{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:20:40Z","timestamp":1792059640871,"version":"4.4.0"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K08NS091499"],"award-info":[{"award-number":["K08NS091499"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Traumatic brain injury (TBI) constitutes one of the strongest environmental risk factors for several progressive neurodegenerative disorders of cognitive impairment and dementia that are characterized by the pathological accumulation of hyperphosphorylated tau (p-Tau). It has been questioned whether mouse closed-head TBI models can replicate human TBI-associated tauopathy. We conducted longitudinal histopathological characterization of a mouse closed head TBI model, with a focus on pathological features reported in human TBI-associated tauopathy. Male C57BL\/6\u00a0J mice were subjected to once daily TBI for 5 consecutive days using a weight drop paradigm. Histological analyses (AT8, TDP-43, pTDP-43, NeuN, GFAP, Iba-1, MBP, SMI-312, Prussian blue, IgG, \u03b2APP, alpha-synuclein) were conducted at 1\u00a0week, 4\u00a0weeks, and 24\u00a0weeks after rTBI and compared to sham operated controls. We conducted a systematic review of the literature for mouse models of closed-head injury focusing on studies referencing tau protein assessment. At 1-week post rTBI, p-Tau accumulation was restricted to the corpus callosum and perivascular spaces adjacent to the superior longitudinal fissure. Progressive p-Tau accumulation was observed in the superficial layers of the cerebral cortex, as well as in mammillary bodies and cortical perivascular, subpial, and periventricular locations at 4 to 24\u00a0weeks after rTBI. Associated cortical histopathologies included microvascular injury, neuroaxonal rarefaction, astroglial and microglial activation, and cytoplasmatic localization of TDP-43 and pTDP-43. In our systematic review, less than 1% of mouse studies (25\/3756) reported p-Tau using immunostaining, of which only 3 (0.08%) reported perivascular p-Tau, which is considered a defining feature of chronic traumatic encephalopathy. Commonly reported associated pathologies included neuronal loss (23%), axonal loss (43%), microglial activation and astrogliosis (50%, each), and beta amyloid deposition (29%). Our novel model, supported by systematic review of the literature, indicates progressive tau pathology after closed head murine TBI, highlighting the suitability of mouse models to replicate pertinent human histopathology.<\/jats:p>","DOI":"10.1186\/s40478-021-01220-8","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T20:02:32Z","timestamp":1624996952000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Mouse closed head traumatic brain injury replicates the histological tau pathology pattern of human disease: characterization of a novel model and systematic review of the literature"],"prefix":"10.1186","volume":"9","author":[{"given":"Aydan","family":"Kahriman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Bouley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryl A.","family":"Bosco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L.","family":"Woerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3883-5623","authenticated-orcid":false,"given":"Nils","family":"Henninger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"1220_CR1","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1038\/s41467-017-01068-4","volume":"8","author":"O Albayram","year":"2017","unstructured":"Albayram O, Kondo A, Mannix R, Smith C, Tsai CY, Li C, Herbert MK, Qiu J, Monuteaux M, Driver J et al (2017) Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae. Nat Commun 8:1000. https:\/\/doi.org\/10.1038\/s41467-017-01068-4","journal-title":"Nat Commun"},{"key":"1220_CR2","doi-asserted-by":"publisher","first-page":"8646","DOI":"10.1038\/s41598-019-45234-8","volume":"9","author":"O Albayram","year":"2019","unstructured":"Albayram O, MacIver B, Mathai J, Verstegen A, Baxley S, Qiu C, Bell C, Caldarone BJ, Zhou XZ, Lu KP et al (2019) Traumatic Brain Injury-related voiding dysfunction in mice is caused by damage to rostral pathways, altering inputs to the reflex pathways. Sci Rep 9:8646. https:\/\/doi.org\/10.1038\/s41598-019-45234-8","journal-title":"Sci Rep"},{"key":"1220_CR3","doi-asserted-by":"publisher","first-page":"8949","DOI":"10.1038\/s41598-020-65972-4","volume":"10","author":"M Angoa-Perez","year":"2020","unstructured":"Angoa-Perez M, Zagorac B, Anneken JH, Briggs DI, Winters AD, Greenberg JM, Ahmad M, Theis KR, Kuhn DM (2020) Repetitive, mild traumatic brain injury results in a progressive white matter pathology, cognitive deterioration, and a transient gut microbiota dysbiosis. Sci Rep 10:8949. https:\/\/doi.org\/10.1038\/s41598-020-65972-4","journal-title":"Sci