Inflammation and white matter degeneration persist for years after a single traumatic brain injury
Open accessAbstract
A single traumatic brain injury is associated with an increased risk of dementia and, in a proportion of patients surviving a year or more from injury, the development of hallmark Alzheimer's disease-like pathologies. However, the pathological processes linking traumatic brain injury and neurodegenerative disease remain poorly understood. Growing evidence supports a role for neuroinflammation in the development of Alzheimer's disease. In contrast, little is known about the neuroinflammatory response to brain injury and, in particular, its temporal dynamics and any potential role in neurodegeneration. Cases of traumatic brain injury with survivals ranging from 10 h to 47 years post injury (n = 52) and age-matched, uninjured control subjects (n = 44) were selected from the Glasgow Traumatic Brain Injury archive. From these, sections of the corpus callosum and adjacent parasaggital cortex were examined for microglial density and morphology, and for indices of white matter pathology and integrity. With survival of ≥3 months from injury, cases with traumatic brain injury frequently displayed extensive, densely packed, reactive microglia (CR3/43- and/or CD68-immunoreactive), a pathology not seen in control subjects or acutely injured cases. Of particular note, these reactive microglia were present in 28% of cases with survival of >1 year and up to 18 years post-trauma. In cases displaying this inflammatory pathology, evidence of ongoing white matter degradation could also be observed. Moreover, there was a 25% reduction in the corpus callosum thickness with survival >1 year post-injury. These data present striking evidence of persistent inflammation and ongoing white matter degeneration for many years after just a single traumatic brain injury in humans. Future studies to determine whether inflammation occurs in response to or, conversely, promotes white matter degeneration will be important. These findings may provide parallels for studying neurodegenerative disease, with traumatic brain injury patients serving as a model for longitudinal investigations, in particular with a view to identifying potential therapeutic interventions.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Human studies report increased mRNA expression of microglial markers OX-6 and CD68 at 1 year post-injury.
“These findings are consistent with human studies that report increased mRNA expression of microglial markers OX-6 and CD68 at 1 year post-injury (11)”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [11]
The Activated microglia and Long-term survival sections report immunohistochemical staining for CR3/43 and CD68 in human TBI cases, including persistent CD68-reactive microglia. They do not report increased mRNA expression of OX-6 or CD68 at one year post-injury; the long-term findings concern protein staining and morphology, including cases 2–8 years after injury. Page numbers are not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSeveral lines of evidence point to a relationship between single-incident TBI and AD.
“Several lines of evidence point to a relationship between single-incident TBI and AD (10, 11).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [11]
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 [102]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514 · see citing works
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208 · see citing works
Self-citationQuantification of histochemical staining by color deconvolution.
Ruifrok, A. C. C., & Johnston, D. A. (2001) · PubMed · Cited by 2,029 · 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
Axonal pathology in traumatic brain injury
Johnson, V. E., Stewart, W., & Smith, D. H. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2012.01.013 · Cited by 1,273 · see citing works
Self-citationDiffuse axonal injury in head injury: definition, diagnosis and grading
Adams, J. H., Doyle, D., Ford, I., Gennarelli, T. A., Graham, D. I., & Mclellan, D. R. (1989) · Histopathology · doi:10.1111/j.1365-2559.1989.tb03040.x · Cited by 1,176 · 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
Diffuse axonal injury due to nonmissile head injury in humans: An analysis of 45 cases
Adams, J. H., Graham, D. I., Murray, L. S., & Scott, G. (1982) · Annals of Neurology · doi:10.1002/ana.410120610 · Cited by 950 · see citing works
Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias
Plassman, B. L., Havlik, R. J., Steffens, D. C., Helms, M. J., Newman, T. N., Drosdick, D., Phillips, C., Gau, B. A., Welsh–Bohmer, K. A., Burke, J. R., et al. (2000) · Neurology · doi:10.1212/wnl.55.8.1158 · Cited by 896 · see citing works
The cellular inflammatory response in human spinal cords after injury
Fleming, J. C., Norenberg, M. D., Ramsay, D. A., Dekaban, G. A., Marcillo, A. E., Saenz, A. D., Pasquale-Styles, M., Dietrich, W. D., & Weaver, L. C. (2006) · Brain · doi:10.1093/brain/awl296 · Cited by 847 · see citing works
Fleminger, S. (2003) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.74.7.857 · Cited by 719 · see citing works
Ziebell, J. M., & Morganti-Kossmann, M. C. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2009.10.016 · Cited by 665 · see citing works
Role of Microglia in Neurotrauma
Loane, D. J., & Byrnes, K. R. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.07.002 · Cited by 657 · see citing works
Widespread tau and amyloid-beta pathology many years after a single traumatic brain injury in humans
Johnson, V. E., Stewart, W., & Smith, D. H. (2012) · Brain Pathology · doi:10.1111/j.1750-3639.2011.00513.x · Cited by 620 · see citing works
Self-citationMortimer, J. A., Van Duijn, C. M., Chandra, V, Fratiglioni, L., Graves, A. B., Heyman, A., Jorm, A. F., Kokmen, E., Kondo, K., Rocca, W. A., et al. (1991) · International Journal of Epidemiology · doi:10.1093/ije/20.supplement_2.s28 · Cited by 594 · cited 3× · see citing works
“…of active inflammation years after TBI is in a timeframe consistent with epidemiological associations linking TBI with the later onset of dementia (Mortimer et al., 1985, 1991; Graves et al., 1990; Molgaard et al., 1990; O’Meara et al., 1997; Salib and Hillier, 1997; Schofield et al., 1997; Guo…”
BackgroundTraumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease?
