Progressive Neurodegeneration After Experimental Brain Trauma: Association With Chronic Microglial Activation
Open accessAbstract
Recent clinical studies indicate that traumatic brain injury (TBI) produces chronic and progressive neurodegenerative changes leading to late neurologic dysfunction, but little is known about the mechanisms underlying such changes. Microglial-mediated neuroinflammationis an important secondary injury mechanism after TBI. In human studies, microglial activation has been found to persist for many years after the initial brain trauma, particularly after moderate to severe TBI. In the present study, adult C57Bl/6 mice were subjected to single moderate-level controlled cortical impact and were followed up by longitudinal T2-weighted magnetic resonance imaging in combination with stereologic histologic assessment of lesion volume expansion, neuronal loss, and microglial activation for up to 1 year after TBI. Persistent microglial activation was observed in the injured cortex through 1 year after injury and was associated with progressive lesion expansion, hippocampal neurodegeneration, and loss of myelin. Notably, highly activated microglia that expressed major histocompatibility complex class II (CR3/43), CD68, and NADPH oxidase (NOX2) were detected at the margins of the expanding lesion at 1 year after injury; biochemical markers of neuroinflammation and oxidative stress were significantly elevated at this time point. These data support emerging clinical TBI findings and provide a mechanistic link between TBI-induced chronic microglial activation and progressive neurodegeneration.
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In the minutes following TBI, microglia are recruited via purinergic signaling to clear necrotic debris and adopt a phagocytic state.
“In the minutes following TBI, microglia are recruited via purinergic signaling to clear necrotic debris and adopt a phagocytic state [100,107,108].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [100]
TBI is a biphasic injury: after the mechanical primary injury, a secondary dystrophic state produces long-term dysfunction including elevated neuroinflammation due to blood-brain barrier disruption, increased oxidative stress, and persistent changes in the microglial population.
“TBI is a biphasic injury: after the mechanical primary injury, a secondary dystrophic state produces long-term dysfunction in the brain that includes elevated neuroinflammation as a result of blood-brain barrier disruption, increased oxidative stress, and persistent changes in the microglial population [100–106].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [100]
Post-injury microglia promote increased oxidative damage leading to neurodegeneration through a NOX2-dependent mechanism.
“Of recent interest is how post-injury microglia promote increased oxidative damage leading to neurodegeneration through a NOX2-dependent mechanism [100,117,118].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [100]
Microglia associated with the long-term inflammatory phenotype following TBI are commonly defined as MHC-II/CD86/Cd11b positive, with upregulated expression of NOX24, Tlr4, Trem2, CD68, Clec7a, and Stat1, and higher expression of interferon- and immune-associated signaling genes.
“Microglia associated with the long-term inflammatory phenotype following TBI are commonly defined as MHC-II/CD86/Cd11b positive, with upregulated expression of NOX24, Tlr4, Trem2, CD68, Clec7a, and Stat1, and higher expression of interferon- and immune-associated signaling genes [100,112,115,116].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [100]
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Cites
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110 · see citing works
ATP mediates rapid microglial response to local brain injury in vivo
Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., & Gan, W.-B. (2005) · Nature Neuroscience · doi:10.1038/nn1472 · Cited by 3,913 · see citing works
Kigerl, K. A., Gensel, J. C., Ankeny, D. P., Alexander, J. K., Donnelly, D. J., & Popovich, P. G. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3257-09.2009 · Cited by 2,130 · see citing works
Microglia in neurodegenerative disease
Perry, V. H., Nicoll, J. A. R., & Holmes, C. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.17 · Cited by 1,543 · see citing works
The P2Y12 receptor regulates microglial activation by extracellular nucleotides
Haynes, S. E., Hollopeter, G., Yang, G., Kurpius, D., Dailey, M. E., Gan, W.-B., & Julius, D. (2006) · Nature Neuroscience · doi:10.1038/nn1805 · Cited by 1,542 · see citing works
Hu, X.-M., Li, P.-Y., Guo, Y., Wang, H., Leak, R., Chen, S., Gao, Y.-Q., & Chen, J. (2012) · Stroke · doi:10.1161/strokeaha.112.659656 · Cited by 1,445 · see citing works
Microglial Activation and Chronic Neurodegeneration
Lull, M. E., & Block, M. L. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.05.014 · Cited by 1,047 · see citing works
Inflammation and white matter degeneration persist for years after a single traumatic brain injury
