{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:07:08Z","timestamp":1782493628946,"version":"3.54.5"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T00:00:00Z","timestamp":1704499200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T00:00:00Z","timestamp":1704499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100011272","name":"FP7 Health","doi-asserted-by":"publisher","award":["602102 (EPITARGET)"],"award-info":[{"award-number":["602102 (EPITARGET)"]}],"id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Polish Ministry of Science and Education","award":["W19\/7.PR\/2014"],"award-info":[{"award-number":["W19\/7.PR\/2014"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epilepsy frequently develops as a result of brain insult; however, there are no tools allowing to predict which patients suffering from trauma will eventually develop epilepsy. microRNAs are interesting candidates for biomarkers, as several of them have been described to change their levels in the brains, and in the plasma of epileptic subjects. This study was conducted to evaluate the usefulness of plasma miRNAs as epileptogenesis\/epilepsy biomarkers. In our studies, we used a rat model of temporal lobe epilepsy. An epileptogenic insult was status epilepticus evoked by stimulation of the left lateral nucleus of the amygdala. Next, animals were continuously video and EEG monitored for 3\u00a0months. Blood was collected at 14, 30, 60, and 90\u00a0days after stimulation. Blood plasma was separated and miRNA levels were analyzed. We compared miRNA levels between sham-operated and stimulated animals, and between animals with high and low numbers of seizures. We propose three miRNAs that could be biomarkers of epilepsy: miR-671, miR-9a-3p and miR-7a-5p. According to us, miR-206-5p is a potential biomarker of epileptogenesis, and miR-221-3p is a potential biomarker of epilepsy severity. We think that these five miRNAs can be considered in the future as potential treatment targets.<\/jats:p>","DOI":"10.1038\/s41598-024-51357-4","type":"journal-article","created":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T12:02:36Z","timestamp":1704542556000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Circulating microRNAs from plasma as preclinical biomarkers of epileptogenesis and epilepsy"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9019-7676","authenticated-orcid":false,"given":"Kinga","family":"Szydlowska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Nizinska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Olszewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1582-0920","authenticated-orcid":false,"given":"Katarzyna","family":"Lukasiuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,6]]},"reference":[{"key":"51357_CR1","unstructured":"Banerjee PN, H. W. Incidence and prevalence. 2nd edn, (Wolters Kluwer Lippincott Williams & Wilkins, UK, 2008)."},{"key":"51357_CR2","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1016\/S0140-6736(14)60456-6","volume":"385","author":"SL Mosh\u00e9","year":"2015","unstructured":"Mosh\u00e9, S. L., Perucca, E., Ryvlin, P. & Tomson, T. Epilepsy: New advances. Lancet 385, 884\u2013898. https:\/\/doi.org\/10.1016\/S0140-6736(14)60456-6 (2015).","journal-title":"Lancet"},{"issue":"Suppl 4","key":"51357_CR3","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/epi.12299","volume":"54","author":"J Engel","year":"2013","unstructured":"Engel, J. et al. Epilepsy biomarkers. Epilepsia 54(Suppl 4), 61\u201369. https:\/\/doi.org\/10.1111\/epi.12299 (2013).","journal-title":"Epilepsia"},{"key":"51357_CR4","doi-asserted-by":"publisher","first-page":"413","DOI":"10.2217\/bmm.13.142","volume":"8","author":"M Hegde","year":"2014","unstructured":"Hegde, M. & Lowenstein, D. H. The search for circulating epilepsy biomarkers. Biomark. Med. 8, 413\u2013427. https:\/\/doi.org\/10.2217\/bmm.13.142 (2014).","journal-title":"Biomark. Med."