Johnson, V. E., Stewart, W., & Smith, D. H. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2808 · Cited by 587 · see citing works
Self-citationβ-Amyloid precursor protein (βAPP) as a marker for axonal injury after head injury
Gentleman, S. M., Nash, M. J., Sweeting, C. J., Graham, D. I., & Roberts, G. W. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90398-5 · Cited by 570 · see citing works
Head injury and the risk of AD in the MIRAGE study
Guo, Z., Cupples, L. A., Kurz, A., Auerbach, S. H., Volicer, L., Chui, H., Green, R. C., Sadovnick, A. D., Duara, R., DeCarli, C., et al. (2000) · Neurology · doi:10.1212/wnl.54.6.1316 · Cited by 506 · see citing works
The Duality of the Inflammatory Response to Traumatic Brain Injury
McIntosh, T. K., Lenzlinger, P. M., Morganti-Kossmann, M. C., & Laurer, H. L. (2001) · Molecular Neurobiology · doi:10.1385/mn:24:1-3:169 · Cited by 424 · 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
Self-citationSoares, H., Hicks, R., Smith, D., & McIntosh, T. (1995) · The Journal of Neuroscience · doi:10.1523/jneurosci.15-12-08223.1995 · Cited by 379 · see citing works
Self-citationSherriff, F. E., Bridges, L., & Sivaloganathan, S. (1994) · Acta Neuropathologica · doi:10.1007/bf00386254 · Cited by 357 · see citing works
Conde, J. R., & Streit, W. J. (2006) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/01.jnen.0000202887.22082.63 · Cited by 344 · see citing works
Tang-Schomer, M., Johnson, V., Baas, P. W., Stewart, W., & Smith, D. H. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.10.030 · Cited by 330 · see citing works
Self-citationHead injury as a risk factor for Alzheimer's disease
Mortimer, J. A., French, L., Hutton, J. T., & Schuman, L. M. (1985) · Neurology · doi:10.1212/wnl.35.2.264 · Cited by 308 · see citing works
Traumatic brain injury and time to onset of Alzheimer’s disease: a population-based study
Nemetz, P. N., Leibson, C., Naessens, J. M., Beard, M., Kokmen, E., Annegers, J. F., & Kurland, L. T. (1999) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a009724 · Cited by 295 · see citing works
Neuroinflammation is a key player in Parkinson’s disease and a prime target for therapy
Li, Q., Flood, P. M., & Hong, J. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0428-1 · Cited by 287 · see citing works
Stahel, P., Shohami, E., Younis, F. M., Kariya, K., Otto, V. I., Lenzlinger, P. M., Grosjean, M., Eugster, H., Trentz, O., Kossmann, T., et al. (2000) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1097/00004647-200002000-00019 · Cited by 279 · see citing works
Intracerebral inflammatory response to experimental brain contusion
Holmin, S., Mathiesen, T. I., Shetye, J., & Biberfeld, P. (1995) · Acta Neurochirurgica · doi:10.1007/bf01404857 · Cited by 275 · 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
Chen, X.-H., Siman, R., Iwata, A., Meaney, D. F., Trojanowski, J. Q., & Smith, D. H. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63303-2 · Cited by 271 · see citing works
Self-citationBrettschneider, J., Toledo, J. B., Van Deerlin, V. M., Elman, L., McCluskey, L., Lee, V. M.-Y., & Trojanowski, J. Q. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039216 · Cited by 268 · see citing works
Self-citationIntracerebral Inflammation after Human Brain Contusion
Holmin, S., Söderlund, J., Biberfeld, P., & Mathiesen, T. I. (1998) · Neurosurgery · doi:10.1097/00006123-199802000-00047 · Cited by 268 · see citing works
Chen, X., Johnson, V. E., Uryu, K., Trojanowski, J. Q., & Smith, D. H. (2009) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00176.x · Cited by 267 · see citing works
