{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T02:50:43Z","timestamp":1783824643367,"version":"3.55.0"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R21 NS126611"],"award-info":[{"award-number":["R21 NS126611"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-024-71312-7","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T14:02:44Z","timestamp":1726149764000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Microglial process convergence onto injured axonal swellings, a human postmortem brain tissue study"],"prefix":"10.1038","volume":"14","author":[{"given":"Amanda L.","family":"Logan-Wesley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen M.","family":"Gorse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey D.","family":"Lafrenaye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,12]]},"reference":[{"key":"71312_CR1","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.3171\/2017.10.JNS17352","volume":"130","author":"MC Dewan","year":"2018","unstructured":"Dewan, M. C. et al. Estimating the global incidence of traumatic brain injury. J. Neurosurg. 130, 1080\u20131097 (2018).","journal-title":"J. Neurosurg."},{"key":"71312_CR2","unstructured":"DOD TBI Worldwide Numbers [Internet]. Military Health System. [cited 2024 May 28]. Available from: https:\/\/www.health.mil\/Military-Health-Topics\/Centers-of-Excellence\/Traumatic-Brain-Injury-Center-of-Excellence\/DOD-TBI-Worldwide-Numbers."},{"key":"71312_CR3","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.expneurol.2005.12.017","volume":"198","author":"BJ Kelley","year":"2006","unstructured":"Kelley, B. J., Farkas, O., Lifshitz, J. & Povlishock, J. T. Traumatic axonal injury in the perisomatic domain triggers ultrarapid secondary axotomy and Wallerian degeneration. Exp. Neurol. 198, 350\u2013360 (2006).","journal-title":"Exp. Neurol."},{"key":"71312_CR4","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1001\/jamaneurol.2016.3764","volume":"74","author":"JM Coughlin","year":"2017","unstructured":"Coughlin, J. M. et al. Imaging of glial cell activation and white matter integrity in brains of active and recently retired national football league players. JAMA Neurol. 74, 67\u201374 (2017).","journal-title":"JAMA Neurol."},{"key":"71312_CR5","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.nbd.2014.10.019","volume":"74","author":"JM Coughlin","year":"2015","unstructured":"Coughlin, J. M. et al. Neuroinflammation and brain atrophy in former NFL players: An in vivo multimodal imaging pilot study. Neurobiol. Dis. 74, 58\u201365 (2015).","journal-title":"Neurobiol. Dis."},{"key":"71312_CR6","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1212\/WNL.0b013e3181cff5d5","volume":"74","author":"DM Little","year":"2010","unstructured":"Little, D. M. et al. Thalamic integrity underlies executive dysfunction in traumatic brain injury. Neurology 74, 558\u2013564 (2010).","journal-title":"Neurology"},{"key":"71312_CR7","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/nan.12011","volume":"39","author":"D Boche","year":"2013","unstructured":"Boche, D., Perry, V. H. & Nicoll, J. R. Review: Activation patterns of microglia and their identification in the human brain. Neuropathol. Appl. Neurobiol. 39, 3\u201318 (2013).","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"71312_CR8","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1127708\/full","author":"KD Neumann","year":"2023","unstructured":"Neumann, K. D. et al. Microglial activation persists beyond clinical recovery following sport concussion in collegiate athletes. Front. Neurol. https:\/\/doi.org\/10.3389\/fneur.2023.1127708\/full (2023).","journal-title":"Front. Neurol."},{"key":"71312_CR9","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.3109\/02699052.2015.1018325","volume":"29","author":"A Vel\u00e1zquez","year":"2015","unstructured":"Vel\u00e1zquez, A., Ortega, M., Rojas, S., Gonz\u00e1lez-Oliv\u00e1n, F. J. & Rodr\u00edguez-Baeza, A. Widespread microglial activation in patients deceased from traumatic brain injury. Brain Inj. 29, 1126\u20131133 (2015).","journal-title":"Brain Inj."