Rep"},{"key":"1220_CR4","doi-asserted-by":"crossref","unstructured":"Anonymous (1999) Consensus conference. Rehabilitation of persons with traumatic brain injury. NIH consensus development panel on rehabilitation of persons with traumatic brain injury. JAMA 282: 974-983","DOI":"10.1001\/jama.282.10.974"},{"key":"1220_CR5","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.1093\/brain\/awaa071","volume":"143","author":"JD Arena","year":"2020","unstructured":"Arena JD, Smith DH, Lee EB, Gibbons GS, Irwin DJ, Robinson JL, Lee VM, Trojanowski JQ, Stewart W, Johnson VE (2020) Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer\u2019s disease. Brain 143:1572\u20131587. https:\/\/doi.org\/10.1093\/brain\/awaa071","journal-title":"Brain"},{"key":"1220_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113180","volume":"326","author":"AD Bachstetter","year":"2020","unstructured":"Bachstetter AD, Morganti JM, Bodnar CN, Webster SJ, Higgins EK, Roberts KN, Snider H, Meier SE, Nation GK, Goulding DS et al (2020) The effects of mild closed head injuries on tauopathy and cognitive deficits in rodents: Primary results in wild type and rTg4510 mice, and a systematic review. Exp Neurol 326:113180. https:\/\/doi.org\/10.1016\/j.expneurol.2020.113180","journal-title":"Exp Neurol"},{"key":"1220_CR7","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1007\/s11682-012-9164-5","volume":"6","author":"CM Baugh","year":"2012","unstructured":"Baugh CM, Stamm JM, Riley DO, Gavett BE, Shenton ME, Lin A, Nowinski CJ, Cantu RC, McKee AC, Stern RA (2012) Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging Behav 6:244\u2013254. https:\/\/doi.org\/10.1007\/s11682-012-9164-5","journal-title":"Brain Imaging Behav"},{"key":"1220_CR8","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1093\/jnen\/nlab001","volume":"80","author":"KF Bieniek","year":"2021","unstructured":"Bieniek KF, Cairns NJ, Crary JF, Dickson DW, Folkerth RD, Keene CD, Litvan I, Perl DP, Stein TD, Vonsattel JP et al (2021) The second NINDS\/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. J Neuropathol Exp Neurol 80:210\u2013219. https:\/\/doi.org\/10.1093\/jnen\/nlab001","journal-title":"J Neuropathol Exp Neurol"},{"key":"1220_CR9","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1089\/neu.2018.6127","volume":"36","author":"CN Bodnar","year":"2019","unstructured":"Bodnar CN, Roberts KN, Higgins EK, Bachstetter AD (2019) A systematic review of closed head injury models of mild traumatic brain injury in mice and rats. J Neurotrauma 36:1683\u20131706. https:\/\/doi.org\/10.1089\/neu.2018.6127","journal-title":"J Neurotrauma"},{"key":"1220_CR10","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1089\/neu.2018.6096","volume":"36","author":"AN Bolton-Hall","year":"2019","unstructured":"Bolton-Hall AN, Hubbard WB, Saatman KE (2019) Experimental designs for repeated mild traumatic brain injury: challenges and considerations. J Neurotrauma 36:1203\u20131221. https:\/\/doi.org\/10.1089\/neu.2018.6096","journal-title":"J Neurotrauma"},{"key":"1220_CR11","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1089\/neu.2018.5844","volume":"36","author":"J Bouley","year":"2019","unstructured":"Bouley J, Chung DY, Ayata C, Brown RH Jr, Henninger N (2019) Cortical spreading depression denotes concussion injury. J Neurotrauma 36:1008\u20131017. https:\/\/doi.org\/10.1089\/neu.2018.5844","journal-title":"J Neurotrauma"},{"key":"1220_CR12","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/s0021-9290(00)00135-4","volume":"34","author":"DR Bradshaw","year":"2001","unstructured":"Bradshaw DR, Ivarsson J, Morfey CL, Viano DC (2001) Simulation of acute subdural hematoma and diffuse axonal injury in coronal head impact. J Biomech 34:85\u201394. https:\/\/doi.org\/10.1016\/s0021-9290(00)00135-4","journal-title":"J Biomech"},{"key":"1220_CR13","doi-asserted-by":"publisher","first-page":"2869","DOI":"10.1016\/j.ajpath.2016.07.013","volume":"186","author":"DI Briggs","year":"2016","unstructured":"Briggs DI, Angoa-Perez M, Kuhn DM (2016) Prolonged repetitive head trauma induces a singular chronic traumatic encephalopathy-like pathology in white matter despite transient behavioral abnormalities. Am J Pathol 186:2869\u20132886. https:\/\/doi.org\/10.1016\/j.ajpath.2016.07.013","journal-title":"Am J Pathol"},{"key":"1220_CR14","doi-asserted-by":"publisher","unstructured":"Cansler SM, Guilhaume-Correa F, Day D, Bedolla A, Evanson NK Indirect traumatic optic neuropathy after head trauma in adolescent male mice is associated with behavioral visual impairment, neurodegeneration, and elevated endoplasmic reticulum stress markers at acute and subacute times. BioRxiv [Preprint] June 12, 2020 (Cited 