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Child's Nervous System

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01-02-2010 | Focus Session

What has inflammation to do with traumatic brain injury?

Authors: David Cederberg, Peter Siesjö

Published in: Child's Nervous System | Issue 2/2010

Abstract

Introduction

Inflammation is an stereotypical response to tissue damage and has been extensively documented in experimental and clinical traumatic brain injury (TBI), including children.

Discussion

The initiation and orchestration of inflammation in TBI, as in other tissues, is complex and multifactorial encompassing pro- and anti-inflammatory cytokines, chemokines, adhesion molecules, complement factors, reactive oxygen and nitrogen species, and other undefined factors. It is evident that inflammation can have both beneficial and detrimental effects in TBI, but the mechanisms underlying this dichotomy are mostly unknown. Modification of the inflammatory response may be neuroprotective. Monitoring inflammation is now possible with techniques such as microdialysis; however, the prognostic value of measuring inflammatory mediators in TBI is still unclear with conflicting reports. Except for corticosteroids, no anti-inflammatory agents have been tested in TBI, and the negative results with these may have been flawed by their multiple side effects. Clinical trials with anti-inflammatory agents that target multiple or central and downstream pathways are warranted in adult and pediatric TBI. This review examines the mechanisms of inflammation after TBI, monitoring, and possible routes of intervention.

Arand M, Melzner H, Kinzl L, Brückner UB, Gebhard F (2001) Early inflammatory mediator response following isolated traumatic brain injury and other major trauma in humans. Langenbeck’s Arch Surg 386:241–248CrossRef

Auffray C, Sieweke MH, Geissmann F (2009) Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol 27:669–692CrossRefPubMed

Badie B, Schartner JM, Hagar AR, Prabakaran S, Peebles TR, Bartley B, Lapsiwala S, Resnick DK, Vorpahl J (2003) Microglia cyclooxygenase-2 activity in experimental gliomas: possible role in cerebral edema formation. Clin Cancer Res 9:872–877PubMed

Bell MJ, Kochanek PM, Doughty LA, Carcillo JA, Adelson PD, Clark RS, Whalen MJ, DeKosky ST (1997) Comparison of the interleukin-6 and interleukin-10 response in children after severe traumatic brain injury or septic shock. Acta Neurochir Suppl 70:96–97PubMed

Bellander BM, Singhrao SK, Ohlsson M, Mattsson P, Svensson M (2001) Complement activation in the human brain after traumatic head injury. J Neurotrauma 18:1295–1311CrossRefPubMed

Bruce AJ, Boling W, Kindy MS, Peschon J, Kraemer PJ, Carpenter MK, Holtsberg FW, Mattson MP (1996) Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. Nat Med 2:788–794CrossRefPubMed

Buttram SD, Wisniewski SR, Jackson EK, Adelson PD, Feldman K, Bayir H, Berger RP, Clark RS, Kochanek PM (2007) Multiplex assessment of cytokine and chemokine levels in cerebrospinal fluid following severe pediatric traumatic brain injury: effects of moderate hypothermia. J Neurotrauma 24:1707–1717CrossRefPubMed

Cernak I, O’Connor C, Vink R (2001) Activation of cyclo-oxygenase-2 contributes to motor and cognitive dysfunction following diffuse traumatic brain injury in rats. Clin Exp Pharmacol Physiol 28:922–925CrossRefPubMed

Csuka E, Morganti-Kossmann MC, Lenzlinger PM, Joller H, Trentz O, Kossmann T (1999) IL-10 levels in cerebrospinal fluid and serum of patients with severe traumatic brain injury: relationship to IL-6, TNF-alpha, TGF-beta1 and blood–brain barrier function. J Neuroimmunol 101:211–221CrossRefPubMed

10.

Dearden NM, Gibson JS, McDowall DG, Gibson RM, Cameron MM (1986) Effect of high-dose dexamethasone on outcome from severe head injury. J Neurosurg 64:81–88CrossRefPubMed

11.

Ehrlich LC, Hu S, Sheng WS, Sutton RL, Rockswold GL, Peterson PK, Chao CC (1998) Cytokine regulation of human microglial cell IL-8 production. J Immunol 160:1944–1948PubMed

12.

Fassbender K, Schneider S, Bertsch T, Schlueter D, Fatar M, Ragoschke A, Kühl S, Kischka U, Hennerici M (2000) Temporal profile of release of interleukin-1beta in neurotrauma. Neurosci Lett 284:135–138CrossRefPubMed

13.

