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In Situ Detection of Inflammatory Mediators in Post Mortem Human Brain Tissue after Traumatic Injury
Abstract
Little is known about the molecular events following severe traumatic brain injury (TBI) in humans and to date there are no efficient therapies for the treatment of patients. In this study, the first of its kind in human tissue, a total of 21 post mortem trauma brain samples were analyzed. The inflammatory response within the brain tissue was explored by measuring the expression of various inflammatory cytokines at the mRNA and protein levels. These mediators were interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF). This study shows for the first time in human brain tissue that 1) pro-inflammatory mediator protein levels are significantly increased in situ following acute brain injury while anti-inflammatory cytokines protein levels remain unchanged; 2) the cerebral inflammatory response begins within minutes of acute TBI, much earlier than previously thought; 3) IL-6, IL-8, TNF-alpha, and IL-1beta mRNA levels are significantly increased following injury; 4) the rise in cytokine protein level coincides with increased levels of their mRNAs suggesting that traumatic injury elicits an immediate cerebral inflammatory response. Altogether these data confirm and extend previous observations on the release of cytokines in the cerebrospinal fluid of severe TBI patients. Finally, this study highlights the need to characterize the cell source of cytokines and elucidate their mode of action.
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“There are other studies, however, indicating that different types of neuropathology, such as neuroinflammation (36), b-amyloid deposition (37), and accumulation of TDP-43 (38) and p-tau (37, 39, 40) can and do arise following a single moderate-severe TBI (41)(42)(43), and there is emerging evidence that multiple types of neuropathology can be present following repetitive mild TBI (43,44).”
From Mild Chronic Traumatic Encephalopathy Neuropathology in People With No Known Participation in Contact Sports or History of Repetitive Neurotrauma (2019) · cites this paper as [36]
Citations
Cites
Moderate and severe traumatic brain injury in adults
Maas, A. I., Stocchetti, N., & Bullock, R. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70164-9 · Cited by 2,123
Pathophysiology of traumatic brain injury
Werner, C., & Engelhard, K. (2007) · British Journal of Anaesthesia · doi:10.1093/bja/aem131 · Cited by 1,712
The role of inflammation in CNS injury and disease
Lucas, S., Rothwell, N. J., & Gibson, R. M. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706400 · Cited by 1,272
Clinical trials in head injury
Narayan, R. K., Michel, M. E., Ansell, B., Baethmann, A., Biegon, A., Bracken, M. B., Bullock, M. R., Choi, S. C., Clifton, G. L., Contant, C. F., et al. (2002) · Journal of Neurotrauma · doi:10.1089/089771502753754037 · Cited by 913 · cited 1×
“Despite progress in critical care, to date there are no therapies for the treatment of severe brain injuries, with mortality remaining high, up to 30% (Myburgh et al., 2008; Narayan et al., 2002).”
Woodroofe, M. N., Sarna, G. S., Wadhwa, M., Hayes, G. M., Loughlin, J., Tinker, A., & Cuzner, M. L. (1991) · Journal of Neuroimmunology · doi:10.1016/0165-5728(91)90110-s · Cited by 580
Increase in IL-6, IL-1 and TNF levels in rat brain following traumatic lesion
Taupin, V., Toulmond, S., Serrano, A., Bénavidès, J., & Zavala, F. (1993) · Journal of Neuroimmunology · doi:10.1016/0165-5728(93)90008-m · Cited by 512
Cernak, I. (2005) · NeuroRX · doi:10.1602/neurorx.2.3.410 · Cited by 462
Prognosis and Clinical Trial Design in Traumatic Brain Injury: The IMPACT Study
Maas, A., Marmarou, A., Murray, G., Teasdale, G., & Steyerberg, E. (2007) · Journal of Neurotrauma · doi:10.1089/neu.2006.0024 · Cited by 366
Closed Head Injury Triggers Early Production of TNFα and IL-6 by Brain Tissue
Shohami, E., Novikov, M., Bass, R., Yamin, A., & Gallily, R. (1994) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1994.76 · Cited by 341
ROLE OF CEREBRAL INFLAMMATION AFTER TRAUMATIC BRAIN INJURY: A REVISITED CONCEPT
Morganti-Kossmann, M. C., Rancan, M., Otto, V. I., Stahel, P. F., & Kossmann, T. (2001) · Shock · doi:10.1097/00024382-200116030-00001 · Cited by 330
Csuka, E., Morganti-Kossmann, M. C., Lenzlinger, P. M., Joller, H., Trentz, O., & Kossmann, T. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00148-4 · Cited by 325
Epidemiology and 12-month outcomes from traumatic brain injury in australia and new zealand.
