{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T17:48:00Z","timestamp":1769104080867,"version":"3.49.0"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T00:00:00Z","timestamp":1610928000000},"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>Repetitive closed head injury (rCHI) is commonly encountered in young athletes engaged in contact and collision sports. Traumatic brain injury (TBI) including rCHI has been reported to be an important risk factor for several tauopathies in studies of adult humans and animals. However, the link between rCHI and the progression of tau pathology in adolescents remains to be elucidated. We evaluated whether rCHI can trigger the initial acceleration of pathological tau in adolescent mice and impact the long-term outcomes post-injury. To this end, we subjected adolescent transgenic mice expressing the P301S tau mutation to mild rCHI and assessed tau hyperphosphorylation, tangle formation, markers of neuroinflammation, and behavioral deficits at 40 days post rCHI. We report that rCHI did not accelerate tau pathology and did not worsen behavioral outcomes compared to control mice. However, rCHI induced cortical and hippocampal microgliosis and corpus callosum astrocytosis in P301S mice by 40 days post-injury. In contrast, we did not find significant microgliosis or astrocytosis after rCHI in age-matched WT mice or sham-injured P301S mice. Our data suggest that neuroinflammation precedes the development of Tau pathology in this rCHI model of adolescent repetitive mild TBI.<\/jats:p>","DOI":"10.3390\/ijms22020907","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T04:55:31Z","timestamp":1611032131000},"page":"907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Repetitive Traumatic Brain Injury Causes Neuroinflammation before Tau Pathology in Adolescent P301S Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Saef","family":"Izzy","sequence":"first","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02119, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Brown-Whalen","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02119, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taha","family":"Yahya","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aliyah","family":"Sarro-Schwartz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gina","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joon Yong","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sevda","family":"Lule","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liza M.","family":"Morsett","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02119, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Alquraini","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02119, USA"},{"name":"Faculty of Clinical Pharmacy, Al Baha University, Al Baha 65779, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9633-7481","authenticated-orcid":false,"given":"Limin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne E.","family":"Hickman","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02119, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Whalen","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1498-1703","authenticated-orcid":false,"given":"Joseph","family":"El Khoury","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02119, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1542\/peds.2009-3101","article-title":"Emergency department visits for concussion in young child athletes","volume":"126","author":"Bakhos","year":"2010","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1001\/jama.2010.1487","article-title":"Reports of concussions from youth sports rise along with awareness of the problem","volume":"304","author":"Mitka","year":"2010","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1097\/JSM.0000000000000268","article-title":"Young athletes\u2019 concerns about sport-related concussion: The patient\u2019s perspective","volume":"26","author":"Stein","year":"2016","journal-title":"Clin. J. Sport Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jpeds.2017.01.048","article-title":"Attitudes and counseling practices of pediatricians regarding youth sports participation and concussion risks","volume":"184","author":"Fishman","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1056\/NEJMcp064645","article-title":"Clinical practice. Concussion","volume":"356","author":"Ropper","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nrneurol.2013.29","article-title":"Chronic neuropathologies of single and repetitive TBI: Substrates of dementia?","volume":"9","author":"Smith","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1542\/peds.2005-0994","article-title":"Pediatric sport-related concussion: A review of the clinical management of an oft-neglected population","volume":"117","author":"Kirkwood","year":"2006","journal-title":"Pediatrics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/bpa.12248","article-title":"The neuropathology of chronic traumatic encephalopathy","volume":"25","author":"McKee","year":"2015","journal-title":"Brain Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1007\/s11682-012-9164-5","article-title":"Chronic traumatic encephalopathy: Neurodegeneration following repetitive concussive and subconcussive brain trauma","volume":"6","author":"Baugh","year":"2012","journal-title":"Brain Imaging Behav."