Garcia-Segura LM, Balthazart J (2009) Steroids and neuroprotection: new advances. Front Neuroendocrinol 30:v–ixCrossRefPubMed

14.

Grzybicki D, Moore SA, Schelper R, Glabinski AR, Ransohoff RM, Murphy S (1998) Expression of monocyte chemoattractant protein (MCP-1) and nitric oxide synthase-2 following cerebral trauma. Acta Neuropathol 95:98–103CrossRefPubMed

15.

Hausmann EH, Berman NE, Wang YY, Meara JB, Wood GW, Klein RM (1998) Selective chemokine mRNA expression following brain injury. Brain Res 788:49–59CrossRefPubMed

16.

Hutchinson PJ, O’Connell MT, Rothwell NJ, Hopkins SJ, Nortje J, Carpenter KL, Timofeev I, Al-Rawi PG, Menon DK, Pickard JD (2007) Inflammation in human brain injury: intracerebral concentrations of IL-1alpha, IL-1beta, and their endogenous inhibitor IL-1ra. J Neurotrauma 24:1545–1557CrossRefPubMed

17.

Juliet PA, Mao X, Del Bigio MR (2008) Proinflammatory cytokine production by cultured neonatal rat microglia after exposure to blood products. Brain Res 1210:230–239CrossRefPubMed

18.

Kalabalikis P, Papazoglou K, Gouriotis D, Papadopoulos N, Kardara M, Papageorgiou F, Papadatos J (1999) Correlation between serum IL-6 and CRP levels and severity of head injury in children. Intensive Care Med 25:288–292CrossRefPubMed

19.

Kossmann T, Hans VH, Imhof HG, Stocker R, Grob P, Trentz O, Morganti-Kossmann C (1995) Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries. Shock 4:311–317CrossRefPubMed

20.

Leinhase I, Schmidt OI, Thurman JM, Hossini AM, Rozanski M, Taha ME, Scheffler A, John T, Smith WR, Holers VM, Stahel PF (2006) Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression, and neurological outcome after traumatic brain injury. Exp Neurol 199:454–464CrossRefPubMed

21.

Lenzlinger PM, Morganti-Kossmann MC, Laurer HL, McIntosh TK (2001) The duality of the inflammatory response to traumatic brain injury. Mol Neurobiol 24:169–181CrossRefPubMed

22.

Lloyd E, Somera-Molina K, Van Eldik LJ, Watterson DM, Wainwright MS (2008) Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury. Journal of Neuroinflammation 5:28CrossRefPubMed

23.

Longhi L, Perego C, Ortolano F, Zanier ER, Bianchi P, Stocchetti N, McIntosh TK, De Simoni MG (2009) C1-inhibitor attenuates neurobehavioral deficits and reduces contusion volume after controlled cortical impact brain injury in mice. Crit Care Med 37:659–665CrossRefPubMed

24.

Ma YL, Zhu X, Rivera PM, Tøien Ø, Barnes BM, LaManna JC, Smith MA, Drew KL (2005) Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels. Am J Physiol Regul Integr Comp Physiol 289:R1297–R1306PubMed

25.

Maier B, Schwerdtfeger K, Mautes A, Holanda M, Müller M, Steudel WI, Marzi I (2001) Differential release of interleukines 6, 8, and 10 in cerebrospinal fluid and plasma after traumatic brain injury. Shock 15:421–426CrossRefPubMed

26.

Mathew P, Graham DI, Bullock R, Maxwell W, McCulloch J, Teasdale G (1994) Focal brain injury: histological evidence of delayed inflammatory response in a new rodent model of focal cortical injury. Acta Neurochir Suppl 60:428–430

27.

McKeating EG, Andrews PJ, Signorini DF, Mascia L (1997) Transcranial cytokine gradients in patients requiring intensive care after acute brain injury. Br J Anaesth 78:520–523PubMed

28.

Moochhala SM, Lu J, Xing MC, Anuar F, Ng KC, Yang KL, Whiteman M, Atan S (2005) Mercaptoethylguanidine inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expressions induced in rats after fluid-percussion brain injury. J Trauma 59:450–457CrossRefPubMed

29.

Morganti-Kossman MC, Lenzlinger PM, Hans V, Stahel P, Csuka E, Ammann E, Stocker R, Trentz O, Kossmann T (1997) Production of cytokines following brain injury: beneficial and deleterious for the damaged tissue. Mol Psychiatry 2:133–136CrossRefPubMed

30.