06\/01\/2021). https:\/\/doi.org\/10.1101\/2020.06.11.144766","DOI":"10.1101\/2020.06.11.144766"},{"key":"1220_CR15","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s13195-018-0461-0","volume":"11","author":"WH Cheng","year":"2019","unstructured":"Cheng WH, Martens KM, Bashir A, Cheung H, Stukas S, Gibbs E, Namjoshi DR, Button EB, Wilkinson A, Barron CJ et al (2019) CHIMERA repetitive mild traumatic brain injury induces chronic behavioural and neuropathological phenotypes in wild-type and APP\/PS1 mice. Alzheimers Res Ther 11:6. https:\/\/doi.org\/10.1186\/s13195-018-0461-0","journal-title":"Alzheimers Res Ther"},{"key":"1220_CR16","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1007\/s10439-008-9510-3","volume":"36","author":"RJ Cloots","year":"2008","unstructured":"Cloots RJ, Gervaise HM, van Dommelen JA, Geers MG (2008) Biomechanics of traumatic brain injury: influences of the morphologic heterogeneities of the cerebral cortex. Ann Biomed Eng 36:1203\u20131215. https:\/\/doi.org\/10.1007\/s10439-008-9510-3","journal-title":"Ann Biomed Eng"},{"key":"1220_CR17","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1001\/jamaneurol.2016.1948","volume":"73","author":"PK Crane","year":"2016","unstructured":"Crane PK, Gibbons LE, Dams-O\u2019Connor K, Trittschuh E, Leverenz JB, Keene CD, Sonnen J, Montine TJ, Bennett DA, Leurgans S et al (2016) Association of traumatic brain injury with late-life neurodegenerative conditions and neuropathologic findings. JAMA Neurol 73:1062\u20131069. https:\/\/doi.org\/10.1001\/jamaneurol.2016.1948","journal-title":"JAMA Neurol"},{"key":"1220_CR18","doi-asserted-by":"publisher","first-page":"2737","DOI":"10.1089\/neu.2018.5778","volume":"35","author":"DS DeWitt","year":"2018","unstructured":"DeWitt DS, Hawkins BE, Dixon CE, Kochanek PM, Armstead W, Bass CR, Bramlett HM, Buki A, Dietrich WD, Ferguson AR et al (2018) Pre-clinical testing of therapies for traumatic brain injury. J Neurotrauma 35:2737\u20132754. https:\/\/doi.org\/10.1089\/neu.2018.5778","journal-title":"J Neurotrauma"},{"key":"1220_CR19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0197346","volume":"13","author":"NK Evanson","year":"2018","unstructured":"Evanson NK, Guilhaume-Correa F, Herman JP, Goodman MD (2018) Optic tract injury after closed head traumatic brain injury in mice: A model of indirect traumatic optic neuropathy. PLoS ONE 13:e0197346. https:\/\/doi.org\/10.1371\/journal.pone.0197346","journal-title":"PLoS ONE"},{"key":"1220_CR20","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1136\/bmj.331.7530.1419","volume":"331","author":"S Fleminger","year":"2005","unstructured":"Fleminger S, Ponsford J (2005) Long term outcome after traumatic brain injury. BMJ 331:1419\u20131420. https:\/\/doi.org\/10.1136\/bmj.331.7530.1419","journal-title":"BMJ"},{"key":"1220_CR21","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1038\/s41467-019-10428-1","volume":"10","author":"J Gamache","year":"2019","unstructured":"Gamache J, Benzow K, Forster C, Kemper L, Hlynialuk C, Furrow E, Ashe KH, Koob MD (2019) Factors other than hTau overexpression that contribute to tauopathy-like phenotype in rTg4510 mice. Nat Commun 10:2479. https:\/\/doi.org\/10.1038\/s41467-019-10428-1","journal-title":"Nat Commun"},{"key":"1220_CR22","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.csm.2010.09.007","volume":"30","author":"BE Gavett","year":"2011","unstructured":"Gavett BE, Stern RA, McKee AC (2011) Chronic traumatic encephalopathy: a potential late effect of sport-related concussive and subconcussive head trauma. Clin Sports Med 30:179\u2013188. https:\/\/doi.org\/10.1016\/j.csm.2010.09.007","journal-title":"Clin Sports Med"},{"key":"1220_CR23","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1093\/brain\/aww317","volume":"140","author":"M Ghajari","year":"2017","unstructured":"Ghajari M, Hellyer PJ, Sharp DJ (2017) Computational modelling of traumatic brain injury predicts the location of chronic traumatic encephalopathy pathology. Brain 140:333\u2013343. https:\/\/doi.org\/10.1093\/brain\/aww317","journal-title":"Brain"},{"key":"1220_CR24","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1146\/annurev-neuro-072116-031153","volume":"40","author":"M Goedert","year":"2017","unstructured":"Goedert M, Eisenberg DS, Crowther RA (2017) Propagation of tau aggregates and neurodegeneration. Annu Rev Neurosci 40:189\u2013210. https:\/\/doi.org\/10.1146\/annurev-neuro-072116-031153","journal-title":"Annu Rev Neurosci"},{"key":"1220_CR25","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13041-017-0298-7","volume":"10","author":"M Goedert","year":"2017","unstructured":"Goedert M, Spillantini MG (2017) Propagation of tau aggregates. Mol. Brain 10:18. https:\/\/doi.org\/10.1186\/s13041-017-0298-7","journal-title":"Brain"},{"key":"1220_CR26","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1126\/scitranslmed.3003716","volume":"4","author":"LE