},{"key":"51357_CR5","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/S1474-4422(16)00112-5","volume":"15","author":"A Pitk\u00e4nen","year":"2016","unstructured":"Pitk\u00e4nen, A. et al. Advances in the development of biomarkers for epilepsy. Lancet Neurol. 15, 843\u2013856. https:\/\/doi.org\/10.1016\/S1474-4422(16)00112-5 (2016).","journal-title":"Lancet Neurol."},{"key":"51357_CR6","doi-asserted-by":"publisher","first-page":"2118","DOI":"10.1172\/JCI92001","volume":"127","author":"LE Walker","year":"2017","unstructured":"Walker, L. E. et al. Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for epilepsy. J. Clin. Invest. 127, 2118\u20132132. https:\/\/doi.org\/10.1172\/JCI92001 (2017).","journal-title":"J. Clin. Invest."},{"key":"51357_CR7","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/s13311-014-0261-6","volume":"11","author":"K Lukasiuk","year":"2014","unstructured":"Lukasiuk, K. & Becker, A. J. Molecular biomarkers of epileptogenesis. Neurotherapeutics 11, 319\u2013323. https:\/\/doi.org\/10.1007\/s13311-014-0261-6 (2014).","journal-title":"Neurotherapeutics"},{"key":"51357_CR8","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1111\/epi.13460","volume":"57","author":"LE Walker","year":"2016","unstructured":"Walker, L. E. et al. WONOEP appraisal: Molecular and cellular biomarkers for epilepsy. Epilepsia 57, 1354\u20131362. https:\/\/doi.org\/10.1111\/epi.13460 (2016).","journal-title":"Epilepsia"},{"key":"51357_CR9","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.phrs.2016.06.031","volume":"111","author":"E Venereau","year":"2016","unstructured":"Venereau, E. et al. HMGB1 as biomarker and drug target. Pharmacol. Res. 111, 534\u2013544. https:\/\/doi.org\/10.1016\/j.phrs.2016.06.031 (2016).","journal-title":"Pharmacol. Res."},{"key":"51357_CR10","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1016\/j.clnu.2018.03.009","volume":"38","author":"M Marchi\u00f2","year":"2019","unstructured":"Marchi\u00f2, M. et al. Decreased ghrelin and des-acyl ghrelin plasma levels in patients affected by pharmacoresistant epilepsy and maintained on the ketogenic diet. Clin. Nutr. 38, 954\u2013957. https:\/\/doi.org\/10.1016\/j.clnu.2018.03.009 (2019).","journal-title":"Clin. Nutr."},{"key":"51357_CR11","doi-asserted-by":"publisher","first-page":"e62","DOI":"10.1212\/WNL.0000000000005741","volume":"91","author":"M Marchi\u00f2","year":"2018","unstructured":"Marchi\u00f2, M. et al. High plasma levels of ghrelin and des-acyl ghrelin in responders to antiepileptic drugs. Neurology 91, e62\u2013e66. https:\/\/doi.org\/10.1212\/WNL.0000000000005741 (2018).","journal-title":"Neurology"},{"key":"51357_CR12","doi-asserted-by":"publisher","first-page":"527","DOI":"10.3390\/jpm12040527","volume":"12","author":"AM Costa","year":"2022","unstructured":"Costa, A. M. et al. Prospective evaluation of ghrelin and des-acyl ghrelin plasma levels in children with newly diagnosed epilepsy: Evidence for reduced ghrelin-to-des-acyl ghrelin ratio in generalized epilepsies. J. Pers. Med. 12, 527. https:\/\/doi.org\/10.3390\/jpm12040527 (2022).","journal-title":"J. Pers. Med."},{"key":"51357_CR13","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3389\/fnmol.2013.00039","volume":"6","author":"P Rao","year":"2013","unstructured":"Rao, P., Benito, E. & Fischer, A. MicroRNAs as biomarkers for CNS disease. Front. Mol. Neurosci. 6, 39. https:\/\/doi.org\/10.3389\/fnmol.2013.00039 (2013).","journal-title":"Front. Mol. Neurosci."