Skip to main content
SpringerLink
Log in

Inflammatory Process in the Pathobiology of Secondary Damage After Traumatic Brain Injury

  • Conference paper
Shock, Sepsis, and Organ Failure

Summary

The acute inflammatory process participates in the evolution of secondary damage after traumatic brain injury. Endothelial adhesion molecule upregulation, complement activation, leukocyte adhesion to cerebrovascular endothelium and invasion into brain parenchyma, microglial activation, expression of inducible nitric oxide synthase, and signaling of the neurotrophic response represent some of the components of a cybernetic, highly redundant process orchestrated by cytokines, chemoattractants and other mediators. However, the exact contribution of acute inflammation, its net impact on injury extension or cellular recovery, and the nature of the inflammatory process in specific cell types within brain parenchyma and the cerebral microcirculation all remain to be determined. Evidence supporting the participation of key components of the inflammatory cascade after traumatic brain injury in both experimental models and humans will be presented. Acute inflammation potentially contributes to a wide range of events in the pathobiology of traumatic brain injury, including; posttraumatic cerebrovascular failure, neuronal injury, neuronal protection, and recovery. Finally, the effect of moderate hypothermia on the development of the acute inflammatory response to traumatic brain injury will be discussed. Targeted manipulation of the inflammatory process after traumatic brain injury may produce novel therapeutic opportunities for this difficult but important clinical problem.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Albina J, Cui S, Mateo R, Reichner J (1993) Nitric oxide-mediated apoptosis in murine peritoneal macrophages. J Immunol 150:5080–5085

    CAS  PubMed  Google Scholar 

  • Becker P, Zieger S, Rother U et al (1987) Complement activation following severe head injury. Anaesthesist 36:301–305

    CAS  PubMed  Google Scholar 

  • Betz A, Yang G-Y, Davidson B (1995) Attenuation of stroke size in rats using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist in brain. J Cereb Blood Flow Metab 15:547–551

    Article  CAS  PubMed  Google Scholar 

  • Billiar T, Curran R, Harbrecht B et al (1990) Modulation of nitrogen oxide synthesis in vivo: NG-monomethyl-L-arginine inhibits endotoxin-induced nitrite/nitrate biosynthesis while promoting hepatic damage. J Leuk Biol 48:565–569

    CAS  Google Scholar 

  • Bohn D, Biggar W, Smith C et al (1986) Influence of hypothermia, barbiturate therapy, and intracranial pressure monitoring on morbidity and mortality after near-drowning. Crit Care Med 14:529

    Article  CAS  PubMed  Google Scholar 

  • Carlos T, Clark R, Franicola-Higgins D, Schiding JK, Kochanek PM (1995) Expression of endothelial adhesion molecules after traumatic brain injury in rats (Abstr). J Neurotrauma 12:458

    Google Scholar 

  • Chopp M, Zhang RL, Chen H, Li Y, Jiang N, Rusche JR (1994) Postischemic administration of anti-mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion. Stroke 25:869–876

    Article  CAS  PubMed  Google Scholar 

  • Clark R, Schiding JK, Kaczorowski SL, Marion DW, Kochanek PM (1994) Neutrophil accumulation after traumatic brain injury in rats: comparison of weight-drop and controlled cortical impact models. J Neurotrauma 11:499–506

    Article  CAS  PubMed  Google Scholar 

  • Clark R, Kochanek P, Brookens M et al (1995) Cerebrovascular, inflammatory cell, and neuronal inducible nitric oxide expression after trauma in immature rats. Pediatr Res 37:43A

    Google Scholar 

  • Clark R, Schiding JK, Carlos T, Bree M, DeKosky S, Kochanek P (1996a) Antibodies against mac-1 attenuate neutrophil accumulation after traumatic brain injury in rats. J Neurotrauma 13:333–341

    CAS  PubMed  Google Scholar 

  • Clark R, Kochanek P, Marion D et al (1996b) Mild posttraumatic hypothermia reduces mortality after severe controlled cortical impact in rats. J Cereb Blood Flow Metab 16:253–261

    Article  CAS  PubMed  Google Scholar 

  • Clark R, Kochanek PM, Schwarz MA et al (1996c) Inducible nitric oxide synthase expression in cerebrovascular smooth muscle and neutrophils after traumatic brain injury in immature rats. Pediatr Res 39:784–790

    Article  CAS  PubMed  Google Scholar 

  • Clark R, Kochanek P, Obrist W et al (1996d) Cerebrospinal fluid and plasma nitrite and nitrate concentrations after head injury in humans. Crit Care Med 24:1243–1251

    Article  CAS  PubMed  Google Scholar 

  • Clifton G, Jiang J, Lyeth B, Jenkins L, Hamm R, Hayes R (1991) Marked protection by moderate hypothermia after experimental traumatic brain injury. J Cereb Blood Flow Metab 11:114–121

    Article  CAS  PubMed  Google Scholar 

  • Cody R, Maris D, Seckin H, Sharar S, Grady M (1995) P-selectin blockade after fluid percussion injury: behavioral and anatomic sequelae. J Neurotrauma 12:976

    Google Scholar 

  • DeKosky ST, Goss JR, Miller PD, Styren SD, Kochanek PM, Marion D (1994) Upregulation of nerve growth factor following cortical trauma. Exp Neurol 130:173–177

    Article  CAS  PubMed  Google Scholar 

  • DeKosky ST, Styren S, O’Malley M et al (1996) Interleukin-1 receptor antagonist suppresses neurotrophin response in injured rat brain. Ann Neurol 39:123–127