Johnson, V. E., Stewart, J. E., Begbie, F. D., Trojanowski, J. Q., Smith, D. H., & Stewart, W. (2013) · Brain · doi:10.1093/brain/aws322 · Cited by 1,045 · see citing works
Inflammation after trauma: Microglial activation and traumatic brain injury
Ramlackhansingh, A. F., Brooks, D. J., Greenwood, R. J., Bose, S. K., Turkheimer, F. E., Kinnunen, K. M., Gentleman, S., Heckemann, R. A., Gunanayagam, K., Gelosa, G., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22455 · Cited by 999 · see citing works
Heterogeneity of Microglial Activation in the Innate Immune Response in the Brain
Colton, C. A. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9164-4 · Cited by 871 · see citing works
Wu, D., Teismann, P., Tieu, K., Vila, M., Jackson-Lewis, V. R., Ischiropoulos, H., & Przedborski, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0937239100 · Cited by 634 · see citing works
Neuroinflammation after traumatic brain injury: Opportunities for therapeutic intervention
Kumar, A., & Loane, D. J. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.06.008 · Cited by 610 · see citing works
Self-citationQin, L., Liu, Y., Wang, T., Wei, S.-J., Block, M. L., Wilson, B., Liu, B., & Hong, J.-S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307657200 · Cited by 574 · see citing works
Loane, D. J., & Faden, A. I. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.09.005 · Cited by 574 · see citing works
Self-citationTranslocator protein 18 kDa (TSPO): Molecular sensor of brain injury and repair
Chen, M.-K., & Guilarte, T. R. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.12.004 · Cited by 506 · see citing works
Progressive atrophy and neuron death for one year following brain trauma in the rat
Smith, D. H., Chen, X.-H., Pierce, J. E. S., Wolf, J. A., Trojanowski, J. Q., Graham, D. I., & McIntosh, T. K. (1997) · Journal of Neurotrauma · doi:10.1089/neu.1997.14.715 · Cited by 440 · see citing works
Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS
Liao, B., Zhao, W., Beers, D. R., Henkel-Tigges, J., & Appel, S. H. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.06.011 · Cited by 438 · see citing works
Redox regulation of glial inflammatory response to lipopolysaccharide and interferonγ
Pawate, S., Shen, Q., Fan, F., & Bhat, N. R. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20180 · Cited by 428 · see citing works
Pierce, J. E. S., Smith, D. H., Trojanowski, J. Q., & McIntosh, T. K. (1998) · Neuroscience · doi:10.1016/s0306-4522(98)00142-0 · Cited by 385 · see citing works
Bendlin, B. B., Ries, M. L., Lazar, M., Alexander, A. L., Dempsey, R. J., Rowley, H. A., Sherman, J. E., & Johnson, S. C. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.04.254 · Cited by 339 · see citing works
The Multifaceted Profile of Activated Microglia
Lynch, M. A. (2009) · Molecular Neurobiology · doi:10.1007/s12035-009-8077-9 · Cited by 323 · see citing works
Fox, G. B., Fan, L., LeVasseur, R. A., & Faden, A. I. (1998) · Journal of Neurotrauma · doi:10.1089/neu.1998.15.599 · Cited by 320 · see citing works
Self-citationMcMillan, T. M., Teasdale, G. M., & Stewart, E. (2012) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2012-302746 · Cited by 315 · see citing works
Dixon, C. E., Kochanek, P. M., Yan, H. Q., Schiding, J. K., GRIFFITH, R. G., Baum, E., Marion, D. W., & DeKosky, S. T. (1999) · Journal of Neurotrauma · doi:10.1089/neu.1999.16.109 · Cited by 303 · see citing works
Activation of NADPH Oxidase in Alzheimer’s Disease Brains
Shimohama, S., Tanino, H., Kawakami, N., Okamura, N., Kodama, H., Yamaguchi, T., Hayakawa, T., Nunomura, A., Chiba, S., Perry, G., et al. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2897 · Cited by 292 · see citing works
Inhibition of NADPH Oxidase is Neuroprotective after Ischemia—Reperfusion
Chen, H., Song, Y. S., & Chan, P. H. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.47 · Cited by 286 · see citing works
Long-term intracerebral inflammatory response after traumatic brain injury
Gentleman, S. M., Leclercq, P. D., Moyes, L., Graham, D. I., Smith, C., Griffin, W. S. T., & Nicoll, J. A. R. (2004) · Forensic Science International · doi:10.1016/j.forsciint.2004.06.027 · Cited by 272 · see citing works
Qin, L., Liu, Y., Hong, J., & Crews, F. T. (2013) · Glia · doi:10.1002/glia.22479 · Cited by 271 · see citing works
Neuroinflammation – An Early Event in Both the History and Pathogenesis of Alzheimer’s Disease
Eikelenboom, P., van Exel, E. R., Hoozemans, J. J. M., Veerhuis, R., Rozemüller, A. J. M., & van Gool, W. A. (2010) · Neurodegenerative Diseases · doi:10.1159/000283480 · Cited by 259 · see citing works
Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury
Loane, D. J., Pocivavsek, A., Moussa, C. E.-H., Thompson, R., Matsuoka, Y., Faden, A. I., Rebeck, G. W., & Burns, M. P. (2009) · Nature Medicine · doi:10.1038/nm.1940 · Cited by 246 · see citing works
Self-citationKumar, A., Stoica, B. A., Sabirzhanov, B., Burns, M. P., Faden, A. I., & Loane, D. J. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.11.013 · Cited by 244 · see citing works
Self-citationMander, P. K., & Brown, G. C. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-20 · Cited by 226 · see citing works
Zhang, Q.-G., Laird, M. D., Han, D., Nguyen, K., Scott, E., Dong, Y., Dhandapani, K. M., & Brann, D. W. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034504 · Cited by 211 · see citing works
The neuroinflammatory response in humans after traumatic brain injury
Smith, C., Gentleman, S. M., Leclercq, P. D., Murray, L. S., Griffin, W. S. T., Graham, D. I., & Nicoll, J. A. R. (2012) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12008 · Cited by 208 · see citing works
Acosta, S. A., Tajiri, N., Shinozuka, K., Ishikawa, H., Grimmig, B. A., Diamond, D. M., Sanberg, P. R., Bickford, P. C., Kaneko, Y., & Borlongan, C. V. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053376 · Cited by 194 · see citing works
Gp91phox (NOX2) in classically activated microglia exacerbates traumatic brain injury
Dohi, K., Ohtaki, H., Nakamachi, T., Yofu, S., Satoh, K., Miyamoto, K., Song, D., Tsunawaki, S., Shioda, S., & Aruga, T. (2010) · Journal of Neuroinflammation · doi:10.1186/1742-2094-7-41 · Cited by 188 · see citing works
Late exercise reduces neuroinflammation and cognitive dysfunction after traumatic brain injury
Piao, C.-S., Stoica, B. A., Wu, J., Sabirzhanov, B. E., Zhao, Z., Cabatbat, R. M., Loane, D. J., & Faden, A. I. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.12.017 · Cited by 178 · see citing works
Self-citationProlonged Activation of NF-κB Following Traumatic Brain Injury in Rats
NONAKA, M., CHEN, X.-H., PIERCE, J. E. S., LEONI, M. J., McINTOSH, T. K., WOLF, J. A., & SMITH, D. H. (1999) · Journal of Neurotrauma · doi:10.1089/neu.1999.16.1023 · Cited by 176 · see citing works
Byrnes, K. R., Loane, D. J., Stoica, B. A., Zhang, J., & Faden, A. I. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-43 · Cited by 171 · see citing works
Self-citationProlonged Microgliosis in the Rhesus Monkey Central Nervous System after Traumatic Brain Injury
Nagamoto-Combs, K., McNeal, D. W., Morecraft, R. J., & Combs, C. K. (2007) · Journal of Neurotrauma · doi:10.1089/neu.2007.0377 · Cited by 156 · see citing works
Targeting microglia-mediated neurotoxicity: the potential of NOX2 inhibitors
Surace, M. J., & Block, M. L. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1015-4 · Cited by 131 · see citing works
NADPH oxidase is involved in post-ischemic brain inflammation
Chen, H., Kim, G. S., Okami, N., Narasimhan, P., & Chan, P. H. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.01.027 · Cited by 116 · see citing works
Ng, K., Mikulis, D., Glazer, J., Kabani, N., Till, C., Greenberg, G., Thompson, A., Lazinski, D., Agid, R., Colella, B., et al. (2008) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2008.07.006 · Cited by 101 · see citing works
NOX Activity Is Increased in Mild Cognitive Impairment
Bruce‐Keller, A. J., Gupta, S., Parrino, T. E., Knight, A. G., Ebenezer, P. J., Weidner, A. M., LeVine, H., Keller, J. N., & Markesbery, W. R. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2823 · Cited by 100 · see citing works
Long-term intracerebral inflammatory response after experimental focal brain injury in rat
Holmin, S., & Mathiesen, T. I. (1999) · Neuroreport · doi:10.1097/00001756-199906230-00017 · Cited by 98 · see citing works
LONGITUDINAL VOLUMETRIC CHANGES FOLLOWING TRAUMATIC BRAIN INJURY: A TENSOR BASED MORPHOMETRY STUDY
Farbota, K. D., Sodhi, A., Bendlin, B., McLaren, D., Xu, G.-F., Rowley, H., & Johnson, S. (2012) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617712000835 · Cited by 94 · see citing works
Kabadi, S. V., Stoica, B. A., Byrnes, K. R., Hanscom, M., Loane, D. J., & Faden, A. I. (2011) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.117 · Cited by 94 · see citing works
Self-citationChung, W., Chang, A. C., Kato, I., & Chang, N.-C. A. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.72.1.72 · Cited by 88 · see citing works
Emerging roles for telomerase in neuronal development and apoptosis
Mattson, M. P., & Klapper, W. (2001) · Journal of Neuroscience Research · doi:10.1002/1097-4547(20010101)63:1 · Cited by 76 · see citing works
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Neuroinflammation: The Devil Is in the Details
DiSabato, D. J., Quan, N., & Godbout, J. P. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13607 · Cited by 1,640 · see citing works
The far-reaching scope of neuroinflammation after traumatic brain injury
Simon, D. W., McGeachy, M. J., Bayır, H., Clark, R. S. B., Loane, D. J., & Kochanek, P. M. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.13 · Cited by 1,190 · see citing works
Self-citationThe neuropathology of traumatic brain injury
McKee, A. C., & Daneshvar, D. H. (2015) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52892-6.00004-0 · Cited by 829 · see citing works
Microglia in the TBI brain: The good, the bad, and the dysregulated
Loane, D. J., & Kumar, A. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.08.018 · Cited by 816 · see citing works