},{"key":"71312_CR10","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.1523\/JNEUROSCI.3751-14.2015","volume":"35","author":"K Baalman","year":"2015","unstructured":"Baalman, K. et al. Axon initial segment-associated microglia. J. Neurosci. 35, 2283\u20132292 (2015).","journal-title":"J. Neurosci."},{"key":"71312_CR11","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.neuroscience.2012.08.058","volume":"225","author":"T Cao","year":"2012","unstructured":"Cao, T., Thomas, T. C., Ziebell, J. M., Pauly, J. R. & Lifshitz, J. Morphological and genetic activation of microglia after diffuse traumatic brain injury in the rat. Neuroscience. 225, 65\u201375 (2012).","journal-title":"Neuroscience."},{"key":"71312_CR12","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.bbi.2016.11.001","volume":"63","author":"V Chhor","year":"2017","unstructured":"Chhor, V. et al. Role of microglia in a mouse model of paediatric traumatic brain injury. Brain Behav. Immun. 63, 197\u2013209 (2017).","journal-title":"Brain Behav. Immun."},{"key":"71312_CR13","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12953","author":"MR Grovola","year":"2021","unstructured":"Grovola, M. R. et al. Diverse changes in microglia morphology and axonal pathology during the course of 1 year after mild traumatic brain injury in pigs. Brain Pathol. https:\/\/doi.org\/10.1111\/bpa.12953 (2021).","journal-title":"Brain Pathol."},{"key":"71312_CR14","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1002\/glia.23523","volume":"66","author":"KG Witcher","year":"2018","unstructured":"Witcher, K. G. et al. Traumatic brain injury-induced neuronal damage in the somatosensory cortex causes formation of rod-shaped microglia that promote astrogliosis and persistent neuroinflammation. Glia 66, 2719\u20132736 (2018).","journal-title":"Glia"},{"key":"71312_CR15","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1002\/jemt.1119","volume":"46","author":"H Aldskogius","year":"2001","unstructured":"Aldskogius, H. Microglia in neuroregeneration. Microsc. Res. Tech. 46, 40\u201346 (2001).","journal-title":"Microsc. Res. Tech."},{"key":"71312_CR16","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1093\/brain\/awn109","volume":"132","author":"H Neumann","year":"2009","unstructured":"Neumann, H., Kotter, M. R. & Franklin, R. J. M. Debris clearance by microglia: An essential link between degeneration and regeneration. Brain J. Neurol. 132, 288\u2013295 (2009).","journal-title":"Brain J. Neurol."},{"key":"71312_CR17","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s12951-023-02255-w","volume":"22","author":"P Guan","year":"2024","unstructured":"Guan, P. et al. M2 microglia-derived exosome-loaded electroconductive hydrogel for enhancing neurological recovery after spinal cord injury. J. Nanobiotechnol. 22, 8 (2024).","journal-title":"J. Nanobiotechnol."},{"key":"71312_CR18","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.tins.2023.12.003","volume":"47","author":"S Zhao","year":"2024","unstructured":"Zhao, S., Umpierre, A. D. & Wu, L.-J. Tuning neural circuits and behaviors by microglia in the adult brain. Trends Neurosci. 47, 181\u2013194 (2024).","journal-title":"Trends Neurosci."},{"key":"71312_CR19","first-page":"156","volume":"339","author":"A Aguzzi","year":"2013","unstructured":"Aguzzi, A., Barres, B. & Bennett, M. L. Microglia: Scapegoat, saboteur or something else?. Inflammation 339, 156\u2013162 (2013).","journal-title":"Inflammation"},{"key":"71312_CR20","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1002\/ana.22455","volume":"70","author":"AF Ramlackhansingh","year":"2011","unstructured":"Ramlackhansingh, A. F. et al. Inflammation after trauma: Microglial activation and traumatic brain injury. Ann. Neurol. 70, 374\u2013383 (2011).","journal-title":"Ann. Neurol."},{"key":"71312_CR21","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3390\/brainsci7010011","volume":"7","author":"D Nizamutdinov","year":"2017","unstructured":"Nizamutdinov, D. & Shapiro, L. A. Overview of traumatic brain injury: An immunological context. Brain Sci. 7, 11 (2017).","journal-title":"Brain Sci."