Myburgh, J., Cooper, D. J., Finfer, S., Venkatesh, B., Jones, D. A., Higgins, A., Bishop, N. M., & Higlett, T. (2008) · Journal of Trauma · doi:10.1097/ta.0b013e3180340e77 · Cited by 315
Clark, R. S. B., Schiding, J. K., Kaczorowski, S. L., Marion, D. W., & Kochanek, P. M. (1994) · Journal of Neurotrauma · doi:10.1089/neu.1994.11.499 · Cited by 291
Increases in Bcl‐2 and cleavage of caspase‐1 and caspase‐3 in human brain after head injury
Clark, R. S. B., Kochanek, P. M., Chen, M., Watkins, S. C., Marion, D. W., Chen, J., Hamilton, R. L., Loeffert, J. E., & Graham, S. H. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.8.813 · Cited by 285
Kossmann, T., Stahel, P. F., Lenzlinger, P. M., Redl, H., Dubs, R. W., Trentz, O., Schlag, G., & Morganti-Kossmann, M. C. (1997) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199703000-00005 · Cited by 281
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
Kossmann, T., Hans, V., Imhof, H.-G., Stocker, R. A., Grob, P., Trentz, O., & Morganti-Kossmann, M. C. (1995) · Shock · doi:10.1097/00024382-199511000-00001 · Cited by 275
Knoblach, S. M., Fan, L., & Faden, A. I. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00273-2 · Cited by 271
Experimental brain injury induces differential expression of tumor necrosis factor-α mRNA in the CNS
Fan, L., Young, P. R., Barone, F. C., Feuerstein, G., Smith, D. H., & McIntosh, T. K. (1996) · Molecular Brain Research · doi:10.1016/0169-328x(95)00274-v · Cited by 243
CHANGES IN CSF S100B AND CYTOKINE CONCENTRATIONS IN EARLY-PHASE SEVERE TRAUMATIC BRAIN INJURY
Hayakata, T., Shiozaki, T., Tasaki, O., Ikegawa, H., Inoue, Y., Fujinaka, T., Hosotubo, H., Fuijita, K., Yamashita, T., Tanaka, H., et al. (2004) · Shock · doi:10.1097/01.shk.0000131193.80038.f1 · Cited by 242
Kossmann, T., Hans, V., Imhof, H.-G., Trentz, O., & Morganti-Kossmann, M. C. (1996) · Brain Research · doi:10.1016/0006-8993(95)01501-9 · Cited by 240
Bye, N., Habgood, M. D., Callaway, J. K., Malakooti, N., Potter, A., Kossmann, T., & Morganti-Kossmann, M. C. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.10.013 · Cited by 239
Bell, M. J., Kochanek, P. M., Doughty, L., Carcillo, J. A., Adelson, P. D., Clark, R. S. B., WISNIEWSKI, S. R., Whalen, M. J., & DeKosky, S. T. (1997) · Journal of Neurotrauma · doi:10.1089/neu.1997.14.451 · Cited by 226
Experimental brain injury induces expression of interleukin-1β mRNA in the rat brain
Fan, L., Young, P. R., Barone, F. C., Feuerstein, G., Smith, D. H., & McIntosh, T. K. (1995) · Molecular Brain Research · doi:10.1016/0169-328x(94)00287-o · Cited by 217
Merrill, J. E. (1991) · Developmental Neuroscience · doi:10.1159/000112150 · Cited by 205
Pleines, U. E., Morganti-Kossmann, M. C., Rancan, M., Joller, H., Trentz, O., & Kossmann, T. (2001) · Journal of Neurotrauma · doi:10.1089/089771501300227297 · Cited by 203
Hutchinson, P. J., O’Connell, M. T., Rothwell, N. J., Hopkins, S. J., Nortje, J., Carpenter, K. L. H., Timofeev, I. S., Al-Rawi, P. G., Menon, D. K., & Pickard, J. D. (2007) · Journal of Neurotrauma · doi:10.1089/neu.2007.0295 · Cited by 185
Raised parenchymal interleukin-6 levels correlate with improved outcome after traumatic brain injury
Winter, C. D. (2004) · Brain · doi:10.1093/brain/awh039 · Cited by 185
Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury
Whalen, M. J., Carlos, T. M., Kochanek, P. M., Wisniewski, S. R., Bell, M. J., Clark, R. S. B., DeKosky, S. T., Marion, D. W., & Adelson, D. P. (2000) · Critical Care Medicine · doi:10.1097/00003246-200004000-00003 · Cited by 175
Increased plasma and ventricular fluid interleukin-6 levels in patients with head injury.