Morganti-Kossmann MC, Rancan M, Otto VI, Stahel PF, Kossmann T (2001) Role of cerebral inflammation after traumatic brain injury: a revisited concept. Shock 16:165–177CrossRefPubMed

31.

Moussaieff A, Shein NA, Tsenter J, Grigoriadis S, Simeonidou C, Alexandrovich AG, Trembovler V, Ben-Neriah Y, Schmitz ML, Fiebich BL, Munoz E, Mechoulam R, Shohami E (2008) Incensole acetate: a novel neuroprotective agent isolated from Boswellia carterii. J Cereb Blood Flow Metab 28:1341–1352CrossRefPubMed

32.

Nekludov M, Antovic J, Bredbacka S, Blombäck M (2007) Coagulation abnormalities associated with severe isolated traumatic brain injury: cerebral arterio-venous differences in coagulation and inflammatory markers. J Neurotrauma 24:174–180CrossRefPubMed

33.

Rock KL, Kono H (2008) The inflammatory response to cell death. Annu Rev Pathol 3:99–126CrossRefPubMed

34.

Singhal A, Baker AJ, Hare GM, Reinders FX, Schlichter LC, Moulton RJ (2002) Association between cerebrospinal fluid interleukin-6 concentrations and outcome after severe human traumatic brain injury. J Neurotrauma 19:929–937CrossRefPubMed

35.

Sinz EH, Kochanek PM, Dixon CE, Clark RS, Carcillo JA, Schiding JK, Chen M, Wisniewski SR, Carlos TM, Williams D, DeKosky ST, Watkins SC, Marion DW, Billiar TR (1999) Inducible nitric oxide synthase is an endogenous neuroprotectant after traumatic brain injury in rats and mice. J Clin Invest 104:647–656CrossRefPubMed

36.

Stahel PF, Morganti-Kossmann MC, Kossmann T (1998) The role of the complement system in traumatic brain injury. Brain Res Brain Res Rev 27:243–256CrossRefPubMed

37.

Stefini R, Catenacci E, Piva S, Sozzani S, Valerio A, Bergomi R, Cenzato M, Mortini P, Latronico N (2008) Chemokine detection in the cerebral tissue of patients with posttraumatic brain contusions. J Neurosurg 108:958–962CrossRefPubMed

38.

Sullivan PG, Bruce-Keller AJ, Rabchevsky AG, Christakos S, Clair DK, Mattson MP, Scheff SW (1999) Exacerbation of damage and altered NF-kappaB activation in mice lacking tumor necrosis factor receptors after traumatic brain injury. J Neurosci 19:6248–6256PubMed

39.

Weil ZM, Norman GJ, DeVries AC, Nelson RJ (2008) The injured nervous system: a Darwinian perspective. Prog Neurobiol 86:48–59CrossRefPubMed

40.

Whalen MJ, Carlos TM, Kochanek PM, Wisniewski SR, Bell MJ, Clark RS, DeKosky ST, Marion DW, Adelson PD (2000) Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury. Crit Care Med 28:929–934CrossRefPubMed

41.

Winter CD, Pringle AK, Clough GF, Church MK (2004) Raised parenchymal interleukin-6 levels correlate with improved outcome after traumatic brain injury. Brain 127:315–320CrossRefPubMed

42.

You Z, Yang J, Takahashi K, Yager PH, Kim HH, Qin T, Stahl GL, Ezekowitz RA, Carroll MC, Whalen MJ (2007) Reduced tissue damage and improved recovery of motor function after traumatic brain injury in mice deficient in complement component C4. J Cereb Blood Flow Metab 27:1954–1964CrossRefPubMed

43.

Zhang X, Graham SH, Kochanek PM, Marion DW, Nathaniel PD, Watkins SC, Clark RS (2003) Caspase-8 expression and proteolysis in human brain after severe head injury. FASEB J 17:1367–1369PubMed

Title: What has inflammation to do with traumatic brain injury?
Authors: David Cederberg
Peter Siesjö
Publication date: 01-02-2010
Publisher: Springer-Verlag
Published in: Child's Nervous System / Issue 2/2010
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI: https://doi.org/10.1007/s00381-009-1029-x

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What has inflammation to do with traumatic brain injury?

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Introduction

Discussion

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Abstract

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