},{"key":"51357_CR14","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1261\/rna.2183803","volume":"9","author":"V Ambros","year":"2003","unstructured":"Ambros, V. et al. A uniform system for microRNA annotation. RNA 9, 277\u2013279 (2003).","journal-title":"RNA"},{"key":"51357_CR15","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.cell.2012.04.005","volume":"149","author":"MS Ebert","year":"2012","unstructured":"Ebert, M. S. & Sharp, P. A. Roles for microRNAs in conferring robustness to biological processes. Cell 149, 515\u2013524. https:\/\/doi.org\/10.1016\/j.cell.2012.04.005 (2012).","journal-title":"Cell"},{"key":"51357_CR16","doi-asserted-by":"publisher","first-page":"5127","DOI":"10.1523\/JNEUROSCI.0600-12.2013","volume":"33","author":"A Jovi\u010di\u0107","year":"2013","unstructured":"Jovi\u010di\u0107, A. et al. Comprehensive expression analyses of neural cell-type-specific miRNAs identify new determinants of the specification and maintenance of neuronal phenotypes. J. Neurosci. 33, 5127\u20135137. https:\/\/doi.org\/10.1523\/JNEUROSCI.0600-12.2013 (2013).","journal-title":"J. Neurosci."},{"key":"51357_CR17","doi-asserted-by":"publisher","first-page":"R13","DOI":"10.1186\/gb-2004-5-3-r13","volume":"5","author":"LF Sempere","year":"2004","unstructured":"Sempere, L. F. et al. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol. 5, R13. https:\/\/doi.org\/10.1186\/gb-2004-5-3-r13 (2004).","journal-title":"Genome Biol."},{"key":"51357_CR18","doi-asserted-by":"publisher","first-page":"e35921","DOI":"10.1371\/journal.pone.0035921","volume":"7","author":"RC McKiernan","year":"2012","unstructured":"McKiernan, R. C. et al. Reduced mature microRNA levels in association with dicer loss in human temporal lobe epilepsy with hippocampal sclerosis. PLoS One 7, e35921. https:\/\/doi.org\/10.1371\/journal.pone.0035921 (2012).","journal-title":"PLoS One"},{"key":"51357_CR19","doi-asserted-by":"publisher","first-page":"e76051","DOI":"10.1371\/journal.pone.0076051","volume":"8","author":"AM Bot","year":"2013","unstructured":"Bot, A. M., D\u0119bski, K. J. & Lukasiuk, K. Alterations in miRNA levels in the dentate gyrus in epileptic rats. PLoS One 8, e76051. https:\/\/doi.org\/10.1371\/journal.pone.0076051 (2013).","journal-title":"PLoS One"},{"key":"51357_CR20","doi-asserted-by":"publisher","first-page":"14143","DOI":"10.1038\/srep14143","volume":"5","author":"P Roncon","year":"2015","unstructured":"Roncon, P. et al. MicroRNA profiles in hippocampal granule cells and plasma of rats with pilocarpine-induced epilepsy\u2013comparison with human epileptic samples. Sci. Rep. 5, 14143. https:\/\/doi.org\/10.1038\/srep14143 (2015).","journal-title":"Sci. Rep."},{"key":"51357_CR21","doi-asserted-by":"publisher","first-page":"3328","DOI":"10.1038\/s41598-017-02969-6","volume":"7","author":"R Raoof","year":"2017","unstructured":"Raoof, R. et al. Cerebrospinal fluid microRNAs are potential biomarkers of temporal lobe epilepsy and status epilepticus. Sci. Rep. 7, 3328. https:\/\/doi.org\/10.1038\/s41598-017-02969-6 (2017).","journal-title":"Sci. Rep."},{"key":"51357_CR22","doi-asserted-by":"publisher","first-page":"1782","DOI":"10.1111\/epi.13870","volume":"58","author":"P Bencurova","year":"2017","unstructured":"Bencurova, P. et al. MicroRNA and mesial temporal lobe epilepsy with hippocampal sclerosis: Whole miRNome profiling of human hippocampus. Epilepsia 58, 1782\u20131793. https:\/\/doi.org\/10.1111\/epi.13870 (2017).","journal-title":"Epilepsia"},{"key":"51357_CR23","doi-asserted-by":"publisher","first-page":"702","DOI":"10.3390\/ijms22020702","volume":"22","author":"S De Benedittis","year":"2021","unstructured":"De Benedittis, S. et al. Circulating microRNA: The potential novel diagnostic biomarkers to predict drug resistance in temporal lobe epilepsy, a pilot study. Int. J. Mol. Sci. 22, 702. https:\/\/doi.org\/10.3390\/ijms22020702 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"51357_CR24","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1093\/bioinformatics\/btw008","volume":"32","author":"C Mooney","year":"2016","unstructured":"Mooney, C., Becker, B. A., Raoof, R. & Henshall, D. C. EpimiRBase: A comprehensive database of microRNA-epilepsy associations. Bioinformatics 32, 1436\u20131438. https:\/\/doi.org\/10.1093\/bioinformatics\/btw008 (2016).","journal-title":"Bioinformatics"},{"key":"51357_CR25","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1038\/nm.2834","volume":"18","author":"EM Jimenez-Mateos","year":"2012","unstructured":"Jimenez-Mateos, E. M. et al. Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects. Nat. Med. 18, 1087\u20131094. https:\/\/doi.org\/10.1038\/nm.2834 (2012).","journal-title":"Nat. Med."},{"key":"51357_CR26","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.1016\/j.ajpath.2011.07.036","volume":"179","author":"EM Jimenez-Mateos","year":"2011","unstructured":"Jimenez-Mateos, E. M. et al. miRNA Expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132. Am. J. Pathol. 179, 2519\u20132532. https:\/\/doi.org\/10.1016\/j.ajpath.2011.07.036 (2011).","journal-title":"Am. J. Pathol."},{"key":"51357_CR27","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/jcbfm.2009.186","volume":"30","author":"DZ Liu","year":"2010","unstructured":"Liu, D. Z. et al. Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures. J. Cereb. Blood Flow Metab. 30, 92\u2013101. https:\/\/doi.org\/10.1038\/jcbfm.2009.186 (2010).","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"51357_CR28","doi-asserted-by":"publisher","unstructured":"Wang, J. et al. Circulating microRNAs are promising novel biomarkers for drug-resistant epilepsy. Sci. Rep. 5(1). https:\/\/doi.org\/10.1038\/srep10201 (2015).","DOI":"10.1038\/srep10201"},{"key":"51357_CR29","doi-asserted-by":"publisher","first-page":"9522","DOI":"10.1038\/srep09522","volume":"5","author":"J Wang","year":"2015","unstructured":"Wang, J. et al. Genome-wide circulating microRNA expression profiling indicates biomarkers for epilepsy. Sci. Rep. 5, 9522. https:\/\/doi.org\/10.1038\/srep09522 (2015).","journal-title":"Sci. Rep."},{"key":"51357_CR30","doi-asserted-by":"publisher","first-page":"8665","DOI":"10.1038\/s41598-021-88088-9","volume":"11","author":"K Nizinska","year":"2021","unstructured":"Nizinska, K. et al. Behavioral characteristics as potential biomarkers of the development and phenotype of epilepsy in a rat model of temporal lobe epilepsy. Sci. Rep. 11, 8665. https:\/\/doi.org\/10.1038\/s41598-021-88088-9 (2021).","journal-title":"Sci. Rep."},{"key":"51357_CR31","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","volume":"30","author":"R Edgar","year":"2002","unstructured":"Edgar, R., Domrachev, M. & Lash, A. E. Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30, 207\u2013210. https:\/\/doi.org\/10.1093\/nar\/30.1.207 (2002).","journal-title":"Nucleic Acids Res."},{"key":"51357_CR32","doi-asserted-by":"publisher","first-page":"5245","DOI":"10.1158\/0008-5472.CAN-04-0496","volume":"64","author":"CL Andersen","year":"2004","unstructured":"Andersen, C. L., Jensen, J. L. & \u00d8rntoft, T. F. Normalization of real-time quantitative reverse transcription-PCR data: A model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res. 64, 5245\u20135250. https:\/\/doi.org\/10.1158\/0008-5472.CAN-04-0496 (2004).","journal-title":"Cancer Res."},{"key":"51357_CR33","doi-asserted-by":"publisher","first-page":"R80","DOI":"10.1186\/gb-2004-5-10-r80","volume":"5","author":"RC Gentleman","year":"2004","unstructured":"Gentleman, R. C. et al. Bioconductor: Open software development for computational biology and bioinformatics. Genome Biol. 5, R80. https:\/\/doi.org\/10.1186\/gb-2004-5-10-r80 (2004).","journal-title":"Genome Biol."},{"key":"51357_CR34","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1093\/bioinformatics\/btq431","volume":"26","author":"BS Carvalho","year":"2010","unstructured":"Carvalho, B. S. & Irizarry, R. A. A framework for oligonucleotide microarray preprocessing. Bioinformatics 26, 2363\u20132367. https:\/\/doi.org\/10.1093\/bioinformatics\/btq431 (2010).","journal-title":"Bioinformatics"},{"key":"51357_CR35","unstructured":"R_Core_Team. Vol. http:\/\/www.R-project.org\/ (R Foundation for Statistical Computing, Vienna, 2012)."},{"key":"51357_CR36","unstructured":"Futschik & M. (2012)."