McClain, C. J., Cohen, D. A., Phillips, R. J., Ott, L. G., & Young, B. A. (1991) · PubMed · Cited by 171
Ventricular fluid interleukin-1 activity in patients with head injury.
McClain, C. J., Cohen, D. A., Ott, L. G., Dinarello, C. A., & Young, B. A. (1987) · PubMed · Cited by 161
Kamm, K., Vanderkolk, W., Lawrence, C., Jonker, M., & Davis, A. (2004) · Journal of Trauma · doi:10.1097/01.ta.0000196345.81169.a1 · Cited by 153
Shiozaki, T., Hayakata, T., Tasaki, O., Hosotubo, H., Fuijita, K., Mouri, T., Tajima, G., Kajino, K., Nakae, H., Tanaka, H., et al. (2005) · Shock · doi:10.1097/01.shk.0000161385.62758.24 · Cited by 152
The neuroprotective role of inflammation in nervous system Injuries
Correale, J. D., & Villa, A. (2004) · Journal of Neurology · doi:10.1007/s00415-004-0649-z · Cited by 148
Morganti-Kossmann, M. C., Hans, V., Lenzlinger, P. M., Dubs, R. W., LUDWIG, E., Trentz, O., & Kossmann, T. (1999) · Journal of Neurotrauma · doi:10.1089/neu.1999.16.617 · Cited by 147
Buttram, S. D. W., Wisniewski, S. R., Jackson, E. K., Adelson, P. D., Feldman, K., Bayır, H., Berger, R. P., Clark, R. S. B., & Kochanek, P. M. (2007) · Journal of Neurotrauma · doi:10.1089/neu.2007.0349 · Cited by 143
Winter, C. D., Iannotti, F., Pringle, A. K., Trikkas, C., Clough, G. F., & Church, M. K. (2002) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(02)00153-x · Cited by 122
Hans, V., Kossmann, T., Lenzlinger, P. M., Probstmeier, R., Imhof, H.-G., Trentz, O., & Morganti-Kossmann, M. C. (1999) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199902000-00010 · Cited by 119
A Microdialysis Technique for Routine Measurement of Macromolecules in the Injured Human Brain
Hillman, J., Åneman, O., Anderson, C. D., Sjögren, F., Säberg, C., & Mellergård, P. (2005) · Neurosurgery · doi:10.1227/01.neu.0000159711.93592.8d · Cited by 113
Cell activation and inflammatory response following traumatic axonal injury in the rat
Csuka, E., Hans, V., Ammann, E., Trentz, O., Kossmann, T., & Morganti-Kossmann, M. C. (2000) · Neuroreport · doi:10.1097/00001756-200008030-00047 · Cited by 107
Temporal profile of release of interleukin-1β in neurotrauma
Fassbender, K. C., Schneider, S., Bertsch, T., Schlueter, D., Fatar, M., Ragoschke, A., Kühl, S., Kischka, U., & Hennerici, M. G. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)00977-0 · Cited by 98
Pleines, U. E., Stover, J., Kossmann, T., Trentz, O., & Morganti-Kossmann, M. C. (1998) · Journal of Neurotrauma · doi:10.1089/neu.1998.15.399 · Cited by 91
In situ detection of intracerebral cytokine expression after human brain contusion
Holmin, S., & Höjeberg, B. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.07.044 · Cited by 84
Global Road Safety Crisis Remedy Sought
Cole, T. B. (2004) · JAMA · doi:10.1001/jama.291.21.2531 · Cited by 83
Mellergård, P., Åneman, O., Sjögren, F., Pettersson, P., & Hillman, J. (2008) · Neurosurgery · doi:10.1227/01.neu.0000311072.33615.3a · Cited by 68
Chemokine detection in the cerebral tissue of patients with posttraumatic brain contusions
Stefini, R., Catenacci, E., Piva, S., Sozzani, S., Valerio, A., Bergomi, R., Cenzato, M., Mortini, P., & Latronico, N. (2008) · Journal of neurosurgery · doi:10.3171/jns/2008/108/5/0958 · Cited by 64
Folkersma, H., Brevé, J. J. P., Tilders, F. J. H., Cherian, L., Robertson, C. S., & Vandertop, W. P. (2008) · Acta Neurochirurgica · doi:10.1007/s00701-008-0151-y · Cited by 47
Tumor necrosis factor-alpha: specific binding sites in rodent brain and pituitary gland.