Goldstein","year":"2012","unstructured":"Goldstein LE, Fisher AM, Tagge CA, Zhang XL, Velisek L, Sullivan JA, Upreti C, Kracht JM, Ericsson M, Wojnarowicz MW et al (2012) Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci Transl Med 4:134\u2013160. https:\/\/doi.org\/10.1126\/scitranslmed.3003716","journal-title":"Sci Transl Med"},{"key":"1220_CR27","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1136\/jnnp-2017-317557","volume":"90","author":"NS Graham","year":"2019","unstructured":"Graham NS, Sharp DJ (2019) Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia. J Neurol Neurosurg Psychiatry 90:1221\u20131233. https:\/\/doi.org\/10.1136\/jnnp-2017-317557","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"1220_CR28","doi-asserted-by":"publisher","first-page":"3550","DOI":"10.1093\/brain\/awz290","volume":"142","author":"AD Griffin","year":"2019","unstructured":"Griffin AD, Turtzo LC, Parikh GY, Tolpygo A, Lodato Z, Moses AD, Nair G, Perl DP, Edwards NA, Dardzinski BJ et al (2019) Traumatic microbleeds suggest vascular injury and predict disability in traumatic brain injury. Brain 142:3550\u20133564. https:\/\/doi.org\/10.1093\/brain\/awz290","journal-title":"Brain"},{"key":"1220_CR29","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1212\/wnl.54.6.1316","volume":"54","author":"Z Guo","year":"2000","unstructured":"Guo Z, Cupples LA, Kurz A, Auerbach SH, Volicer L, Chui H, Green RC, Sadovnick AD, Duara R, DeCarli C et al (2000) Head injury and the risk of AD in the MIRAGE study. Neurology 54:1316\u20131323. https:\/\/doi.org\/10.1212\/wnl.54.6.1316","journal-title":"Neurology"},{"key":"1220_CR30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2021461118","author":"MT Gyparaki","year":"2021","unstructured":"Gyparaki MT, Arab A, Sorokina EM, Santiago-Ruiz AN, Bohrer CH, Xiao J, Lakadamyali M (2021) Tau forms oligomeric complexes on microtubules that are distinct from tau aggregates. Proc Natl Acad Sci U S A. https:\/\/doi.org\/10.1073\/pnas.2021461118","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1220_CR31","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1093\/brain\/aww001","volume":"139","author":"N Henninger","year":"2016","unstructured":"Henninger N, Bouley J, Sikoglu EM, An J, Moore CM, King JA, Bowser R, Freeman MR, Brown RH Jr (2016) Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1. Brain 139:1094\u20131105. https:\/\/doi.org\/10.1093\/brain\/aww001","journal-title":"Brain"},{"key":"1220_CR32","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3389\/fnagi.2020.00011","volume":"12","author":"F Hernandez","year":"2020","unstructured":"Hernandez F, Merchan-Rubira J, Valles-Saiz L, Rodriguez-Matellan A, Avila J (2020) Differences between human and murine tau at the N-terminal end. Front Aging Neurosci 12:11. https:\/\/doi.org\/10.3389\/fnagi.2020.00011","journal-title":"Front Aging Neurosci"},{"key":"1220_CR33","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/j.jalz.2016.03.018","volume":"12","author":"DM Holtzman","year":"2016","unstructured":"Holtzman DM, Carrillo MC, Hendrix JA, Bain LJ, Catafau AM, Gault LM, Goedert M, Mandelkow E, Mandelkow EM, Miller DS et al (2016) Tau: From research to clinical development. Alzheimers Dement 12:1033\u20131039. https:\/\/doi.org\/10.1016\/j.jalz.2016.03.018","journal-title":"Alzheimers Dement"},{"key":"1220_CR34","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1007\/s00401-018-1902-3","volume":"136","author":"ET Hsu","year":"2018","unstructured":"Hsu ET, Gangolli M, Su S, Holleran L, Stein TD, Alvarez VE, McKee AC, Schmidt RE, Brody DL (2018) Astrocytic degeneration in chronic traumatic encephalopathy. Acta Neuropathol 136:955\u2013972. https:\/\/doi.org\/10.1007\/s00401-018-1902-3","journal-title":"Acta Neuropathol"},{"key":"1220_CR35","doi-asserted-by":"publisher","first-page":"309","DOI":"10.3233\/JAD-130182","volume":"37","author":"BR Huber","year":"2013","unstructured":"Huber BR, Meabon JS, Martin TJ, Mourad PD, Bennett R, Kraemer BC, Cernak I, Petrie EC, Emery MJ, Swenson ER et al (2013) Blast exposure causes early and persistent aberrant phospho- and cleaved-tau expression in a murine model of mild blast-induced traumatic brain injury. J Alzheimers Dis 37:309\u2013323. https:\/\/doi.org\/10.3233\/JAD-130182","journal-title":"J Alzheimers Dis"},{"key":"1220_CR36","doi-asserted-by":"publisher","first-page":"341","DOI":"10.3233\/NRE-2007-22502","volume":"22","author":"AA Hyder","year":"2007","unstructured":"Hyder AA, Wunderlich CA, Puvanachandra P, Gururaj G, Kobusingye OC (2007) The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation 22:341\u2013353","journal-title":"NeuroRehabilitation"},{"key":"1220_CR37","doi-asserted-by":"publisher","first-page":"16180","DOI":"10.1523\/JNEUROSCI.3020-14.2014","volume":"34","author":"JJ Iliff","year":"2014","unstructured":"Iliff JJ, Chen MJ, Plog BA, Zeppenfeld DM, Soltero M, Yang L, Singh I, Deane R, Nedergaard M (2014) Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. J Neurosci 34:16180\u201316193. https:\/\/doi.org\/10.1523\/JNEUROSCI.3020-14.2014","journal-title":"J Neurosci"},{"key":"1220_CR38","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.neubiorev.2015.05.008","volume":"56","author":"GL Iverson","year":"2015","unstructured":"Iverson GL, Gardner AJ, McCrory P, Zafonte R, Castellani RJ (2015) A critical review of chronic traumatic encephalopathy. Neurosci Biobehav Rev 56:276\u2013293. https:\/\/doi.org\/10.1016\/j.neubiorev.2015.05.008","journal-title":"Neurosci Biobehav Rev"},{"issue":"Pt 3","key":"1220_CR39","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.expneurol.2015.05.019","volume":"275","author":"K Kenney","year":"2016","unstructured":"Kenney K, Amyot F, Haber M, Pronger A, Bogoslovsky T, Moore C, Diaz-Arrastia R (2016) Cerebral vascular injury in traumatic brain injury. Exp Neurol 275(Pt 3):353\u2013366. https:\/\/doi.org\/10.1016\/j.expneurol.2015.05.019","journal-title":"Exp Neurol"},{"key":"1220_CR40","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1038\/nature14658","volume":"523","author":"A Kondo","year":"2015","unstructured":"Kondo A, Shahpasand K, Mannix R, Qiu J, Moncaster J, Chen CH, Yao Y, Lin YM, Driver JA, Sun Y et al (2015) Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy. Nature 523:431\u2013436. https:\/\/doi.org\/10.1038\/nature14658","journal-title":"Nature"},{"key":"1220_CR41","doi-asserted-by":"publisher","first-page":"96","DOI":"10.3389\/fnagi.2020.00096","volume":"12","author":"GG Kovacs","year":"2020","unstructured":"Kovacs GG (2020) Astroglia and Tau: new perspectives. Front Aging Neurosci 12:96. https:\/\/doi.org\/10.3389\/fnagi.2020.00096","journal-title":"Front Aging Neurosci"},{"key":"1220_CR42","doi-asserted-by":"publisher","first-page":"9176","DOI":"10.1111\/jcmm.15555","volume":"24","author":"B Liu","year":"2020","unstructured":"Liu B, Cao Y, Shi F, Wang L, Li N, Cheng X, Du J, Tian Q, Zhou X (2020) The overexpression of RBM3 alleviates TBI-induced behaviour impairment and AD-like tauopathy in mice. J Cell Mol Med 24:9176\u20139188. https:\/\/doi.org\/10.1111\/jcmm.15555","journal-title":"J Cell Mol Med"},{"key":"1220_CR43","doi-asserted-by":"publisher","DOI":"10.5812\/archneurosci.44254","author":"AF Logsdon","year":"2017","unstructured":"Logsdon AF, Lucke-Wold BP, Turner RC, Li X, Adkins CE, Mohammad AS, Huber JD, Rosen CL, Lockman PR (2017) A mouse model of focal vascular injury induces astrocyte reactivity, tau oligomers, and aberrant behavior. Arch Neurosci. https:\/\/doi.org\/10.5812\/archneurosci.44254","journal-title":"Arch Neurosci"},{"key":"1220_CR44","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3389\/fneur.2014.00012","volume":"5","author":"J Luo","year":"2014","unstructured":"Luo J, Nguyen A, Villeda S, Zhang H, Ding Z, Lindsey D, Bieri G, Castellano JM, Beaupre GS, Wyss-Coray T (2014) Long-term cognitive impairments and pathological alterations in a mouse model of repetitive mild traumatic brain injury. Front Neurol 5:12. https:\/\/doi.org\/10.3389\/fneur.2014.00012","journal-title":"Front Neurol"},{"key":"1220_CR45","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/B978-0-444-63954-7.00028-8","volume":"158","author":"AC McKee","year":"2018","unstructured":"McKee AC, Abdolmohammadi B, Stein TD (2018) The neuropathology of chronic traumatic encephalopathy. Handb Clin Neurol 158:297\u2013307. https:\/\/doi.org\/10.1016\/B978-0-444-63954-7.00028-8","journal-title":"Handb Clin Neurol"},{"key":"1220_CR46","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00401-015-1515-z","volume":"131","author":"AC McKee","year":"2016","unstructured":"McKee AC, Cairns NJ, Dickson DW, Folkerth RD, Keene CD, Litvan I, Perl DP, Stein TD, Vonsattel JP, Stewart W et al (2016) The first NINDS\/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta Neuropathol 131:75\u201386. https:\/\/doi.org\/10.1007\/s00401-015-1515-z","journal-title":"Acta Neuropathol"},{"key":"1220_CR47","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1097\/NEN.0b013e3181ee7d85","volume":"69","author":"AC McKee","year":"2010","unstructured":"McKee AC, Gavett BE, Stern RA, Nowinski CJ, Cantu RC, Kowall NW, Perl DP, Hedley-Whyte ET, Price B, Sullivan C et al (2010) TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J Neuropathol Exp Neurol 69:918\u2013929. https:\/\/doi.org\/10.1097\/NEN.0b013e3181ee7d85","journal-title":"J Neuropathol Exp Neurol"},{"key":"1220_CR48","doi-asserted-by":"publisher","first-page":"S242","DOI":"10.1016\/j.jalz.2014.04.003","volume":"10","author":"AC McKee","year":"2014","unstructured":"McKee