Self-citationSmith, D. H., Chen, X.-H., Nonaka, M., Trojanowski, J. Q., Lee, V.-Y., Saatman, K. E., Leoni, M. J., Xu, B.-N., Wolf, J. A., & Meaney, D. F. (1999) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199909000-00008 · Cited by 260 · see citing works
Self-citationAlzheimer’s disease after remote head injury: an incidence study
Schofield, P. W., Tang, M., Marder, K., Bell, K., Dooneief, G., Chun, M., Sano, M., Stern, Y., & Mayeux, R. (1997) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.62.2.119 · Cited by 260 · 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
THE ASSOCIATION BETWEEN HEAD TRAUMA AND ALZHEIMER'S DISEASE
Graves, A. B., White, E., Koepsell, T. D., Reifler, B. V., van Belle, G., Larson, E. B., & Raskind, M. A. (1990) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a115523 · Cited by 257 · see citing works
Tran, H. T., LaFerla, F. M., Holtzman, D. M., & Brody, D. L. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0858-11.2011 · Cited by 255 · see citing works
Carlos, T. M., Clark, R. S. B., Franicola-Higgins, D., Schiding, J. K., & Kochanek, P. M. (1997) · Journal of Leukocyte Biology · doi:10.1002/jlb.61.3.279 · Cited by 242 · see citing works
The Nature, Distribution and Causes of Traumatic Brain Injury
Graham, D. I., Adams, J. H., Nicoll, J. A. R., Maxwell, W., & Gennarelli, T. A. (1995) · Brain Pathology · doi:10.1111/j.1750-3639.1995.tb00618.x · Cited by 237 · see citing works
Sheng, J. G., Mrak, R. E., & Griffin, W. S. T. (1998) · Acta Neuropathologica · doi:10.1007/s004010050792 · Cited by 229 · see citing works
(1990) · PubMed Central · Cited by 214 · see citing works
Amyloid β accumulation in axons after traumatic brain injury in humans
Smith, D. H., Chen, X.-H., Iwata, A., & Graham, D. (2003) · Journal of neurosurgery · doi:10.3171/jns.2003.98.5.1072 · Cited by 196 · see citing works
Self-citationByrnes, 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
Traumatic axonal injury: practical issues for diagnosis in medicolegal cases
Geddes, J., Whitwell, H., & Graham, D. I. (2000) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.2000.026002105.x · Cited by 169 · see citing works
Nonspecific white matter degeneration following traumatic brain injury
Gale, S. D., Johnson, S. C., Bigler, E., & Blatter, D. (1995) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617700000060 · Cited by 169 · see citing works
Head Injury and Risk of Alzheimer's Disease by Apolipoprotein E Genotype
O’Meara, E. S., Kukull, W. A., Sheppard, L. A., Bowen, J., McCormick, W. C., Teri, L. L., Pfanschmidt, M. L., Thompson, J. D., Schellenberg, G. D., & Larson, E. B. (1997) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a009290 · Cited by 165 · see citing works
Prolonged 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
Distribution of β‐amyloid protein in the brain following severe head injury
Graham, D. I., Gentleman, S., Lynch, A., & Roberts, G. (1995) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1995.tb01025.x · Cited by 140 · see citing works
Brettschneider, J., Libon, D. J., Toledo, J. B., Xie, S. X., McCluskey, L. F., Elman, L. B., Geser, F., Lee, V. M. ‐., Grossman, M., & Trojanowski, J. Q. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0932-x · Cited by 140 · see citing works
Self-citationThalamic Nuclei After Human Blunt Head Injury
Maxwell, W., MacKinnon, M., Smith, D. H., McIntosh, T., & Graham, D. (2006) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/01.jnen.0000229241.28619.75 · Cited by 132 · see citing works
Self-citationThe diagnosis of diffuse axonal injury: implications for forensic practice