Self-citationNeuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift
Jassam, Y. N., Izzy, S., Whalen, M., McGavern, D. B., & El Khoury, J. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.010 · Cited by 799 · see citing works
Calcia, M., Bonsall, D. R., Bloomfield, P. S., Selvaraj, S., Barichello, T., & Howes, O. D. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4218-9 · Cited by 710 · see citing works
Blennow, K., Brody, D. L., Kochanek, P. M., Levin, H. S., McKee, A. C., Ribbers, G. M., Yaffe, K. S., & Zetterberg, H. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.84 · Cited by 665 · see citing works
The contribution of astrocytes and microglia to traumatic brain injury
Karve, I. P., Taylor, J. M., & Crack, P. J. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13125 · Cited by 651 · see citing works
Glial responses to implanted electrodes in the brain
Salatino, J. W., Ludwig, K. A., Kozai, T. D. Y., & Purcell, E. K. (2017) · Nature Biomedical Engineering · doi:10.1038/s41551-017-0154-1 · Cited by 642 · see citing works
Bramlett, H. M., & Dietrich, W. D. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2014.3352 · Cited by 554 · see citing works
Microglial Activation in Traumatic Brain Injury
Donat, C. K., Scott, G., Gentleman, S., & Sastre, M. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00208 · Cited by 489 · see citing works
Chronic impact of traumatic brain injury on outcome and quality of life: a narrative review
Stocchetti, N., & Zanier, E. R. (2016) · Critical Care · doi:10.1186/s13054-016-1318-1 · Cited by 466 · see citing works
An Inflammation-Centric View of Neurological Disease: Beyond the Neuron
Skaper, S. D., Facci, L., Zusso, M., & Giusti, P. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00072 · Cited by 461 · see citing works
Traumatic Brain Injury and Risk of Neurodegenerative Disorder
Brett, B. L., Gardner, R. C., Godbout, J. P., Dams-O’Connor, K., & Keene, C. D. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.05.025 · Cited by 439 · see citing works
NADPH oxidase in brain injury and neurodegenerative disorders
Ma, M. W., Wang, J., Zhang, Q., Wang, R., Dhandapani, K. M., Vadlamudi, R. K., & Brann, D. W. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0150-7 · Cited by 432 · see citing works
Norden, D. M., Muccigrosso, M. M., & Godbout, J. P. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.10.028 · Cited by 413 · see citing works
Witcher, K. G., Bray, C. E., Chunchai, T., Zhao, F., O'Neil, S. M., Gordillo, A. J., Campbell, W. A., McKim, D. B., Liu, X., Dziabis, J. E., et al. (2021) · The Journal of Neuroscience · doi:10.1523/jneurosci.2469-20.2020 · Cited by 387 · see citing works
Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis.
Bolte, A. C., Dutta, A. B., Hurt, M. E., Smirnov, I., Kovacs, M. A., McKee, C. A., Ennerfelt, H. E., Shapiro, D., Nguyen, B. H., Frost, E. L., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18113-4 · Cited by 357 · see citing works
Gyoneva, S., & Ransohoff, R. M. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.04.003 · Cited by 344 · see citing works
Henry, R. J., Ritzel, R. M., Barrett, J. P., Doran, S. J., Jiao, Y., Leach, J. B., Szeto, G. L., Wu, J., Stoica, B. A., Faden, A. I., et al. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.2402-19.2020 · Cited by 333 · see citing works
Self-citationMicroglial/Macrophage Polarization Dynamics following Traumatic Brain Injury
Kumar, A., Alvarez-Croda, D.-M., Stoica, B. A., Faden, A. I., & Loane, D. J. (2016) · Journal of Neurotrauma · doi:10.1089/neu.2015.4268 · Cited by 339 · see citing works
Self-citationMicroglial-derived microparticles mediate neuroinflammation after traumatic brain injury
Kumar, A., Stoica, B. A., Loane, D. J., Yang, M., Abulwerdi, G. A., Khan, N., Kumar, A., Thom, S. R., & Faden, A. I. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0819-4 · Cited by 318 · see citing works
Self-citationSexual dimorphism in the inflammatory response to traumatic brain injury
Villapol, S., Loane, D. J., & Burns, M. P. (2017) · Glia · doi:10.1002/glia.23171 · Cited by 310 · see citing works
Self-citationTraumatic Axonal Injury: Mechanisms and Translational Opportunities
Hill, C., Coleman, M., & Menon, D. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.03.002 · Cited by 312 · see citing works
Progressive inflammation‐mediated neurodegeneration after traumatic brain or spinal cord injury
Faden, A. I., Wu, J., Stoica, B. A., & Loane, D. J. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13179 · Cited by 287 · see citing works
Self-citationFaden, A. I., & Loane, D. J. (2015) · Neurotherapeutics · doi:10.1007/s13311-014-0319-5 · Cited by 245 · see citing works
Self-citationBrain-gut axis dysfunction in the pathogenesis of traumatic brain injury
Hanscom, M., Loane, D. J., & Shea‐Donohue, T. (2021) · Journal of Clinical Investigation · doi:10.1172/jci143777 · Cited by 239 · see citing works
Self-citationMicroglial repopulation resolves inflammation and promotes brain recovery after injury: RICE et al.