},{"key":"71312_CR22","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1002\/glia.22991","volume":"64","author":"KC Clark","year":"2016","unstructured":"Clark, K. C. et al. Compromised axon initial segment integrity in EAE is preceded by microglial reactivity and contact. Glia 64, 1190\u20131209 (2016).","journal-title":"Glia"},{"key":"71312_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/456857","volume":"2013","author":"UB Eyo","year":"2013","unstructured":"Eyo, U. B. & Wu, L. J. Bidirectional microglia-neuron communication in the healthy brain. Neural Plast. 2013, 1\u201310 (2013).","journal-title":"Neural Plast."},{"key":"71312_CR24","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1523\/JNEUROSCI.3279-14.2015","volume":"35","author":"UB Eyo","year":"2015","unstructured":"Eyo, U. B. et al. Modulation of microglial process convergence toward neuronal dendrites by extracellular calcium. J. Neurosci. 35, 2417\u20132422 (2015).","journal-title":"J. Neurosci."},{"key":"71312_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19205-4","author":"UB Eyo","year":"2018","unstructured":"Eyo, U. B. et al. The GluN2A subunit regulates neuronal NMDA receptor-induced microglia-neuron physical interactions. Sci. Rep. https:\/\/doi.org\/10.1038\/s41598-018-19205-4 (2018).","journal-title":"Sci. Rep."},{"key":"71312_CR26","doi-asserted-by":"publisher","first-page":"778","DOI":"10.3389\/fneur.2018.00778","volume":"9","author":"KM Gorse","year":"2018","unstructured":"Gorse, K. M. & Lafrenaye, A. D. The importance of inter-species variation in traumatic brain injury-induced alterations of microglial-axonal interactions. Front. Neurol. 9, 778 (2018).","journal-title":"Front. Neurol."},{"key":"71312_CR27","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1186\/s12974-015-0405-6","volume":"12","author":"AD Lafrenaye","year":"2015","unstructured":"Lafrenaye, A. D., Todani, M., Walker, S. A. & Povlishock, J. T. Microglia processes associate with diffusely injured axons following mild traumatic brain injury in the micro pig. J. Neuroinflamm. 12, 186 (2015).","journal-title":"J. Neuroinflamm."},{"key":"71312_CR28","doi-asserted-by":"publisher","first-page":"538","DOI":"10.4103\/1673-5374.180726","volume":"11","author":"A Lafrenaye","year":"2016","unstructured":"Lafrenaye, A. Physical interactions between activated microglia and injured axons: Do all contacts lead to phagocytosis?. Neural Regen. Res. 11, 538 (2016).","journal-title":"Neural Regen. Res."},{"key":"71312_CR29","doi-asserted-by":"crossref","unstructured":"Hu, Y. & Tao, W. Current perspectives on microglia-neuron communication in the central nervous system: Direct and indirect modes of interaction. Journal of Advanced Research [Internet]. 2024 [cited 2024 May 1]; Available from: https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2090123224000067.","DOI":"10.1016\/j.jare.2024.01.006"},{"key":"71312_CR30","first-page":"23","volume":"7","author":"SD Benusa","year":"2020","unstructured":"Benusa, S. D. & Lafrenaye, A. D. Microglial process convergence on axonal segments in health and disease. Neuroimmunol. Neuroinflamm. 7, 23\u201339 (2020).","journal-title":"Neuroimmunol. Neuroinflamm."},{"key":"71312_CR31","unstructured":"Mesfin, F. B., Gupta. N., Hays Shapshak. A. & Taylor, R. S. Diffuse axonal injury. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 May 10]. Available from: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK448102\/."},{"key":"71312_CR32","doi-asserted-by":"publisher","first-page":"3685","DOI":"10.1093\/brain\/awaa316","volume":"143","author":"NSN Graham","year":"2020","unstructured":"Graham, N. S. N. et al. Diffuse axonal injury predicts neurodegeneration after moderate\u2013severe traumatic brain injury. Brain 143, 3685\u20133698 (2020).","journal-title":"Brain"},{"key":"71312_CR33","doi-asserted-by":"publisher","first-page":"2600","DOI":"10.3390\/ijms18122600","volume":"18","author":"A Frati","year":"2017","unstructured":"Frati, A. et al. Diffuse axonal injury and oxidative stress: A comprehensive review. Int. J. Mol. Sci. 18, 2600 (2017).","journal-title":"Int. J. Mol. Sci."