Geddes, J. F., Vowles, G. H., Beer, T. W., & Ellison, D. W. (1997) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1997.tb01305.x · Cited by 131 · see citing works
Engel, S., Schluesener, H. J., Mittelbronn, M. G. A., Seid, K., Adjodah, D., Wehner, H. D., & Meyermann, R. (2000) · Acta Neuropathologica · doi:10.1007/s004019900172 · Cited by 121 · see citing works
Praticò, D., & Trojanowski, J. Q. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00141-x · Cited by 116 · see citing works
Self-citationIwata, A., Chen, X., McIntosh, T. K., Browne, K. D., & Smith, D. H. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.12.1056 · Cited by 116 · see citing works
Self-citationStone, J. R., Okonkwo, D. O., Singleton, R. H., Mutlu, L. K., Helm, G. A., & Povlishock, J. T. (2002) · Journal of Neurotrauma · doi:10.1089/089771502753754073 · Cited by 101 · 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
Altered Immunoexpression of Microglia and Macrophages after Mild Head Injury
Aihara, N., Hall, J. J., Pitts, L. H., et al. (1995) · Journal of Neurotrauma · doi:10.1089/neu.1995.12.53 · Cited by 97 · see citing works
Severe Head Injury Hastens Age of Onset of Alzheimer's Disease
Gedye, A., Beattie, B. L., Tuokko, H. A., Horton, A., & Korsarek, E. (1989) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1989.tb07283.x · Cited by 90 · see citing works
CR3/43, a marker for activated human microglia: application to diagnostic neuropathology
Graeber, M. B., Bise, K., & Mehraein, P. (1994) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1994.tb00987.x · Cited by 89 · see citing works
Johnson, V. E., Stewart, W., Trojanowski, J. Q., & Smith, D. H. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0909-9 · Cited by 87 · see citing works
Tran, H. T., Sanchez, L., Esparza, T. J., & Brody, D. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025475 · Cited by 86 · see citing works
Chronic ibuprofen administration worsens cognitive outcome following traumatic brain injury in rats.
Browne, K., Iwata, A., Putt, M., & Smith, D. H. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.04.008 · Cited by 80 · see citing works
Self-citationAxonal Injury Is Accentuated in the Caudal Corpus Callosum of Head-Injured Patients
Leclercq, P., McKenzie, J., Graham, D. I., & Gentleman, S. (2001) · Journal of Neurotrauma · doi:10.1089/089771501750055721 · Cited by 56 · see citing works
Epidemiology of Head Trauma and Neurocognitive Impairment in a Multi-Ethnic Population
Molgaard, C. A., Stanford, E. P., Morton, D. J., Ryden, L. A., Schubert, K. R., & Golbeck, A. L. (1991) · Neuroepidemiology · doi:10.1159/000110778 · Cited by 52 · see citing works
Head Trauma and Age of Onset of Dementia of the Alzheimer Type
Sullivan, P., Petitti, D. B., & Barbaccia, J. J. (1987) · JAMA · doi:10.1001/jama.1987.03390170045014 · Cited by 52 · see citing works
Greaves, D. R., Quinn, C. M., Seldin, M. F., & Gordon, S. (1998) · Genomics · doi:10.1006/geno.1998.5546 · Cited by 46 · see citing works
Memory and anatomical change in severe non missile traumatic brain injury: ∼1 vs. ∼8 years follow-up
Tomaiuolo, F., Bivona, U., Lerch, J. P., et al. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2012.01.008 · Cited by 43 · see citing works
Wilson, S., Raghupathi, R., Saatman, K. E., MacKinnon, M.-A., McIntosh, T. K., & Graham, D. I. (2004) · Journal of Neurotrauma · doi:10.1089/089771504322972031 · Cited by 38 · see citing works
Christensen (1997) · doi:10.1002/(sici)1099-1166(199703)12:3
Flagged first, then by citations
Research works printed but not linked: 15
- Browne KD, Iwata A, Putt ME, Smith DH. Chronic ibuprofen adminis- tration worsens cognitive outcome following TBI in rats. Exp Neurol 2006; 201: 301-7.