Rice, R. A., Pham, J., Lee, R. J., Najafi, A. R., West, B. L., & Green, K. N. (2017) · Glia · doi:10.1002/glia.23135 · Cited by 228 · see citing works
Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration
Scott, G., Zetterberg, H., Jolly, A., Cole, J. H., Simoni, S. D., Jenkins, P. O., Feeney, C., Owen, D. R., Lingford-Hughes, A. R., Howes, O. D., et al. (2017) · Brain · doi:10.1093/brain/awx339 · Cited by 228 · see citing works
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Witcher, K. G., Eiferman, D. S., & Godbout, J. P. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.002 · Cited by 222 · see citing works
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Jarrahi, A., Braun, M., Ahluwalia, M., Gupta, R. V., Wilson, M., Munie, S., Ahluwalia, P. K., Vender, J. R., Vale, F. Ĺ., Dhandapani, K. M., et al. (2020) · Biomedicines · doi:10.3390/biomedicines8100389 · Cited by 226 · see citing works
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Fehily, B., & Fitzgerald, M. (2017) · Cell Transplantation · doi:10.1177/0963689717714092 · Cited by 223 · see citing works
Kumar, A., Barrett, J. P., Alvarez-Croda, D.-M., Stoica, B. A., Faden, A. I., & Loane, D. J. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.07.158 · Cited by 213 · see citing works
Self-citationLi, Y., Ritzel, R. M., Khan, N., Cao, T., He, J., Lei, Z., Matyas, J. J., Sabirzhanov, B. E., Liu, S., Li, H., et al. (2020) · Theranostics · doi:10.7150/thno.49199 · Cited by 210 · see citing works
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Schnieder, T. P., Trencevska, I., Rosoklija, G., Stankov, A., Mann, J. J., Smiley, J., & Dwork, A. J. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000107 · Cited by 202 · see citing works
Bordt, E. A., & Polster, B. M. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.07.033 · Cited by 202 · see citing works
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Hay, J. R., Johnson, V. E., Smith, D. H., & Stewart, W. B., Jr. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044116 · Cited by 193 · see citing works
Direct Neuronal Reprogramming: Achievements, Hurdles, and New Roads to Success
Gascón, S., Masserdotti, G., Russo, G. L., & Götz, M. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.06.011 · Cited by 177 · see citing works
Doran, S. J., Ritzel, R., Glaser, E. P., Henry, R., Faden, A., & Loane, D. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2018.6019 · Cited by 154 · see citing works
Self-citationMa, E. L., Smith, A. D., Desai, N., Cheung, L., Hanscom, M., Stoica, B. A., Loane, D. J., Shea‐Donohue, T., & Faden, A. I. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.06.018 · Cited by 173 · see citing works
Self-citationOsier, N. D., & Dixon, C. E. (2016) · Frontiers in Neurology · doi:10.3389/fneur.2016.00134 · Cited by 173 · see citing works
Abdullah, A. D. I., Zhang, M., Frugier, T., Bedoui, S., Taylor, J. M., & Crack, P. J. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1354-7 · Cited by 170 · see citing works
Sen, T., Saha, P., Gupta, R. K., Foley, L. M., Jiang, T., Abakumova, O. S., Hitchens, T. K., & Sen, N. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.0718-19.2019 · Cited by 166 · see citing works
Biological links between traumatic brain injury and Parkinson’s disease
Delic, V., Beck, K. D., Pang, K. C. H., & Citron, B. A. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00924-7 · Cited by 165 · see citing works
The immunological response to traumatic brain injury
Needham, E., Helmy, A. E., Zanier, E. R., Jones, J., Coles, A. J., & Menon, D. K. (2019) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2019.04.005 · Cited by 155 · see citing works
Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation
Chu, E., Mychasiuk, R., Hibbs, M. L., & Semple, B. D. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02325-6 · Cited by 152 · see citing works
Inflammation in Traumatic Brain Injury
Postolache, T. T., Wadhawan, A., Can, A., Lowry, C. A., Woodbury, M., Makkar, H., Hoisington, A. J., Scott, A. J., Potocki, E., Benros, M. E., et al. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191150 · Cited by 150 · see citing works
Animal models of traumatic brain injury
Johnson, V. E., Meaney, D. F., Cullen, D. K., & Smith, D. H. (2015) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52892-6.00008-8 · Cited by 146 · see citing works