AC, Robinson ME (2014) Military-related traumatic brain injury and neurodegeneration. Alzheimers Dement 10:S242-253. https:\/\/doi.org\/10.1016\/j.jalz.2014.04.003","journal-title":"Alzheimers Dement"},{"key":"1220_CR49","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1001\/jama.2017.8334","volume":"318","author":"J Mez","year":"2017","unstructured":"Mez J, Daneshvar DH, Kiernan PT, Abdolmohammadi B, Alvarez VE, Huber BR, Alosco ML, Solomon TM, Nowinski CJ, McHale L et al (2017) Clinicopathological evaluation of chronic traumatic encephalopathy in players of american football. JAMA 318:360\u2013370. https:\/\/doi.org\/10.1001\/jama.2017.8334","journal-title":"JAMA"},{"key":"1220_CR50","doi-asserted-by":"publisher","first-page":"1902","DOI":"10.1089\/neu.2019.6436","volume":"37","author":"GM Niziolek","year":"2020","unstructured":"Niziolek GM, Boudreau RM, Baker J, Friend LA, Makley AT, Edwards MJ, Gulbins E, Goodman MD (2020) Acid sphingomyelinase inhibition mitigates histopathological and behavioral changes in a murine model of traumatic brain injury. J Neurotrauma 37:1902\u20131909. https:\/\/doi.org\/10.1089\/neu.2019.6436","journal-title":"J Neurotrauma"},{"key":"1220_CR51","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.jss.2020.09.034","volume":"259","author":"GM Niziolek","year":"2021","unstructured":"Niziolek GM, Hoehn RS, Seitz AP, Jernigan PL, Makley AT, Gulbins E, Edwards MJ, Goodman MD (2021) The role of acid sphingomyelinase inhibition in repetitive mild traumatic brain injury. J Surg Res 259:296\u2013304. https:\/\/doi.org\/10.1016\/j.jss.2020.09.034","journal-title":"J Surg Res"},{"key":"1220_CR52","volume-title":"The mouse brain in stereotaxic coordinates","author":"G Paxinos","year":"2013","unstructured":"Paxinos G, Franklin KBJ (2013) The mouse brain in stereotaxic coordinates. Elsevier Academic Press, Cambridge"},{"key":"1220_CR53","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1007\/s00701-015-2512-7","volume":"157","author":"W Peeters","year":"2015","unstructured":"Peeters W, van den Brande R, Polinder S, Brazinova A, Steyerberg EW, Lingsma HF, Maas AI (2015) Epidemiology of traumatic brain injury in Europe. Acta Neurochir (Wien) 157:1683\u20131696. https:\/\/doi.org\/10.1007\/s00701-015-2512-7","journal-title":"Acta Neurochir (Wien)"},{"key":"1220_CR54","doi-asserted-by":"publisher","first-page":"184","DOI":"10.4103\/2152-7806.147566","volume":"5","author":"AL Petraglia","year":"2014","unstructured":"Petraglia AL, Plog BA, Dayawansa S, Dashnaw ML, Czerniecka K, Walker CT, Chen M, Hyrien O, Iliff JJ, Deane R et al (2014) The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy. Surg Neurol Int 5:184. https:\/\/doi.org\/10.4103\/2152-7806.147566","journal-title":"Surg Neurol Int"},{"key":"1220_CR55","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1093\/jnen\/nlaa130","volume":"80","author":"J Rajic Bumber","year":"2021","unstructured":"Rajic Bumber J, Pilipovic K, Jankovic T, Dolenec P, Grzeta N, Kriz J, Zupan G (2021) Repetitive traumatic brain injury is associated with TDP-43 alterations, neurodegeneration, and glial activation in mice. J Neuropathol Exp Neurol 80:2\u201314. https:\/\/doi.org\/10.1093\/jnen\/nlaa130","journal-title":"J Neuropathol Exp Neurol"},{"key":"1220_CR56","doi-asserted-by":"publisher","first-page":"2854","DOI":"10.1093\/cercor\/bhx164","volume":"28","author":"SU Rehman","year":"2018","unstructured":"Rehman SU, Ahmad A, Yoon GH, Khan M, Abid MN, Kim MO (2018) Inhibition of c-Jun N-terminal kinase protects against brain damage and improves learning and memory after traumatic brain injury in adult mice. Cereb Cortex 28:2854\u20132872. https:\/\/doi.org\/10.1093\/cercor\/bhx164","journal-title":"Cereb Cortex"},{"key":"1220_CR57","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1089\/neu.2015.4288","volume":"33","author":"JJ Sabbagh","year":"2016","unstructured":"Sabbagh JJ, Fontaine SN, Shelton LB, Blair LJ, Hunt JB Jr, Zhang B, Gutmann JM, Lee DC, Lloyd JD, Dickey CA (2016) Noncontact rotational head injury produces transient cognitive deficits but lasting neuropathological changes. J Neurotrauma 33:1751\u20131760. https:\/\/doi.org\/10.1089\/neu.2015.4288","journal-title":"J Neurotrauma"},{"key":"1220_CR58","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1089\/hum.2019.174","volume":"31","author":"CB Sacramento","year":"2020","unstructured":"Sacramento CB, Sondhi D, Rosenberg JB, Chen A, Giordano S, Pey E, Lee V, Stiles KM, Havlicek DF, Leopold PL et al (2020) Anti-phospho-tau gene therapy for chronic traumatic encephalopathy. Hum Gene Ther 31:57\u201369. https:\/\/doi.org\/10.1089\/hum.2019.174","journal-title":"Hum Gene Ther"},{"key":"1220_CR59","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1126\/science.1113694","volume":"309","author":"K