},{"key":"71312_CR34","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s00701-005-0674-4","volume":"148","author":"A B\u00fcki","year":"2006","unstructured":"B\u00fcki, A. & Povlishock, J. T. All roads lead to disconnection?\u2014Traumatic axonal injury revisited. Acta Neurochir. 148, 181\u2013193 (2006).","journal-title":"Acta Neurochir."},{"key":"71312_CR35","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1097\/00001199-200307000-00003","volume":"18","author":"DH Smith","year":"2003","unstructured":"Smith, D. H., Meaney, D. F. & Shull, W. H. Diffuse axonal injury in head trauma. J. Head Trauma Rehabil. 18, 307\u2013316 (2003).","journal-title":"J. Head Trauma Rehabil."},{"key":"71312_CR36","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1007\/s12024-022-00522-0","volume":"18","author":"Q Chen","year":"2022","unstructured":"Chen, Q. et al. Traumatic axonal injury: Neuropathological features, postmortem diagnostic methods, and strategies. Forensic Sci. Med. Pathol. 18, 530\u2013544 (2022).","journal-title":"Forensic Sci. Med. Pathol."},{"key":"71312_CR37","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1007\/BF00334880","volume":"86","author":"WL Maxwell","year":"1993","unstructured":"Maxwell, W. L., Watt, C., Graham, D. I. & Gennarelli, T. A. Ultrastructural evidence of axonal shearing as a result of lateral acceleration of the head in non-human primates. Acta Neuropathol. 86, 136\u2013144 (1993).","journal-title":"Acta Neuropathol."},{"key":"71312_CR38","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/S0196-0644(05)82738-6","volume":"22","author":"JT Povlishock","year":"1993","unstructured":"Povlishock, J. T. Pathobiology of traumatically induced axonal injury in animals and man. Ann. Emerg. Med. 22, 980\u2013986 (1993).","journal-title":"Ann. Emerg. Med."},{"key":"71312_CR39","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1089\/neu.1994.11.173","volume":"11","author":"CW Christman","year":"1994","unstructured":"Christman, C. W., Grady, M. S., Walker, S. A., Holloway, K. L. & Povlishock, J. T. Ultrastructural studies of diffuse axonal injury in humans. J. Neurotrauma. 11, 173\u2013186 (1994).","journal-title":"J. Neurotrauma."},{"key":"71312_CR40","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.expneurol.2004.05.022","volume":"190","author":"JR Stone","year":"2004","unstructured":"Stone, J. R. et al. Impaired axonal transport and altered axolemmal permeability occur in distinct populations of damaged axons following traumatic brain injury. Exp. Neurol. 190, 59\u201369 (2004).","journal-title":"Exp. Neurol."},{"key":"71312_CR41","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/0304-3940(93)90398-5","volume":"160","author":"SM Gentleman","year":"1993","unstructured":"Gentleman, S. M., Nash, M. J., Sweeting, C. J., Graham, D. I. & Roberts, G. W. \u03b2-Amyloid precursor protein (\u03b2APP) as a marker for axonal injury after head injury. Neurosci. Lett. 160, 139\u2013144 (1993).","journal-title":"Neurosci. Lett."},{"key":"71312_CR42","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/BF00386254","volume":"87","author":"FE Sherriff","year":"1994","unstructured":"Sherriff, F. E., Bridges, L. R. & Sivaloganathan, S. Early detection of axonal injury after human head trauma using immunocytochemistry for beta-amyloid precursor protein. Acta Neuropathol. 87, 55\u201362 (1994).","journal-title":"Acta Neuropathol."},{"key":"71312_CR43","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.brainres.2009.01.021","volume":"1263","author":"AM DiLeonardi","year":"2009","unstructured":"DiLeonardi, A. M., Huh, J. W. & Raghupathi, R. Impaired axonal transport and neurofilament compaction occur in separate populations of injured axons following diffuse brain injury in the immature rat. Brain Res. 1263, 174\u2013182 (2009).","journal-title":"Brain Res."},{"key":"71312_CR44","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1097\/00005072-199710000-00007","volume":"56","author":"HM Bramlett","year":"1997","unstructured":"Bramlett, H. M., Kraydieh, S., Green, E. J. & Dietrich, W. D. Temporal and regional patterns of axonal damage following traumatic brain injury: A beta-amyloid precursor protein immunocytochemical study in rats. J. Neuropathol. Exp. Neurol. 