HIV-1 TAT-mediated microglial activation: role of mitochondrial dysfunction and defective mitophagy
Thangaraj, A., Periyasamy, P., Liao, K., Bendi, V. S., Callen, S. E., Pendyala, G., & Buch, S. J. (2018) · Autophagy · doi:10.1080/15548627.2018.1476810 · Cited by 147 · see citing works
Pathophysiological Bases of Comorbidity: Traumatic Brain Injury and Post-Traumatic Stress Disorder
Kaplan, G. B., Leite‐Morris, K. A., Wang, L., Rumbika, K. K., Heinrichs, S. C., Zeng, X., Wu, L., Arena, D. T., & Teng, Y. D. (2017) · Journal of Neurotrauma · doi:10.1089/neu.2016.4953 · Cited by 146 · see citing works
Chronic Alterations in Systemic Immune Function after Traumatic Brain Injury
Ritzel, R. M., Doran, S. J., Barrett, J. P., Henry, R. J., Ma, E. L., Faden, A. I., & Loane, D. J. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2017.5399 · Cited by 139 · see citing works
Self-citationSharma, R., Shultz, S. R., Robinson, M. J., Belli, A., Hibbs, M. L., O'Brien, T. J., & Semple, B. D. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.04.034 · Cited by 137 · see citing works
Eastman, C. L., D’Ambrosio, R., & Ganesh, T. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107907 · Cited by 137 · see citing works
Apolipoprotein E4 impairs spontaneous blood brain barrier repair following traumatic brain injury
Main, B. S., Villapol, S., Sloley, S. S., Barton, D. J., Parsadanian, M., Iweka, C. A., Stefos, K. A., McCann, M. S., Washington, P. M., Rodriguez, O. C., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0249-5 · Cited by 136 · see citing works
Traumatic Brain Injury and NADPH Oxidase: A Deep Relationship
Angeloni, C., Prata, C., Sega, F. V. D., Piperno, R., & Hrelia, S. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/370312 · Cited by 133 · see citing works
A Tilted Axis: Maladaptive Inflammation and HPA Axis Dysfunction Contribute to Consequences of TBI
Tapp, Z. M., Godbout, J. P., & Kokiko‐Cochran, O. N. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00345 · Cited by 130 · see citing works
The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease
Kokiko-Cochran, O. N., & Godbout, J. P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00672 · Cited by 128 · see citing works
Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells
Cox, C. S., Hetz, R. A., Liao, G. P., Aertker, B. M., Ewing‐Cobbs, L., Juranek, J. J., Savitz, S. I., Jackson, M. L., Romanowska-Pawliczek, A. M., Triolo, F., et al. (2016) · Stem Cells · doi:10.1002/stem.2538 · Cited by 128 · see citing works
The Polarization States of Microglia in TBI: A New Paradigm for Pharmacological Intervention
Xu, H., Wang, Z., Li, J., Wu, H., Peng, Y., Fan, L., Chen, J., Gu, C., Yan, F., Wang, L., et al. (2017) · Neural Plasticity · doi:10.1155/2017/5405104 · Cited by 128 · see citing works
Muccigrosso, M. M., Ford, J., Benner, B., Moussa, D., Burnsides, C., Fenn, A. M., Popovich, P. G., Lifshitz, J., Walker, F. R., Eiferman, D. S., et al. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.01.009 · Cited by 146 · see citing works
Yauger, Y. J., Bermudez, S., Moritz, K. E., Glaser, E. P., Stoica, B. A., & Byrnes, K. R. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1430-7 · Cited by 125 · see citing works
Self-citationBarrett, J. P., Henry, R. J., Shirey, K. A., Doran, S. J., Makarevich, O. D., Ritzel, R. M., Meadows, V. A., Vogel, S. N., Faden, A. I., Stoica, B. A., et al. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.2516-19.2020 · Cited by 126 · see citing works
Self-citationPischiutta, F., Micotti, E., Hay, J., Marongiu, I., Sammali, E., Tolomeo, D., Vegliante, G., Stocchetti, N., Forloni, G., Simoni, M. D., et al. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.11.003 · Cited by 107 · see citing works
NADPH Oxidase 2 Regulates NLRP3 Inflammasome Activation in the Brain after Traumatic Brain Injury
Ma, M. W., Wang, J., Dhandapani, K. M., & Brann, D. W. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/6057609 · Cited by 116 · see citing works
A limited capacity for microglial repopulation in the adult brain
Najafi, A. R., Crapser, J., Jiang, S., Ng, W., Mortazavi, A., West, B. L., & Green, K. N. (2018) · Glia · doi:10.1002/glia.23477 · Cited by 99 · see citing works
NADPH oxidases in traumatic brain injury – Promising therapeutic targets?
