{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:09:32Z","timestamp":1772168972040,"version":"3.50.1"},"reference-count":13,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP15K20334"],"award-info":[{"award-number":["JP15K20334"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    Traumatic brain injury (TBI) in the form of diffuse axonal injury (DAI) is difficult to diagnose in the early phase of the injury. Early diagnosis of DAI may provide opportunity for developing treatment and management strategies. Tau protein has been demonstrated to increase in the early phase of TBI with high diagnostic accuracy in patients with DAI. We tested the biological plausibility of tau protein using a rat DAI model by evaluating the association between serum tau levels and the severity of brain injury.\u00a0DAI was induced in animals using the Marmarou model.\u00a0After a survival of 60 minutes, rats were anesthetized and sacrificed after obtaining blood samples (5ml) from the heart. Eighteen\u00a0rats\u00a0were\u00a0employed\u00a0in the present study\u00a0and were randomly subjected to sham-operated control (n=4), mild DAI (n=7), and severe DAI (n=7). Of seven severe DAI rats, two rats that had focal injury caused by skull fracture were excluded in the measurement of tau protein level. The serum levels of tau protein in the rat DAI model were found to increase significantly and consistently according to the severity of the injury.\u00a0Rats with DAI showed significantly higher serum levels of tau protein compared to sham rats; the severe DAI rats had higher levels of tau than moderate DAI and sham rats (sham vs. mild,\u00a0\n                    <ns3:italic>P<\/ns3:italic>\n                    =0.02; mild vs. severe,\u00a0\n                    <ns3:italic>P<\/ns3:italic>\n                    =0.02). In conclusion, serum tau protein levels may be useful as a biomarker for diagnosing and estimating the severity of DAI in the early phase.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.21132.1","type":"journal-article","created":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T04:35:07Z","timestamp":1579494907000},"page":"29","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Serum levels of tau protein increase according to the severity of the injury in DAI rat model"],"prefix":"10.12688","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9995-4039","authenticated-orcid":false,"given":"Keisuke","family":"Tomita","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4480-556X","authenticated-orcid":false,"given":"Taka-aki","family":"Nakada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Oshima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeto","family":"Oda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2020,1,20]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"564-74","DOI":"10.1002\/ana.410120611","article-title":"Diffuse axonal injury and traumatic coma in the primate.","volume":"12","author":"T Gennarelli","year":"1982","journal-title":"Ann Neurol."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"838-46","DOI":"10.1097\/TA.0b013e3182127baa","article-title":"Diffuse axonal injury in patients with head injuries: an epidemiologic and prognosis study of 124 cases.","volume":"71","author":"H Chelly","year":"2011","journal-title":"J Trauma."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"95-130","DOI":"10.1016\/s0165-0173(00)00019-9","article-title":"Tau protein isoforms, phosphorylation and role in neurodegenerative disorders.","volume":"33","author":"L Bu\u00e9e","year":"2000","journal-title":"Brain Res Brain Res Rev."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"e0214381","DOI":"10.1371\/journal.pone.0214381","article-title":"Tau protein as a diagnostic marker for diffuse axonal injury.","volume":"14","author":"K Tomita","year":"2019","journal-title":"PLoS One."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"684-92","DOI":"10.1001\/jamaneurol.2014.367","article-title":"Blood biomarkers for brain injury in concussed professional ice hockey players.","volume":"71","author":"P Shahim","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"1063-72","DOI":"10.1001\/jamaneurol.2017.0655","article-title":"Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau-Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers.","volume":"74","author":"R Rubenstein","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"291-300","DOI":"10.3171\/jns.1994.80.2.0291","article-title":"A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics.","volume":"80","author":"A  Marmarou","year":"1994","journal-title":"J Neurosurg."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"239-97","DOI":"10.1016\/B978-012373898-1.50014-0","article-title":"Anesthesia and Analgesia for Laboratory Rodents.","author":"D Gaertner","year":"2008"},{"key":"ref-9","article-title":"Serum levels of tau protein increase according to the severity of the injury in DAI rat model, v2","author":"K Tomita","year":"2020"},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"1654-7","DOI":"10.1097\/TA.0b013e318246887e","article-title":"Neuron-specific enolase and S100BB as outcome predictors in severe diffuse axonal injury.","volume":"72","author":"S Chabok","year":"2012","journal-title":"J Trauma Acute Care Surg."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"1553-61","DOI":"10.1089\/neu.2004.21.1553","article-title":"GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome.","volume":"21","author":"L Pelinka","year":"2004","journal-title":"J Neurotrauma."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"221-6","DOI":"10.3109\/02699052.2010.541895","article-title":"Hyperphosphorylated neurofilament NF-H as a predictor of mortality after brain injury in children.","volume":"25","author":"J Zurek","year":"2011","journal-title":"Brain Inj."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"1205-8","DOI":"10.1016\/j.resuscitation.2010.05.016","article-title":"Relationship between injury severity and serum tau protein levels in traumatic brain injured rats.","volume":"81","author":"P Liliang","year":"2010","journal-title":"Resuscitation."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/9-29\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/9-29\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/9-29\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T04:55:11Z","timestamp":1606712111000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/9-29\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,20]]},"references-count":13,"URL":"https:\/\/doi.org\/10.12688\/f1000research.21132.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.23261.r69132","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.23261.r74640","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.23261.r74639","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.23261.r74639","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.23261.r69132","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.23261.r74640","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,20]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/9-29\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.23261.r69132, Vassilis E Koliatsos, Departments of Pathology, Neurology, and Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA, 17 Aug 2020, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-29\/v1#referee-response-69132","order":0,"name":"referee-response-69132","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.23261.r74640, Mieszko Olczak, Department of Forensic Medicine, Medical University of Warsaw, Warsaw, Poland, 20 Nov 2020, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-29\/v1#referee-response-74640","order":1,"name":"referee-response-74640","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.23261.r74639, Amanda Heslegrave, Department of Neurodegenerative Diseases, University College London, London, UK, 30 Nov 2020, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-29\/v1#referee-response-74639","order":2,"name":"referee-response-74639","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"K.T. was supported by Japan Society for the Promotion of Science [JP15K20334]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}