},{"key":"51357_CR37","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1016\/S1474-4422(16)30246-0","volume":"15","author":"DC Henshall","year":"2016","unstructured":"Henshall, D. C. et al. MicroRNAs in epilepsy: pathophysiology and clinical utility. Lancet Neurol. 15, 1368\u20131376. https:\/\/doi.org\/10.1016\/S1474-4422(16)30246-0 (2016).","journal-title":"Lancet Neurol."},{"key":"51357_CR38","doi-asserted-by":"publisher","first-page":"9649","DOI":"10.1038\/s41598-021-89084-9","volume":"11","author":"P Bencurova","year":"2021","unstructured":"Bencurova, P. et al. Dynamic miRNA changes during the process of epileptogenesis in an infantile and adult-onset model. Sci. Rep. 11, 9649. https:\/\/doi.org\/10.1038\/s41598-021-89084-9 (2021).","journal-title":"Sci. Rep."},{"key":"51357_CR39","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.bbrc.2016.11.029","volume":"481","author":"R Surges","year":"2016","unstructured":"Surges, R. et al. Changes in serum miRNAs following generalized convulsive seizures in human mesial temporal lobe epilepsy. Biochem. Biophys. Res. Commun. 481, 13\u201318. https:\/\/doi.org\/10.1016\/j.bbrc.2016.11.029 (2016).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"51357_CR40","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1089\/gtmb.2011.0026","volume":"15","author":"A Abou-Zeid","year":"2011","unstructured":"Abou-Zeid, A., Saad, M. & Soliman, E. MicroRNA 146a expression in rheumatoid arthritis: Association with tumor necrosis factor-alpha and disease activity. Genet Test. Mol. Biomarkers 15, 807\u2013812. https:\/\/doi.org\/10.1089\/gtmb.2011.0026 (2011).","journal-title":"Genet Test. Mol. Biomarkers"},{"key":"51357_CR41","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1111\/epi.13915","volume":"58","author":"EA van Vliet","year":"2017","unstructured":"van Vliet, E. A. et al. Standardization procedure for plasma biomarker analysis in rat models of epileptogenesis: Focus on circulating microRNAs. Epilepsia 58, 2013\u20132024. https:\/\/doi.org\/10.1111\/epi.13915 (2017).","journal-title":"Epilepsia"},{"key":"51357_CR42","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.neulet.2010.11.040","volume":"488","author":"K Hu","year":"2011","unstructured":"Hu, K. et al. Expression profile of microRNAs in rat hippocampus following lithium-pilocarpine-induced status epilepticus. Neurosci. Lett. 488, 252\u2013257. https:\/\/doi.org\/10.1016\/j.neulet.2010.11.040 (2011).","journal-title":"Neurosci. Lett."},{"key":"51357_CR43","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.nbd.2013.10.026","volume":"62","author":"JA Gorter","year":"2014","unstructured":"Gorter, J. A. et al. Hippocampal subregion-specific microRNA expression during epileptogenesis in experimental temporal lobe epilepsy. Neurobiol. Dis. 62, 508\u2013520. https:\/\/doi.org\/10.1016\/j.nbd.2013.10.026 (2014).","journal-title":"Neurobiol. Dis."},{"key":"51357_CR44","doi-asserted-by":"publisher","unstructured":"Brennan, G. P. et al. Genome-wide microRNA profiling of plasma from three different animal models identifies biomarkers of temporal lobe epilepsy. Neurobiol. Dis. 144, 105048. https:\/\/doi.org\/10.1016\/j.celrep.2016.02.042 (2020).","DOI":"10.1016\/j.celrep.2016.02.042"},{"key":"51357_CR45","doi-asserted-by":"publisher","first-page":"2402","DOI":"10.1016\/j.celrep.2016.02.042","volume":"14","author":"GP Brennan","year":"2016","unstructured":"Brennan, G. P. et al. Dual and opposing roles of MicroRNA-124 in epilepsy are mediated through inflammatory and NRSF-dependent gene networks. Cell Rep. 14, 2402\u20132412. https:\/\/doi.org\/10.1016\/j.celrep.2016.02.042 (2016).","journal-title":"Cell Rep."