Ma, M. W., Wang, J., Dhandapani, K. M., Wang, R., & Brann, D. W. (2018) · Redox Biology · doi:10.1016/j.redox.2018.03.005 · Cited by 114 · see citing works
Osier, N. D., Carlson, S. W., DeSana, A. J., & Dixon, C. E. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2014.3680 · Cited by 109 · see citing works
The Role of NLRP3 Inflammasome in the Pathogenesis of Traumatic Brain Injury
Irrera, N., Russo, M., Pallio, G., Bitto, A., Mannino, F., Minutoli, L., Altavilla, D., & Squadrito, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176204 · Cited by 97 · see citing works
Todd, B. P., Chimenti, M. S., Luo, Z., Ferguson, P. J., Bassuk, A. G., & Newell, E. A. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02197-w · Cited by 109 · see citing works
Time-Dependent Changes in Microglia Transcriptional Networks Following Traumatic Brain Injury
Izzy, S., Liu, Q., Fang, Z., Lule, S., Wu, L., Chung, J. Y., Sarro-Schwartz, A., Brown-Whalen, A., Perner, C., Hickman, S. E., et al. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00307 · Cited by 110 · see citing works
Wu, Y., Xiong, J., He, Z., Yuan, Y., Wang, B., Xu, J., Wu, M., Zhang, S., Cai, S.-F., Zhao, J., et al. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00759-5 · Cited by 106 · see citing works
Taib, T., Leconte, C., Steenwinckel, J. V., Cho, A. H., Palmier, B., Torsello, E., Lai–Kuen, R., Onyeomah, S., Ecomard, K., Benedetto, C., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0184811 · Cited by 105 · see citing works
White matter damage after traumatic brain injury: A role for damage associated molecular patterns
Braun, M., Vaibhav, K., Saad, N., Fatima, S., Vender, J. R., Baban, B., Hoda, M. N., & Dhandapani, K. M. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.05.020 · Cited by 104 · see citing works
PARP-1 Inhibition Is Neuroprotective in the R6/2 Mouse Model of Huntington’s Disease
Cardinale, A., Paldino, E., Giampà, C., Bernardi, G., & Fusco, F. R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0134482 · Cited by 101 · see citing works
Traumatic Brain Injury as a Trigger of Neurodegeneration
Johnson, V. E., Stewart, W. B., Jr., Arena, J. D., & Smith, D. H. (2017) · Advances in neurobiology · doi:10.1007/978-3-319-57193-5_15 · Cited by 97 · see citing works
Wen, L., You, W., Wang, H., Meng, Y., Feng, J., & Yang, X. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2017.5540 · Cited by 99 · see citing works
Donat, C. K., Lopez, M. Y., Sastre, M., Baxan, N., Goldfinger, M., Seeamber, R., Müller, F., Davies, P., Hellyer, P. J., Siegkas, P., et al. (2020) · Brain · doi:10.1093/brain/awaa336 · Cited by 101 · see citing works
Lafrenaye, A. D., Todani, M., Walker, S. A., & Povlishock, J. T. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0405-6 · Cited by 98 · see citing works
Zhang, B., Bailey, W. M., McVicar, A. L., & Gensel, J. C. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.07.029 · Cited by 95 · see citing works
Augusto‐Oliveira, M., Arrifano, G. D. P., Leal-Nazaré, C. G., Santos-Sacramento, L., Lopes-Araújo, A., Royes, L. F. F., & Lopez, M. E. C. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03492-8 · Cited by 104 · see citing works
Barrett, J. P., Henry, R. J., Villapol, S., Stoica, B. A., Kumar, A., Burns, M. P., Faden, A. I., & Loane, D. J. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0843-4 · Cited by 91 · see citing works
Self-citationResolution of neuroinflammation: mechanisms and potential therapeutic option
Dokalis, N., & Prinz, M. (2019) · Seminars in Immunopathology · doi:10.1007/s00281-019-00764-1 · Cited by 87 · see citing works
Ritzel, R. M., Li, Y., Jiao, Y., Lei, Z., Doran, S. J., He, J., Shahror, R. A., Henry, R. J., Khan, R., Tan, C., et al. (2023) · Science Advances · doi:10.1126/sciadv.add1101 · Cited by 89 · see citing works
Self-citationSun, Y., Bai, L., Niu, X., Wang, Z., Yin, B., Bai, G., Zhang, D., Gan, S., Sun, C., Wang, S., et al. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.01120 · Cited by 90 · see citing works
Pesticide use and incident Parkinson's disease in a cohort of farmers and their spouses
Shrestha, S., Parks, C. G., Umbach, D. M., Richards-Barber, M., Hofmann, J. N., Chen, H., Blair, A. E., Freeman, L. E. B., & Sandler, D. P. (2020) · Environmental Research · doi:10.1016/j.envres.2020.110186 · Cited by 90 · see citing works