Santacruz","year":"2005","unstructured":"Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, DeTure M, Ramsden M, McGowan E et al (2005) Tau suppression in a neurodegenerative mouse model improves memory function. Science 309:476\u2013481. https:\/\/doi.org\/10.1126\/science.1113694","journal-title":"Science"},{"key":"1220_CR60","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9:671\u2013675. https:\/\/doi.org\/10.1038\/nmeth.2089","journal-title":"Nat Methods"},{"key":"1220_CR61","unstructured":"Schneider J, Jeon S, Gladman JT, Corriveau RA ADRD Summit 2019 Report to the National Advisory Neurological Disorders and Stroke Council. https:\/\/www.ninds.nih.gov\/News-Events\/Events-Proceedings\/Events\/Alzheimers-Disease-Related-Dementias-Summit-2019 accessed 05\/13\/2020"},{"key":"1220_CR62","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1089\/neu.2018.6226","volume":"36","author":"P Selvaraj","year":"2019","unstructured":"Selvaraj P, Wen J, Tanaka M, Zhang Y (2019) Therapeutic effect of a novel fatty acid amide hydrolase inhibitor PF04457845 in the repetitive closed head injury mouse model. J Neurotrauma 36:1655\u20131669. https:\/\/doi.org\/10.1089\/neu.2018.6226","journal-title":"J Neurotrauma"},{"key":"1220_CR63","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2017.56","volume":"49","author":"JS Seo","year":"2017","unstructured":"Seo JS, Lee S, Shin JY, Hwang YJ, Cho H, Yoo SK, Kim Y, Lim S, Kim YK, Hwang EM et al (2017) Transcriptome analyses of chronic traumatic encephalopathy show alterations in protein phosphatase expression associated with tauopathy. Exp Mol Med 49:e333. https:\/\/doi.org\/10.1038\/emm.2017.56","journal-title":"Exp Mol Med"},{"key":"1220_CR64","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1089\/ars.2017.7280","volume":"30","author":"N Shin","year":"2019","unstructured":"Shin N, Kim HG, Shin HJ, Kim S, Kwon HH, Baek H, Yi MH, Zhang E, Kim JJ, Hong J et al (2019) Uncoupled endothelial nitric oxide synthase enhances p-Tau in chronic traumatic encephalopathy mouse model. Antioxid Redox Signal 30:1601\u20131620. https:\/\/doi.org\/10.1089\/ars.2017.7280","journal-title":"Antioxid Redox Signal"},{"key":"1220_CR65","doi-asserted-by":"publisher","first-page":"3493","DOI":"10.1042\/BCJ20190506","volume":"476","author":"M Sidoryk-Wegrzynowicz","year":"2019","unstructured":"Sidoryk-Wegrzynowicz M, Struzynska L (2019) Astroglial contribution to tau-dependent neurodegeneration. Biochem J 476:3493\u20133504. https:\/\/doi.org\/10.1042\/BCJ20190506","journal-title":"Biochem J"},{"key":"1220_CR66","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s40478-021-01122-9","volume":"9","author":"DH Smith","year":"2021","unstructured":"Smith DH, Dolle JP, Ameen-Ali KE, Bretzin A, Cortes E, Crary JF, Dams-O\u2019Connor K, Diaz-Arrastia R, Edlow BL, Folkerth R et al (2021) Collaborative neuropathology network characterizing outcomes of TBI (CONNECT-TBI). Acta Neuropathol Commun 9:32. https:\/\/doi.org\/10.1186\/s40478-021-01122-9","journal-title":"Acta Neuropathol Commun"},{"key":"1220_CR67","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nrneurol.2013.29","volume":"9","author":"DH Smith","year":"2013","unstructured":"Smith DH, Johnson VE, Stewart W (2013) Chronic neuropathologies of single and repetitive TBI: substrates of dementia? Nat Rev Neurol 9:211\u2013221. https:\/\/doi.org\/10.1038\/nrneurol.2013.29","journal-title":"Nat Rev Neurol"},{"key":"1220_CR68","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1111\/bpa.12505","volume":"28","author":"VD Smith","year":"2018","unstructured":"Smith VD, Bachstetter AD, Ighodaro E, Roberts K, Abner EL, Fardo DW, Nelson PT (2018) Overlapping but distinct TDP-43 and tau pathologic patterns in aged hippocampi. Brain Pathol 28:264\u2013273. https:\/\/doi.org\/10.1111\/bpa.12505","journal-title":"Brain Pathol"},{"key":"1220_CR69","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1093\/brain\/awx350","volume":"141","author":"CA Tagge","year":"2018","unstructured":"Tagge CA, Fisher AM, Minaeva OV, Gaudreau-Balderrama A, Moncaster JA, Zhang XL, Wojnarowicz MW, Casey N, Lu H, Kokiko-Cochran ON et al (2018) Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model. Brain 141:422\u2013458. https:\/\/doi.org\/10.1093\/brain\/awx350","journal-title":"Brain"},{"key":"1220_CR70","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1089\/neu.2017.5491","volume":"36","author":"XL Tan","year":"2019","unstructured":"Tan XL, Sun M, Brady RD, Liu S, Llanos R, Cheung S, Wright DK, Casillas-Espinosa PM, Sashindranath M, O'Brien TJ et al (2019) Transactive Response DNA-Binding Protein 43 Abnormalities after Traumatic Brain Injury. J Neurotrauma. 36:87\u201399. https:\/\/doi.org\/10.1089\/neu.2017.5491","journal-title":"J Neurotrauma."