56, 1132\u20131141 (1997).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"71312_CR45","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/S0002-9440(10)63303-2","volume":"165","author":"X-H Chen","year":"2004","unstructured":"Chen, X.-H. et al. Long-term accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma. Am. J. Pathol. 165, 357\u2013371 (2004).","journal-title":"Am. J. Pathol."},{"key":"71312_CR46","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/j.1750-3639.2011.00513.x","volume":"22","author":"VE Johnson","year":"2012","unstructured":"Johnson, V. E., Stewart, W. & Smith, D. H. Widespread tau and amyloid-beta pathology many years after a single traumatic brain injury in humans. Brain Pathol. 22, 142\u2013149 (2012).","journal-title":"Brain Pathol."},{"key":"71312_CR47","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.expneurol.2012.01.013","volume":"246","author":"VE Johnson","year":"2013","unstructured":"Johnson, V. E., Stewart, W. & Smith, D. H. Axonal pathology in traumatic brain injury. Exp. Neurol. 246, 35\u201343 (2013).","journal-title":"Exp. Neurol."},{"key":"71312_CR48","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1016\/j.injury.2007.10.005","volume":"38","author":"MC Morganti-Kossmann","year":"2007","unstructured":"Morganti-Kossmann, M. C., Satgunaseelan, L., Bye, N. & Kossmann, T. Modulation of immune response by head injury. Injury 38, 1392\u20131400 (2007).","journal-title":"Injury"},{"key":"71312_CR49","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1097\/NEN.0b013e3181588245","volume":"66","author":"BJ Kelley","year":"2007","unstructured":"Kelley, B. J., Lifshitz, J. & Povlishock, J. T. Neuroinflammatory responses after experimental diffuse traumatic brain injury. J. Neuropathol. Exp. Neurol. 66, 989\u20131001 (2007).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"71312_CR50","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1002\/jmri.24310","volume":"39","author":"Y Zhou","year":"2014","unstructured":"Zhou, Y. et al. Characterization of thalamocortical association using amplitude and connectivity of fMRI in mild traumatic brain injury. J. Magn. Reson. Imaging 39, 1558\u20131568 (2014).","journal-title":"J. Magn. Reson. Imaging"},{"key":"71312_CR51","first-page":"608732","volume":"2012","author":"RC Mannix","year":"2012","unstructured":"Mannix, R. C. & Whalen, M. J. Traumatic brain injury, microglia, and Beta amyloid. Int. J. Alzheimer\u2019s Dis. 2012, 608732 (2012).","journal-title":"Int. J. Alzheimer\u2019s Dis."},{"key":"71312_CR52","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/nan.12006","volume":"39","author":"C Smith","year":"2013","unstructured":"Smith, C. Review: The long-term consequences of microglial activation following acute traumatic brain injury. Neuropathol. Appl. Neurobiol. 39, 35\u201344 (2013).","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"71312_CR53","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1146\/annurev.immunol.021908.132528","volume":"27","author":"RM Ransohoff","year":"2009","unstructured":"Ransohoff, R. M. & Perry, V. H. Microglial physiology: Unique stimuli, specialized responses. Annu. Rev. Immunol. 27, 119\u2013145 (2009).","journal-title":"Annu. Rev. Immunol."},{"key":"71312_CR54","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1111\/bph.13125","volume":"173","author":"IP Karve","year":"2015","unstructured":"Karve, I. P., Taylor, J. M. & Crack, P. J. The contribution of astrocytes and microglia to traumatic brain injury. Br. J. Pharmacol. 173, 692\u2013702 (2015).","journal-title":"Br. J. Pharmacol."},{"key":"71312_CR55","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.conb.2016.04.003","volume":"39","author":"TL Tay","year":"2016","unstructured":"Tay, T. L., Hagemeyer, N. & Prinz, M. The force awakens: Insights into the origin and formation of microglia. Curr. Opin. Neurobiol. 39, 30\u201337 (2016).","journal-title":"Curr. Opin. Neurobiol."},{"key":"71312_CR56","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.expneurol.2015.08.018","volume":"275","author":"DJ Loane","year":"2016","unstructured":"Loane, D. J. & Kumar, A. Microglia in the TBI brain: The good, the bad, and the dysregulated. Exp. Neurol. 