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/j.1750-3639.2011.00513.x","article-title":"Widespread tau and amyloid-beta pathology many years after a single traumatic brain injury in humans","volume":"22","author":"Johnson","year":"2012","journal-title":"Brain Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s00401-011-0909-9","article-title":"Acute and chronically increased immunoreactivity to phosphorylation-independent but not pathological TDP-43 after a single traumatic brain injury in humans","volume":"122","author":"Johnson","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1093\/brain\/awx350","article-title":"Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model","volume":"141","author":"Tagge","year":"2018","journal-title":"Brain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1365-2990.1996.tb00840.x","article-title":"Neurofibrillary tangles, but not Alzheimer-type pathology, in a young boxer","volume":"22","author":"Geddes","year":"1996","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1097\/NEN.0b013e3181a9d503","article-title":"Chronic traumatic encephalopathy in athletes: Progressive tauopathy after repetitive head injury","volume":"68","author":"McKee","year":"2009","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s004010051066","article-title":"Neuronal cytoskeletal changes are an early consequence of repetitive head injury","volume":"98","author":"Geddes","year":"1999","journal-title":"Acta Neuropathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"447","DOI":"10.3233\/JAD-180721","article-title":"Tau biology, tauopathy, traumatic brain injury, and diagnostic challenges","volume":"67","author":"Castellani","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s00401-015-1502-4","article-title":"Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank","volume":"130","author":"Bieniek","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9513","DOI":"10.1523\/JNEUROSCI.0858-11.2011","article-title":"Controlled cortical impact traumatic brain injury in 3xTg-AD mice causes acute intra-axonal amyloid-beta accumulation and independently accelerates the development of tau abnormalities","volume":"31","author":"Tran","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1089\/neu.2018.5720","article-title":"Chronic white matter degeneration, but no tau pathology at one-year post-repetitive mild traumatic brain injury in a tau transgenic model","volume":"36","author":"Mouzon","year":"2019","journal-title":"J. Neurotrauma"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"184","DOI":"10.4103\/2152-7806.147566","article-title":"The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy","volume":"5","author":"Petraglia","year":"2014","journal-title":"Surg. Neurol. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.expneurol.2015.06.003","article-title":"Repetitive head trauma, chronic traumatic encephalopathy and tau: Challenges in translating from mice to men","volume":"275","author":"Ojo","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.ajpath.2015.11.006","article-title":"Dendritic spine loss and chronic white matter inflammation in a mouse model of highly repetitive head trauma","volume":"186","author":"Winston","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/NEN.0b013e3182814cdf","article-title":"Repetitive mild traumatic brain injury augments tau pathology and glial activation in aged hTau mice","volume":"72","author":"Ojo","year":"2013","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1089\/neu.2005.22.1134","article-title":"Enhanced neurofibrillary tangle formation, cerebral atrophy, and cognitive deficits induced by repetitive mild brain injury in a transgenic tauopathy mouse model","volume":"22","author":"Yoshiyama","year":"2005","journal-title":"J. Neurotrauma"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1089\/neu.2018.5700","article-title":"Repetitive concussive and subconcussive injury in a human tau mouse model results in chronic cognitive dysfunction and disruption of white matter tracts, but not tau pathology","volume":"36","author":"Gangolli","year":"2019","journal-title":"J. Neurotrauma"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.expneurol.2015.08.014","article-title":"Evidence for accelerated tauopathy in the retina of transgenic P301S tau mice exposed to repetitive mild traumatic brain injury","volume":"273","author":"Xu","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/B978-0-444-63954-7.00028-8","article-title":"The neuropathology of chronic traumatic encephalopathy","volume":"158","author":"McKee","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/ana.22455","article-title":"Inflammation after trauma: Microglial activation and traumatic brain injury","volume":"70","author":"Ramlackhansingh","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1093\/brain\/aws322","article-title":"Inflammation and white matter degeneration persist for years after a single traumatic brain injury","volume":"136","author":"Johnson","year":"2013","journal-title":"Brain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/brain\/awp264","article-title":"Stereology of cerebral cortex after traumatic brain injury matched to the Glasgow outcome score","volume":"133","author":"Maxwell","year":"2010","journal-title":"Brain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/1742-2094-9-185","article-title":"The immunology of traumatic brain injury: A prime target for Alzheimer\u2019s disease prevention","volume":"9","author":"Giunta","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9962","DOI":"10.1523\/JNEUROSCI.1898-15.2016","article-title":"Interfering with the chronic immune response rescues chronic degeneration after traumatic brain injury","volume":"36","author":"Erturk","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/s41593-018-0242-x","article-title":"Microglia in neurodegeneration","volume":"21","author":"Hickman","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"R790","DOI":"10.1016\/j.cub.2020.05.051","article-title":"Scavenger receptors","volume":"30","author":"Alquraini","year":"2020","journal-title":"Curr. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0002-9440(10)64354-4","article-title":"CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer\u2019s disease brains and can mediate production of reactive oxygen species in response to beta-amyloid fibrils","volume":"160","author":"Coraci","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.neurobiolaging.2009.02.025","article-title":"Microglia activation mediates fibrillar amyloid-beta toxicity in the aged primate cortex","volume":"32","author":"Leung","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.bbi.2020.10.015","article-title":"Lipopolysaccharide-induced sepsis-like state compromises post-ischemic neurological recovery, brain tissue survival and remodeling via mechanisms involving microvascular thrombosis and brain T cell infiltration","volume":"91","author":"Sardari","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s12974-019-1564-7","article-title":"The endotoxin hypothesis of neurodegeneration","volume":"16","author":"Brown","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.bbr.2009.12.002","article-title":"Early behavioural markers of disease in P301S tau transgenic mice","volume":"208","author":"Scattoni","year":"2010","journal-title":"Behav. Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Takeuchi, H., Iba, M., Inoue, H., Higuchi, M., Takao, K., Tsukita, K., Karatsu, Y., Iwamoto, Y., Miyakawa, T., and Suhara, T. (2011). P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021050"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Flurkey, K., Currer, M.J., and Harrison, D.E. (2007). The Mouse in Aging Research, American College Laboratory Animal Medicine (Elsevier). [2nd ed.].","DOI":"10.1016\/B978-012369454-6\/50074-1"},{"key":"ref_43","first-page":"9605265","article-title":"The appropriate marker for astrocytes: Comparing the distribution and expression of three astrocytic markers in different mouse cerebral regions","volume":"2019","author":"Zhang","year":"2019","journal-title":"Biomed. Res. Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s11916-015-0522-z","article-title":"Concussion in chronic traumatic encephalopathy","volume":"19","author":"Stein","year":"2015","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.bbrc.2016.07.123","article-title":"Amyloid-beta and tau pathology following repetitive mild traumatic brain injury","volume":"483","author":"Edwards","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1016\/j.neubiorev.2012.02.013","article-title":"Traumatic brain injury: A risk factor for Alzheimer\u2019s disease","volume":"36","author":"Sivanandam","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1089\/neu.2018.6348","article-title":"Traumatic brain injury induces tau aggregation and spreading","volume":"37","author":"Edwards","year":"2020","journal-title":"J. Neurotrauma"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"104683","DOI":"10.1016\/j.nbd.2019.104683","article-title":"Tau overexpression exacerbates neuropathology after repeated mild head impacts in male mice","volume":"134","author":"Cheng","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"113180","DOI":"10.1016\/j.expneurol.2020.113180","article-title":"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","volume":"326","author":"Bachstetter","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/1750-1326-9-55","article-title":"Merging pathology with biomechanics using CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration): A novel, surgery-free model of traumatic brain injury","volume":"9","author":"Namjoshi","year":"2014","journal-title":"Mol. Neurodegener"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.bbr.2017.04.017","article-title":"Memantine improves outcomes after repetitive traumatic brain injury","volume":"340","author":"Mei","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1177\/0271678X18786633","article-title":"Repetitive head injury in adolescent mice: A role for vascular inflammation","volume":"39","author":"Wu","year":"2019","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1474-4422(12)70291-0","article-title":"Tracking pathophysiological processes in Alzheimer\u2019s disease: An updated hypothetical model of dynamic biomarkers","volume":"12","author":"Jack","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.neuron.2017.07.010","article-title":"Neuroimmunology of traumatic brain injury: Time for a paradigm shift","volume":"95","author":"Jassam","year":"2017","journal-title":"Neuron"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3389\/fncel.2019.00307","article-title":"Time-dependent changes in microglia transcriptional networks following traumatic brain injury","volume":"13","author":"Izzy","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","article-title":"Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model","volume":"53","author":"Yoshiyama","year":"2007","journal-title":"Neuron"},{"key":"ref_57","first-page":"2740","article-title":"Microglial activation correlates in vivo with both tau and amyloid in Alzheimer\u2019s disease","volume":"141","author":"Dani","year":"2018","journal-title":"Brain"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1093\/brain\/aww017","article-title":"Early and protective microglial activation in Alzheimer\u2019s disease: A prospective study using 18F-DPA-714 PET imaging","volume":"139","author":"Hamelin","year":"2016","journal-title":"Brain"},{"key":"ref_59","first-page":"873","article-title":"Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation","volume":"26","author":"Clayton","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/jcbfm.2010.172","article-title":"Tumor necrosis factor alpha and Fas receptor contribute to cognitive deficits independent of cell death after concussive traumatic brain injury in mice","volume":"31","author":"Khuman","year":"2011","journal-title":"J. Cereb. Blood Flow. Metab."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/2\/907\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:12:23Z","timestamp":1760159543000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/2\/907"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,18]]},"references-count":60,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["ijms22020907"],"URL":"https:\/\/doi.org\/10.3390\/ijms22020907","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,18]]}}}