},{"key":"1220_CR71","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s40478-020-00976-9","volume":"8","author":"SJ Tang","year":"2020","unstructured":"Tang SJ, Fesharaki-Zadeh A, Takahashi H, Nies SH, Smith LM, Luo A, Chyung A, Chiasseu M, Strittmatter SM (2020) Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy. Acta Neuropathol Commun 8:96. https:\/\/doi.org\/10.1186\/s40478-020-00976-9","journal-title":"Acta Neuropathol Commun"},{"key":"1220_CR72","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1089\/neu.2010.1673","volume":"29","author":"O Thau-Zuchman","year":"2012","unstructured":"Thau-Zuchman O, Shohami E, Alexandrovich AG, Trembovler V, Leker RR (2012) The anti-inflammatory drug carprofen improves long-term outcome and induces gliogenesis after traumatic brain injury. J Neurotrauma 29:375\u2013384. https:\/\/doi.org\/10.1089\/neu.2010.1673","journal-title":"J Neurotrauma"},{"key":"1220_CR73","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.expneurol.2017.09.011","volume":"299","author":"D Wiesner","year":"2018","unstructured":"Wiesner D, Tar L, Linkus B, Chandrasekar A, Olde Heuvel F, Dupuis L, Tsao W, Wong PC, Ludolph A, Roselli F (2018) Reversible induction of TDP-43 granules in cortical neurons after traumatic injury. Exp Neurol 299:15\u201325. https:\/\/doi.org\/10.1016\/j.expneurol.2017.09.011","journal-title":"Exp Neurol"},{"key":"1220_CR74","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1001\/jamaneurol.2017.2822","volume":"74","author":"AL Woerman","year":"2017","unstructured":"Woerman AL, Patel S, Kazmi SA, Oehler A, Freyman Y, Espiritu L, Cotter R, Castaneda JA, Olson SH, Prusiner SB (2017) Kinetics of human mutant tau prion formation in the brains of 2 transgenic mouse lines. JAMA Neurol 74:1464\u20131472. https:\/\/doi.org\/10.1001\/jamaneurol.2017.2822","journal-title":"JAMA Neurol"},{"key":"1220_CR75","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s40478-021-01161-2","volume":"9","author":"X Xu","year":"2021","unstructured":"Xu X, Cowan M, Beraldo F, Schranz A, McCunn P, Geremia N, Brown Z, Patel M, Nygard KL, Khazaee R et al (2021) Repetitive mild traumatic brain injury in mice triggers a slowly developing cascade of long-term and persistent behavioral deficits and pathological changes. Acta Neuropathol Commun 9:60. https:\/\/doi.org\/10.1186\/s40478-021-01161-2","journal-title":"Acta Neuropathol Commun"},{"key":"1220_CR76","doi-asserted-by":"publisher","first-page":"11178","DOI":"10.1038\/srep11178","volume":"5","author":"Z Yang","year":"2015","unstructured":"Yang Z, Wang P, Morgan D, Lin D, Pan J, Lin F, Strang KH, Selig TM, Perez PD, Febo M et al (2015) Temporal MRI characterization, neurobiochemical and neurobehavioral changes in a mouse repetitive concussive head injury model. Sci Rep 5:11178. https:\/\/doi.org\/10.1038\/srep11178","journal-title":"Sci Rep"},{"key":"1220_CR77","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","volume":"53","author":"Y Yoshiyama","year":"2007","unstructured":"Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC, Maeda J, Suhara T, Trojanowski JQ, Lee VM (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53:337\u2013351. https:\/\/doi.org\/10.1016\/j.neuron.2007.01.010","journal-title":"Neuron"},{"key":"1220_CR78","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1038\/jcbfm.2014.247","volume":"35","author":"J Zhang","year":"2015","unstructured":"Zhang J, Teng Z, Song Y, Hu M, Chen C (2015) Inhibition of monoacylglycerol lipase prevents chronic traumatic encephalopathy-like neuropathology in a mouse model of repetitive mild closed head injury. J Cereb Blood Flow Metab 35:706. https:\/\/doi.org\/10.1038\/jcbfm.2014.247","journal-title":"J Cereb Blood Flow Metab"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-021-01220-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40478-021-01220-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-021-01220-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T20:03:19Z","timestamp":1624996999000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/s40478-021-01220-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,29]]},"references-count":78,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1220"],"URL":"https:\/\/doi.org\/10.1186\/s40478-021-01220-8","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,29]]},"assertion":[{"value":"11 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal procedures were approved by the University of Massachusetts Medical School Institutional Animal Care and Use Committee. This manuscript was prepared in adherence to the ARRIVE and PRISMA guidelines (Additional file : Supplementary information).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing financial interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"118"}}