},{"key":"51357_CR46","doi-asserted-by":"publisher","first-page":"1948","DOI":"10.1089\/neu.2016.4857","volume":"34","author":"V Di Pietro","year":"2017","unstructured":"Di Pietro, V. et al. MicroRNAs as novel biomarkers for the diagnosis and prognosis of mild and severe traumatic brain injury. J. Neurotrauma 34, 1948\u20131956. https:\/\/doi.org\/10.1089\/neu.2016.4857 (2017).","journal-title":"J. Neurotrauma"},{"key":"51357_CR47","first-page":"88","volume":"1","author":"GM Pasinetti","year":"2012","unstructured":"Pasinetti, G. M., Ho, L., Dooley, C., Abbi, B. & Lange, G. Select non-coding RNA in blood components provide novel clinically accessible biological surrogates for improved identification of traumatic brain injury in OEF\/OIF Veterans. Am. J. Neurodegener Dis. 1, 88\u201398 (2012).","journal-title":"Am. J. Neurodegener Dis."},{"key":"51357_CR48","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/nature11993","volume":"495","author":"TB Hansen","year":"2013","unstructured":"Hansen, T. B. et al. Natural RNA circles function as efficient microRNA sponges. Nature 495, 384\u2013388. https:\/\/doi.org\/10.1038\/nature11993 (2013).","journal-title":"Nature"},{"key":"51357_CR49","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s13195-017-0316-0","volume":"9","author":"KS Sheinerman","year":"2017","unstructured":"Sheinerman, K. S. et al. Circulating brain-enriched microRNAs as novel biomarkers for detection and differentiation of neurodegenerative diseases. Alzheimers Res. Ther. 9, 89. https:\/\/doi.org\/10.1186\/s13195-017-0316-0 (2017).","journal-title":"Alzheimers Res. Ther."},{"key":"51357_CR50","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1002\/2211-5463.12092","volume":"6","author":"EB Harrison","year":"2016","unstructured":"Harrison, E. B. et al. Traumatic brain injury increases levels of miR-21 in extracellular vesicles: Implications for neuroinflammation. FEBS Open Bio 6, 835\u2013846. https:\/\/doi.org\/10.1002\/2211-5463.12092 (2016).","journal-title":"FEBS Open Bio"},{"key":"51357_CR51","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2018.11.005","author":"P Piscopo","year":"2018","unstructured":"Piscopo, P. et al. MicroRNAs and mild cognitive impairment: A systematic review. Ageing Res. Rev. https:\/\/doi.org\/10.1016\/j.arr.2018.11.005 (2018).","journal-title":"Ageing Res. Rev."},{"key":"51357_CR52","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1248\/bpb.b16-00898","volume":"40","author":"CN Wang","year":"2017","unstructured":"Wang, C. N. et al. The anti-dementia effects of donepezil involve miR-206-3p in the hippocampus and cortex. Biol. Pharm. Bull. 40, 465\u2013472. https:\/\/doi.org\/10.1248\/bpb.b16-00898 (2017).","journal-title":"Biol. Pharm. Bull."},{"key":"51357_CR53","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1089\/neu.2017.5111","volume":"35","author":"SD Hicks","year":"2018","unstructured":"Hicks, S. D. et al. Overlapping MicroRNA expression in saliva and cerebrospinal fluid accurately identifies pediatric traumatic brain injury. J. Neurotrauma 35, 64\u201372. https:\/\/doi.org\/10.1089\/neu.2017.5111 (2018).","journal-title":"J. Neurotrauma"},{"key":"51357_CR54","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1007\/s12975-014-0364-8","volume":"5","author":"SS S\u00f8rensen","year":"2014","unstructured":"S\u00f8rensen, S. S., Nygaard, A. B., Nielsen, M. Y., Jensen, K. & Christensen, T. miRNA expression profiles in cerebrospinal fluid and blood of patients with acute ischemic stroke. Transl. Stroke Res. 5, 711\u2013718. https:\/\/doi.org\/10.1007\/s12975-014-0364-8 (2014).","journal-title":"Transl. Stroke Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-51357-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-51357-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-51357-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T12:04:48Z","timestamp":1704542688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-51357-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,6]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["51357"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-51357-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,6]]},"assertion":[{"value":"11 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"708"}}