Neuroinflammatory mechanisms of post-traumatic epilepsy
Mukherjee, S., Arisi, G. M., Mims, K., Hollingsworth, G., O’Neil, K., & Shapiro, L. A. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01854-w · Cited by 88 · see citing works
Dementia, Depression, and Associated Brain Inflammatory Mechanisms after Spinal Cord Injury
Li, Y., Cao, T., Ritzel, R. M., He, J., Faden, A. I., & Wu, J. (2020) · Cells · doi:10.3390/cells9061420 · Cited by 84 · see citing works
Self-citationTruettner, J. S., Bramlett, H., & Dietrich, W. (2017) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1177/0271678x16680003 · Cited by 75 · see citing works
Marion, C. M., McDaniel, D. P., & Armstrong, R. C. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.113040 · Cited by 81 · see citing works
Reactive gliosis in traumatic brain injury: a comprehensive review
Amlerova, Z., Chmelová, M., Anděrová, M., & Vargová, L. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1335849 · Cited by 86 · see citing works
Collins-Praino, L. E., & Corrigan, F. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.09.027 · Cited by 95 · see citing works
Zanier, E. R., Marchesi, F., Ortolano, F., Perego, C., Arabian, M., Zoerle, T., Sammali, E., Pischiutta, F., & De Simoni, M.-G. (2016) · Journal of Neurotrauma · doi:10.1089/neu.2015.4041 · Cited by 94 · see citing works
Henry, R. J., Doran, S. J., Barrett, J. P., Meadows, V. E., Sabirzhanov, B. E., Stoica, B. A., Loane, D. J., & Faden, A. I. (2018) · Neurotherapeutics · doi:10.1007/s13311-018-0665-9 · Cited by 82 · see citing works
Self-citationLoane, D. J., Stoica, B. A., Tchantchou, F., Kumar, A., Barrett, J. P., Akintola, T., Xue, F., Conn, P. J., & Faden, A. I. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0298-6 · Cited by 81 · see citing works
Self-citationRitzel, R. M., Li, Y., He, J., Khan, N., Doran, S. J., Faden, A. I., & Wu, J. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104713 · Cited by 76 · see citing works
Self-citationThe immune system in traumatic brain injury
Plesnila, N. (2015) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2015.10.008 · Cited by 80 · see citing works
Puntambekar, S. S., Saber, M., Lamb, B. T., & Kokiko‐Cochran, O. N. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.03.033 · Cited by 78 · see citing works
LncRNA-Meg3 promotes Nlrp3-mediated microglial inflammation by targeting miR-7a-5p
Meng, J., Ding, T., Chen, Y., Long, T., Xu, Q., Lian, W.-Q., & Liu, W. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.107141 · Cited by 78 · see citing works
Wehn, A. C., Khalin, I., Duering, M., Hellal, F., Culmsee, C., Vandenabeele, P., Plesnila, N., & Terpolilli, N. A. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01236-0 · Cited by 74 · see citing works
Bray, C. E., Witcher, K. G., Adekunle-Adegbite, D., Ouviña, M., Witzel, M., Hans, E., Tapp, Z. M., Packer, J. M., Goodman, E. J., Zhao, F., et al. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.1910-21.2022 · Cited by 76 · see citing works
- Authors
- Loane, D. J., Kumar, A., Stoica, B. A., Cabatbat, R., & Faden, A. I.
- Affiliations
- University of Maryland, Baltimore (US)
- Corresponding author
- Loane, David J.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-01
- Volume
- 73
- Issue
- 1
- Pages
- 14-29
- ISSN
- 0022-3069 (ISSN-L)
- PMC
- PMC4267248
- OpenAlex
- W2067451082
- Cited by
- 498
- References
- 49
- Citations by year
- 2026: 35 · 2025: 28 · 2024: 42 · 2023: 39 · 2022: 39 · 2021: 68 · 2020: 56 · 2019: 42 · 2018: 36 · 2017: 41 · 2016: 31 · 2015: 24 · 2014: 17
- FWCI
- 15.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS037313, R01NS052568, R01NS082308)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- traumatic brain injury, progressive neurodegeneration, microglial activation, neuroinflammation, controlled cortical impact, lesion expansion, hippocampal neurodegeneration, demyelination, oxidative stress, NADPH oxidase, CD68
- MeSH terms
- Animals, Brain Injuries, Disease Models, Animal, Male, Mice, Inbred C57BL, Time Factors, Microglia, Disease Progression, Neurodegenerative Diseases, Mice
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