- Byrnes KR, Loane DJ, Stoica BA, Zhang J, Faden AI. Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after TBI. J Neuroinflammation 2012; 9: 43.
- Carlos TM, Clark RS, Franicola-Higgins D, Schiding JK, Kochanek PM. Expression of endothelial adhesion molecules and recruitment of neu- trophils after TBI in rats. J Leukoc Biol 1997; 61: 279-85.
- Gale SD, Johnson SC, Bigler ED, Blatter DD. Nonspecific white matter degeneration following TBI. J Int Neuropsychol Soc 1995; 1: 17-28.
- Gentleman SM, Leclercq PD, Moyes L, Graham DI, Smith C, Griffin WS, et al. Long-term intracerebral inflammatory response after TBI. Forensic Sci Int 2004; 146: 97-104.
- Graham DI, Adams JH, Nicoll JA, Maxwell WL, Gennarelli TA. The nature, distribution and causes of TBI. Brain Pathol 1995a; 5: 397-406.
- Johnson VE, Stewart W, Smith DH. Axonal pathology in TBI. Exp Neurol In Press.
- Lenzlinger PM, Morganti-Kossmann MC, Laurer HL, McIntosh TK. The duality of the inflammatory response to TBI. Mol Neurobiol 2001; 24: 169-81.
- Nagamoto-Combs K, McNeal DW, Morecraft RJ, Combs CK. Prolonged microgliosis in the rhesus monkey central nervous system after TBI. J Neurotrauma 2007; 24: 1719-42.
- Ramlackhansingh AF, Brooks DJ, Greenwood RJ, Bose SK, Turkheimer FE, Kinnunen KM, et al. Inflammation after trauma: micro- glial activation and TBI. Ann Neurol 2011; 70: 374-83.
- Salib E, Hillier V. Head injury and the risk of Alzheimer's disease: a case control study. Int J Geriatr Psychiatry 1997; 12: 363-8.
- Smith DH, Chen XH, Iwata A, Graham DI. Amyloid beta accumulation in axons after TBI in humans. J Neurosurg 2003; 98: 1072-7.
- Soares HD, Hicks RR, Smith D, McIntosh TK. Inflammatory leukocytic recruitment and diffuse neuronal degeneration are separate patho- logical processes resulting from TBI. J Neurosci 1995; 15: 8223-33.
- Wilson S, Raghupathi R, Saatman KE, MacKinnon MA, McIntosh TK, Graham DI. Continued in situ DNA fragmentation of microglia/macro- phages in white matter weeks and months after TBI. J Neurotrauma 2004; 21: 239-50.
- Ziebell JM, Morganti-Kossmann MC. Involvement of pro-and anti-inflammatory cytokines and chemokines in the pathophysiology of TBI. Neurotherapeutics 2010; 7: 22-30.
Cited by
Sorted by citations
Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research
Maas, A. I. R., Menon, D. K., Adelson, P. D., Andelic, N., Bell, M. J., Belli, A., Bragge, P., Brazinova, A., Büki, A., Chesnut, R. M., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30371-x · Cited by 2,609 · see citing works
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
Neuroimmunology 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
Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain
Askew, K., Li, K., Olmos-Alonso, A., Garcia-Moreno, F., Liang, Y., Richardson, P., Tipton, T., Chapman, M. A., Riecken, K., Beccari, S., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.041 · Cited by 726 · see citing works
Chronic neuropathologies of single and repetitive TBI: substrates of dementia?