275, 316\u2013327 (2016).","journal-title":"Exp. Neurol."},{"key":"71312_CR57","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s12974-023-02730-z","volume":"20","author":"MR Grovola","year":"2023","unstructured":"Grovola, M. R., von Reyn, C., Loane, D. J. & Cullen, D. K. Understanding microglial responses in large animal models of traumatic brain injury: An underutilized resource for preclinical and translational research. J. Neuroinflamm. 20, 67 (2023).","journal-title":"J. Neuroinflamm."},{"key":"71312_CR58","doi-asserted-by":"publisher","first-page":"5219","DOI":"10.1038\/s41467-021-25486-7","volume":"12","author":"R Ronzano","year":"2021","unstructured":"Ronzano, R. et al. Microglia-neuron interaction at nodes of Ranvier depends on neuronal activity through potassium release and contributes to remyelination. Nat. Commun. 12, 5219 (2021).","journal-title":"Nat. Commun."},{"key":"71312_CR59","doi-asserted-by":"publisher","first-page":"3974","DOI":"10.1523\/JNEUROSCI.4363-08.2009","volume":"29","author":"H Wake","year":"2009","unstructured":"Wake, H., Moorhouse, A. J., Jinno, S., Kohsaka, S. & Nabekura, J. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J. Neurosci. Off. J. Soc. Neurosci. 29, 3974\u20133980 (2009).","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"71312_CR60","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.neulet.2019.01.001","volume":"698","author":"JO Uweru","year":"2019","unstructured":"Uweru, J. O. & Eyo, U. B. A decade of diverse microglial-neuronal physical interactions in the brain (2008\u20132018). Neurosci. Lett. 698, 33\u201338 (2019).","journal-title":"Neurosci. Lett."},{"key":"71312_CR61","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.biopsych.2018.10.009","volume":"85","author":"MD Weber","year":"2019","unstructured":"Weber, M. D. et al. The influence of microglial elimination and repopulation on stress sensitization induced by repeated social defeat. Biol. Psychiatry 85, 667\u2013678 (2019).","journal-title":"Biol. Psychiatry"},{"key":"71312_CR62","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/1742-2094-9-31","volume":"9","author":"JC d\u2019Avila","year":"2012","unstructured":"d\u2019Avila, J. C. et al. Microglial activation induced by brain trauma is suppressed by post-injury treatment with a PARP inhibitor. J. Neuroinflamm. 9, 31 (2012).","journal-title":"J. Neuroinflamm."},{"key":"71312_CR63","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.neulet.2012.01.051","volume":"511","author":"E Siopi","year":"2012","unstructured":"Siopi, E. et al. Evaluation of late cognitive impairment and anxiety states following traumatic brain injury in mice: The effect of minocycline. Neurosci. Lett. 511, 110\u2013115 (2012).","journal-title":"Neurosci. Lett."},{"key":"71312_CR64","doi-asserted-by":"crossref","unstructured":"Henry, R. J., Ritzel, R. M., Barrett, J. P., Doran, S. J., Jiao, Y., Leach, J. B. et al. Microglial depletion with CSF1R inhibitor during chronic phase of experimental traumatic brain injury reduces neurodegeneration and neurological deficits. bioRxiv 791871 (2019).","DOI":"10.1101\/791871"},{"key":"71312_CR65","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.neuroscience.2016.01.008","volume":"318","author":"P Swiatkowski","year":"2016","unstructured":"Swiatkowski, P. et al. Activation of microglial P2Y12 receptor is required for outward potassium currents in response to neuronal injury. Neuroscience 318, 22\u201333 (2016).","journal-title":"Neuroscience"},{"key":"71312_CR66","doi-asserted-by":"publisher","first-page":"10511","DOI":"10.1523\/JNEUROSCI.0405-14.2014","volume":"34","author":"L Dissing-Olesen","year":"2014","unstructured":"Dissing-Olesen, L. et al. Activation of neuronal NMDA receptors triggers transient ATP-mediated microglial process outgrowth. J. Neurosci. 34, 10511\u201310527 (2014).","journal-title":"J. Neurosci."},{"key":"71312_CR67","doi-asserted-by":"publisher","first-page":"10528","DOI":"10.1523\/JNEUROSCI.0416-14.2014","volume":"34","author":"UB Eyo","year":"2014","unstructured":"Eyo, U. B. et al. Neuronal hyperactivity recruits microglial processes via neuronal NMDA receptors and microglial P2Y12 receptors after status epilepticus. J. Neurosci. Off. J. Soc. Neurosci. 