":"MicroRNA-130a represses transcriptional activity of aquaporin 4 M1 promoter","volume":"287","author":"Sepramaniam","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s13311-018-0665-9","article-title":"Inhibition of miR-155 Limits Neuroinflammation and Improves Functional Recovery After Experimental Traumatic Brain Injury in Mice","volume":"16","author":"Henry","year":"2019","journal-title":"Neurotherapeutics"},{"key":"ref_76","first-page":"5653","article-title":"Increased miR-155 and heme oxygenase-1 expression is involved in the protective effects of formononetin in traumatic brain injury in rats","volume":"9","author":"Li","year":"2017","journal-title":"Am. J. Transl. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9539\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:47:23Z","timestamp":1760111243000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,2]]},"references-count":76,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25179539"],"URL":"https:\/\/doi.org\/10.3390\/ijms25179539","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,2]]}}}