Wolvers, D. A. W., Marquette, C., BERKENBOSCH, F., & Haour, F. (1993) · PubMed · Cited by 46
Quantitative imaging of tyrosine hydroxylase and calmodulin in the human brain
Sutoo, D., Akiyama, K., & Yabe, K. (2001) · Journal of Neuroscience Research · doi:10.1002/1097-4547(20010301)63:5 · Cited by 17
Role of the inflammatory process in traumatic brain damage
Morganti-Kossmann, C., Satgunaseelan, L., Bye, N., Nguyen, P. N., & Kossmann, T. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9781139195805.015 · Cited by 2
Flagged first, then by citations
Research works printed but not linked: 6
- Helps Y., 2008, Injury research and statistics series number 45 (Cat no INJCAT 116)
- McClain C.J., 1987, J. Lab. Clin. Med., 110, 48
- McClain C.J, 1991, J. Lab. Clin. Med., 118, 225
- [WHO] World Health Organization, 2004, World report on traffic injury prevention
- Wolvers D.A., 1993, Eur. Cytokine Netw., 4, 377
- 10.1096/02-1067fje · DOI
Cited by
Sorted by citations
Neuroinflammation and M2 Microglia: The Good, the Bad, and the Inflamed
Cherry, J. D., Olschowka, J. A., & O’Banion, M. K. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-98 · Cited by 1,748
“weeks to months after traumatic brain injury [74-76].”
BackgroundThe 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
Traumatic Brain Injuries: Pathophysiology and Potential Therapeutic Targets
Ng, S. Y., & Lee, A. Y. W. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00528 · Cited by 906
“Analysis of cerebrospinal fluid (CSF) and post-mortem tissue of TBI patients (Buttram et al., 2007; Frugier et al., 2009; Goodman et al., 2009) and tissue of TBI rodents (Ahn et al.”
BackgroundThe Role of Markers of Inflammation in Traumatic Brain Injury
Woodcock, T. M., & Morganti-Kossmann, M. C. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00018 · Cited by 719
“Indeed, more recently we have shown that TNF mRNA and protein can be detected in post-mortem brain tissue from TBI patients that died within 17 min of injury (Frugier et al., 2010).”
BackgroundInfluentialThe 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 675
“…of Iba-1, which can occur in cases of infection or injury to the CNS. Additionally, CD68 (ED1) is also used as a marker to confirm microglial activation (Graeber et al., 1990), and CD68 immunoreactivity is observed after both mouse and human TBI (Frugier et al., 2010; Loane et al., 2014).”
Background
Metadata
- Authors
- Frugier, T., Morganti-Kossmann, M. C., O'Reilly, D., & McLean, C. A.
- Affiliations
- The Alfred Hospital (AU)
- National Trauma Research Institute, The Alfred Hospital and Department of Medicine Monash University, Melbourne, Victoria, Australia.
- Corresponding author
- Frugier, Tony
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2010-03
- Volume
- 27
- Issue
- 3
- Pages
- 497-507
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- OpenAlex
- W2084674974
- Cited by
- 278
- References
- 50
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 21 · 2023: 12 · 2022: 20 · 2021: 23 · 2020: 25 · 2019: 22 · 2018: 16 · 2017: 21 · 2016: 15 · 2015: 15 · 2014: 24 · 2013: 19 · 2012: 14
- FWCI
- 4.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurotrauma (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- traumatic brain injury, neuroinflammation, inflammatory cytokines, postmortem brain, interleukin-6, interleukin-8, TNF-α, IL-1β, cytokine mRNA expression, human brain
- MeSH terms
- Adolescent, Adult, Aged, Brain, Brain Injuries, Diagnosis, Encephalitis, Female, Humans, Interferon-gamma, Interleukins, Male, Middle Aged, RNA, Messenger, Tumor Necrosis Factor-alpha, Biomarkers, Granulocyte-Macrophage Colony-Stimulating Factor, Cytokines, Inflammation Mediators, Young Adult
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