34, 10528\u201310540 (2014).","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"71312_CR68","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.neures.2012.03.006","volume":"73","author":"ECS Franco","year":"2012","unstructured":"Franco, E. C. S., Cardoso, M. M., Gouv\u00eaia, A., Pereira, A. & Gomes-Leal, W. Modulation of microglial activation enhances neuroprotection and functional recovery derived from bone marrow mononuclear cell transplantation after cortical ischemia. Neurosci. Res. 73, 122\u2013132 (2012).","journal-title":"Neurosci. Res."},{"key":"71312_CR69","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.expneurol.2019.04.004","volume":"316","author":"LA Hanlon","year":"2019","unstructured":"Hanlon, L. A., Raghupathi, R. & Huh, J. W. Depletion of microglia immediately following traumatic brain injury in the pediatric rat: Implications for cellular and behavioral pathology. Exp. Neurol. 316, 39\u201351 (2019).","journal-title":"Exp. Neurol."},{"key":"71312_CR70","doi-asserted-by":"publisher","first-page":"106042","DOI":"10.1016\/j.nbd.2023.106042","volume":"179","author":"C Wang","year":"2023","unstructured":"Wang, C. et al. Increased level of exosomal miR-20b-5p derived from hypothermia-treated microglia promotes neurite outgrowth and synapse recovery after traumatic brain injury. Neurobiol. Dis. 179, 106042 (2023).","journal-title":"Neurobiol. Dis."},{"key":"71312_CR71","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1006\/mcne.2002.1185","volume":"21","author":"PE Batchelor","year":"2002","unstructured":"Batchelor, P. E. et al. Macrophages and microglia produce local trophic gradients that stimulate axonal sprouting toward but not beyond the wound edge. Mol. Cell. Neurosci. 21, 436\u2013453 (2002).","journal-title":"Mol. Cell. Neurosci."},{"key":"71312_CR72","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1016\/j.cell.2013.11.030","volume":"155","author":"CN Parkhurst","year":"2013","unstructured":"Parkhurst, C. N. et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155, 1596\u20131609 (2013).","journal-title":"Cell"},{"key":"71312_CR73","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1006\/nbdi.2000.0318","volume":"7","author":"KD Dougherty","year":"2000","unstructured":"Dougherty, K. D., Dreyfus, C. F. & Black, I. B. Brain-derived neurotrophic factor in astrocytes, oligodendrocytes, and microglia\/macrophages after spinal cord injury. Neurobiol. Dis. 7, 574\u2013585 (2000).","journal-title":"Neurobiol. Dis."},{"key":"71312_CR74","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1038\/s41593-019-0511-3","volume":"22","author":"YU Liu","year":"2019","unstructured":"Liu, Y. U. et al. Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling. Nat. Neurosci. 22, 1771\u20131781 (2019).","journal-title":"Nat. Neurosci."},{"key":"71312_CR75","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1016\/j.cub.2023.04.047","volume":"33","author":"K Cao","year":"2023","unstructured":"Cao, K. et al. Microglia modulate general anesthesia through P2Y12 receptor. Curr. Biol. 33, 2187-2200.e6 (2023).","journal-title":"Curr. Biol."},{"key":"71312_CR76","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/j.1750-3639.2012.00608.x","volume":"23","author":"L Schirmer","year":"2013","unstructured":"Schirmer, L., Merkler, D., K\u00f6nig, F. B., Br\u00fcck, W. & Stadelmann, C. Neuroaxonal regeneration is more pronounced in early multiple sclerosis than in traumatic brain injury lesions. Brain Pathol. 23, 2\u201312 (2013).","journal-title":"Brain Pathol."},{"key":"71312_CR77","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s004010051018","volume":"97","author":"M Oehmichen","year":"1999","unstructured":"Oehmichen, M., Theuerkauf, I. & Meissner, C. Is traumatic axonal injury (AI) associated with an early microglial activation? Application of a double-labeling technique for simultaneous detection of microglia and AI. Acta neuropathologica. 97, 491\u2013494 (1999).","journal-title":"Acta neuropathologica."