Smith, D. H., Johnson, V. E., & Stewart, W. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.29 · Cited by 699 · see citing works
Self-citationGlial 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
The chronic and evolving neurological consequences of traumatic brain injury
Wilson, L., Stewart, W., Dams-O'Connor, K., Diaz-Arrastia, R., Horton, L., Menon, D. K., & Polinder, S. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30279-x · Cited by 607 · see citing works
Clinical presentation of chronic traumatic encephalopathy
Stern, R. A., Daneshvar, D. H., Baugh, C. M., Seichepine, D. R., Montenigro, P. H., Riley, D. O., Fritts, N. G., Stamm, J. M., Robbins, C. A., McHale, L., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e3182a55f7f · Cited by 564 · see citing works
Loane, D. J., Kumar, A., Stoica, B. A., Cabatbat, R., & Faden, A. I. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000021 · Cited by 498 · see citing works
Microglia/Macrophage Polarization Dynamics in White Matter after Traumatic Brain Injury
Wang, G., Zhang, J., Hu, X., Zhang, L., Mao, L., Jiang, X., Liou, A. K.-F., Leak, R. K., Gao, Y., & Chen, J. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.146 · Cited by 473 · 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
Wang, G., Shi, Y., Jiang, X., Leak, R. K., Hu, X., Wu, Y., Pu, H., Li, W.-W., Tang, B., Wang, Y., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1501441112 · Cited by 376 · see citing works
Traumatic Brain Injury: Mechanistic Insight on Pathophysiology and Potential Therapeutic Targets
Thapa, K., Khan, H., Singh, T. G., & Kaur, A. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-021-01841-7 · Cited by 341 · see citing works
Microglial/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
Shao, F., Wang, X., Wu, H., Wu, Q., & Zhang, J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.825086 · Cited by 250 · see citing works
Astrocyte Endfeet in Brain Function and Pathology: Open Questions
Díaz-Castro, B., Robel, S., & Mishra, A. (2023) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-091922-031205 · Cited by 238 · see citing works
Call off the dog(ma): M1/M2 polarization is concurrent following traumatic brain injury
Morganti, J. M., Riparip, L.-K., & Rosi, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0148001 · Cited by 229 · 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
Acute infarcts cause focal thinning in remote cortex via degeneration of connecting fiber tracts
Duering, M., Righart, R., Wollenweber, F. A., Zietemann, V., Gesierich, B., & Dichgans, M. (2015) · Neurology · doi:10.1212/wnl.0000000000001502 · Cited by 212 · see citing works
Hellyer, P. J., Scott, G., Shanahan, M., Sharp, D. J., & Leech, R. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4648-14.2015 · Cited by 187 · see citing works
Chronic traumatic encephalopathy - confusion and controversies
Smith, D. H., Johnson, V. E., Trojanowski, J. Q., & Stewart, W. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0114-8 · Cited by 166 · see citing works
Self-citationAging and Neurodegenerative Disease: Is the Adaptive Immune System a Friend or Foe?
Mayne, K., White, J. A., McMurran, C. E., Rivera, F. J., & de la Fuente, A. G. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.572090 · Cited by 167 · see citing works
Stein, M. B., Kessler, R. C., Heeringa, S. G., Jain, S., Campbell-Sills, L., Colpe, L. J., Fullerton, C. S., Nock, M. K., Sampson, N. A., Schoenbaum, M., et al. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.14121572 · Cited by 161 · see citing works
A porcine model of traumatic brain injury via head rotational acceleration
Cullen, D. K., Harris, J. P., Browne, K. D., Wolf, J. A., Duda, J. E., Meaney, D. F., Margulies, S. S., & Smith, D. H. (2016) · Methods in Molecular Biology · doi:10.1007/978-1-4939-3816-2_17 · Cited by 142 · see citing works
Self-citationThe 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
Targeting innate immunity for neurodegenerative disorders of the central nervous system
Andreasson, K. I., Bachstetter, A. D., Colonna, M., Ginhoux, F., Holmes, C., Lamb, B., Landreth, G., Lee, D. C., Low, D., Lynch, M. A., et al. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13667 · Cited by 126 · see citing works
Ko, J., Hemphill, M., Yang, Z., Sewell, E., Na, Y. J., Sandsmark, D. K., Haber, M., Fisher, S. A., Torre, E. A., Svane, K. C., et al. (2018) · Lab on a Chip · doi:10.1039/c8lc00672e · Cited by 89 · see citing works
Self-reported head injury and risk of late-life impairment and AD pathology in an AD center cohort