},{"key":"71312_CR78","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40478-014-0153-3","volume":"2","author":"J Ryu","year":"2014","unstructured":"Ryu, J. et al. The problem of axonal injury in the brains of veterans with histories of blast exposure. Acta Neuropathol. Commun. 2, 1\u201314 (2014).","journal-title":"Acta Neuropathol. Commun."},{"key":"71312_CR79","doi-asserted-by":"publisher","first-page":"576366","DOI":"10.3389\/fneur.2021.576366","volume":"12","author":"A Biegon","year":"2021","unstructured":"Biegon, A. Considering biological sex in traumatic brain injury. Front. Neurol. 12, 576366 (2021).","journal-title":"Front. Neurol."},{"key":"71312_CR80","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s00401-024-02735-9","volume":"147","author":"H Song","year":"2024","unstructured":"Song, H. et al. Sex differences in the extent of acute axonal pathologies after experimental concussion. Acta Neuropathol. 147, 79 (2024).","journal-title":"Acta Neuropathol."},{"key":"71312_CR81","first-page":"13","volume":"7","author":"N Yanguas-Cas\u00e1s","year":"2020","unstructured":"Yanguas-Cas\u00e1s, N. Physiological sex differences in microglia and their relevance in neurological disorders. Neuroimmunol. Neuroinflamm. 7, 13\u201322 (2020).","journal-title":"Neuroimmunol. Neuroinflamm."},{"key":"71312_CR82","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1124\/jpet.120.266205","volume":"375","author":"GA Martinez-Muniz","year":"2020","unstructured":"Martinez-Muniz, G. A. & Wood, S. K. Special section on sexual dimorphism in neuroimmune cells sex differences in the inflammatory consequences of stress: Implications for pharmacotherapy. J. Pharmacol. Exp. Ther. 375, 161\u2013174 (2020).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"71312_CR83","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1002\/dneu.22569","volume":"78","author":"JW VanRyzin","year":"2018","unstructured":"VanRyzin, J. W., Pickett, L. A. & McCarthy, M. M. Microglia: Driving critical periods and sexual differentiation of the brain. Dev. Neurobiol. 78, 580\u2013592 (2018).","journal-title":"Dev. Neurobiol."},{"key":"71312_CR84","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1111\/j.1471-4159.2011.07630.x","volume":"120","author":"JM Schwarz","year":"2012","unstructured":"Schwarz, J. M., Sholar, P. W. & Bilbo, S. D. Sex differences in microglial colonization of the developing rat brain. J. Neurochem. 120, 948\u2013963 (2012).","journal-title":"J. Neurochem."},{"key":"71312_CR85","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1089\/neu.2018.6019","volume":"36","author":"SJ Doran","year":"2019","unstructured":"Doran, S. J. et al. Sex differences in acute neuroinflammation after experimental traumatic brain injury are mediated by infiltrating myeloid cells. J. Neurotrauma 36, 1040\u20131053 (2019).","journal-title":"J. Neurotrauma"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-71312-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-71312-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-71312-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T15:04:13Z","timestamp":1726153453000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-71312-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,12]]},"references-count":85,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["71312"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-71312-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-4713316\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,12]]},"assertion":[{"value":"9 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 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"}},{"value":"The current study was approved by the Virginia Commonwealth University Institutional Review Board under IRB ID HM20029279 and was determined not to be research involving human subjects as defined by DHHS and FDA regulations. The Department of Defense (DoD)\/Uniform Services University (USU) Tissue Repository also approved the use of these tissues for this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Approval for human experiments"}}],"article-number":"21369"}}