Abner, E. L., Nelson, P. T., Schmitt, F. A., Browning, S. R., Fardo, D. W., Wan, L., Jicha, G. A., Cooper, G. E., Smith, C. D., Caban-Holt, A. M., et al. (2014) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000355478 · Cited by 84 · see citing works
Extracellular Vesicle Proteins and MicroRNAs as Biomarkers for Traumatic Brain Injury
Guedes, V. A., Devoto, C., Leete, J., Sass, D., Acott, J. D., Mithani, S., & Gill, J. M. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00663 · Cited by 85 · see citing works
Military-related risk factors in female veterans and risk of dementia
Yaffe, K., Lwi, S. J., Hoang, T. D., Xia, F., Barnes, D. E., Maguen, S., & Peltz, C. B. (2019) · Neurology · doi:10.1212/wnl.0000000000006778 · Cited by 78 · see citing works
Untangling senescent and damage‐associated microglia in the aging and diseased brain
Ng, P. Y., McNeely, T. L., & Baker, D. J. (2023) · The FEBS Journal · doi:10.1111/febs.16315 · Cited by 68 · see citing works
Bennett, R. E., & Brody, D. L. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2013.3320 · Cited by 64 · see citing works
Sigma-1 receptor: a potential therapeutic target for traumatic brain injury
Shi, M., Chen, F., Chen, Z., Yang, W., Yue, S., Zhang, J., & Chen, X. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.685201 · Cited by 58 · see citing works
Bidirectional Brain-Systemic Interactions and Outcomes After TBI
Faden, A. I., Barrett, J. P., Stoica, B. A., & Henry, R. J. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2020.12.004 · Cited by 57 · see citing works
Shively, S. B., Edgerton, S. L., Iacono, D., Purohit, D. P., Qu, B.-X., Haroutunian, V., Davis, K. L., Diaz-Arrastia, R., & Perl, D. P. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1649-7 · Cited by 52 · see citing works
Kokiko-Cochran, O., Ransohoff, L., Veenstra, M., Lee, S., Saber, M., Sikora, M., Teknipp, R., Xu, G., Bemiller, S., Wilson, G., et al. (2016) · Journal of Neurotrauma · doi:10.1089/neu.2015.3970 · Cited by 49 · see citing works
Induction of miR-155 after Brain Injury Promotes Type 1 Interferon and has a Neuroprotective Effect
Harrison, E. B., Emanuel, K., Lamberty, B. G., Morsey, B. M., Li, M., Kelso, M. L., Yelamanchili, S. V., & Fox, H. S. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00228 · Cited by 48 · see citing works
Seizures are a druggable mechanistic link between TBI and subsequent tauopathy.
Alyenbaawi, H., Kanyo, R., Locskai, L. F., Kamali-Jamil, R., DuVal, M. G., Bai, Q., Wille, H., Burton, E. A., & Allison, W. T. (2021) · eLife · doi:10.7554/elife.58744 · Cited by 40 · see citing works
Acute neuroinflammation induces AIS structural plasticity in a NOX2-dependent manner
Benusa, S. D., George, N. M., Sword, B. A., DeVries, G. H., & Dupree, J. L. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0889-3 · Cited by 31 · see citing works
Elevation of oxidative stress indicators in a pilot study of plasma following traumatic brain injury
Halstrom, A., MacDonald, E., Neil, C., Arendts, G., Fatovich, D., & Fitzgerald, M. (2017) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2016.09.006 · Cited by 24 · see citing works
Meek, B. P., Hill, S., & Modirrousta, M. (2021) · Brain Injury · doi:10.1080/02699052.2020.1857837 · Cited by 16 · see citing works
- Authors
- Johnson, V. E., Stewart, J. E., Begbie, F. D., Trojanowski, J. Q., Smith, D. H., & Stewart, W.
- Affiliations
- University of Pennsylvania (US)
- Southern General Hospital (GB)
- University of Glasgow (GB)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-01
- Volume
- 136
- Issue
- 1
- Pages
- 28-42
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC3562078
- OpenAlex
- W2035408187
- Cited by
- 1,045
- References
- 71
- Citations by year
- 2026: 53 · 2025: 62 · 2024: 88 · 2023: 87 · 2022: 72 · 2021: 112 · 2020: 96 · 2019: 84 · 2018: 74 · 2017: 84 · 2016: 83 · 2015: 69 · 2014: 48 · 2013: 32 · 2012: 1
- FWCI
- 49.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- University of Glasgow
- National Institutes of Health
- National Institute on Aging (AG038911, R03AG038911)
- National Institute of Neurological Disorders and Stroke (NS-038104, R01NS038104)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- traumatic brain injury, neuroinflammation, white matter degeneration, reactive microglia, corpus callosum, long-term survival, Alzheimer's disease, dementia risk, CD68, white matter integrity, neurodegeneration
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Axons, Brain, Brain Injuries, Child, Female, Humans, Inflammation, Male, Middle Aged, Nerve Degeneration, Nerve Fibers, Myelinated, Neurons, Microglia, Diffuse Axonal Injury
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