    Article  CAS  PubMed  Google Scholar 

  • Ellis EF, Chao J, Heizer ML (1989) Brain kininogen following experimental brain injury: evidence for a secondary event. J Neurosurg 71:437–442

    Article  CAS  PubMed  Google Scholar 

  • Frei K, Nadal D, Fontana A (1990) Intracerebral synthesis of tumor necrosis factor-alpha and interleukin-6 in infectious meningitis. Ann NY Acad Sci 594:326–335

    Article  CAS  PubMed  Google Scholar 

  • Gallinaro R, Cheadle W, Applegate K et al (1992) The role of the complement system in trauma and infection. Surg Gynecol Obstet 174:435–440

    CAS  PubMed  Google Scholar 

  • Giulian D (1987) Ameboid microglia as effectors of inflammation inthe central nervous system. J Neurosci Res 18:155–171, 132–133

    Article  CAS  PubMed  Google Scholar 

  • Giulian D, Lachman L (1985) Interleukin-1 stimulation of astroglial proliferation after brain injury. Science 228:497–498

    Article  CAS  PubMed  Google Scholar 

  • Giulian D, Robertson C (1990) Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord. Ann Neurol 27:33–42

    Article  CAS  PubMed  Google Scholar 

  • Goss J, Styren S, Miller P et al (1995) Hypothermia attenuates the normal increase in interleukin Iβ RNA and nerve growth factor following traumatic brain injury in the rat. J Neurotrauma 12:159–167

    Article  CAS  PubMed  Google Scholar 

  • Hallenbeck J (1977) Prevention of postischemic impairment of microvascular perfusion. Neurology 27:3–10

    Article  CAS  PubMed  Google Scholar 

  • Hallenbeck JM, Dutka AJ, Tanishima T et al (1986) Polymorphonuclear leukocyte accumulation in regions with low blood flow during the postischemic period. Stroke 17:246–253

    Article  CAS  PubMed  Google Scholar 

  • Hewett S, Corbett J, McDaniel M, Choi D (1993) Interferony and interleukin-Iβ induce nitric oxide formation from primary mouse astrocytes. Neurosci Lett 164:229–232

    Article  CAS  PubMed  Google Scholar 

  • Horner H, Setler P, Fritz L et al (1992) Characterization of leukocyte infiltration in traumatic brain injury in the rat. Soc Neurosci Abstr 18:173

    Google Scholar 

  • Iadecola C, Zhang F, Xu X (1995) Inhibition of nitric oxide synthase ameliorates cerebral ischemic damage, A. J Physiol 268:R286–R292

    CAS  Google Scholar 

  • Kaczorowski SL, Schiding JK, Toth CA, Kochanek PM (1995) Effect of soluble complement receptor-1 on neutrophil accumulation after traumatic brain injury in rats. J Cereb Blood Flow Metab 15:860–864

    Article  CAS  PubMed  Google Scholar 

  • Kochanek P, Hallenbeck J (1992) Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke 23:1367–1379

    Article  CAS  PubMed  Google Scholar 

  • Ledingham J (1908) The influence of temperature on phagocytosis. Proc R Soc Lond 80:188–195

    Article  Google Scholar 

  • Liebermann AP, Pitha PM, Shin HS et al (1989) Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus. Proc Natl Acad Sci USA 86:6348–6352

    Article  Google Scholar 

  • Lindholm D, Heumann R, Hengerer B, Thoenen H (1988) Interleukin-1 increases stability and transcription of mRNA encoding nerve growth factor in cultured rat fibroblasts. J Biol Chem 263:16348–16351

    CAS  PubMed  Google Scholar 

  • Lindsberg PJ, Hallenbeck JM, Feuerstein G (1991) Platelet-activating factor in stroke and brain injury. Ann Neurol 30:117–129

    Article  CAS  PubMed  Google Scholar 

  • Liu T, Clark R, McDonnell P et al (1994) Tumor necrosis factor-alpha expression in ischemic neurons. Stroke 25:1481–1488

    Article  CAS  PubMed  Google Scholar 

  • MacMicking J, Nathan C, Horn G et al (1995) Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 81:641–650

    Article  CAS  PubMed  Google Scholar 

  • Mansfield RT, Schiding JK, Hamilton RL, Kochanek PM (1996) Effects of hypothermia on traumatic brain injury in immature rats. J Cereb Blood Flow Metab (in press)

    Google Scholar 

  • Marion D, Obrist W, Carlier P, Penrod L, Darby J (1993) The use of moderate therapeutic hypothermia for patients with severe head injuries: a preliminary report. J Neurosurg 79:354–362

    Article  CAS  PubMed  Google Scholar 

  • Marion DW, Penrod LE, Kelsey SF, Obrist WD, Kochanek PM, Palmer AM, Wisniewski SR, DeKosky ST (1997) Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med (in press)

    Google Scholar 

  • Marmarou A, Abd-Elfattah F, Van Den Brink W, Campbell J, Kita H, Demetriadou K (1994) A new model of diffuse brain injury in rats. J Neurosurg 80:291–300

    Article  CAS  PubMed  Google Scholar 

  • Matsuo Y, Onodera H, Shiga Y et al (1994) Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat: effects of neutrophil depletion. Stroke 25:1469–1475

    Article  CAS  PubMed  Google Scholar 

  • Megyeri P, Abraham C, Temesvari P et al (1992) Recombinant human tumor necrosis factor a constricts pial arterioles and increases blood-brain barrier permeability in newborn piglets. Neurosci Lett 148:137–140

    Article  CAS  PubMed  Google Scholar 

  • Movat H (1987) Tumor necrosis factor and interleukin-1: Role in acute inflammation and microvascular injury. J Lab Clin Med 110:668–681

    CAS  PubMed  Google Scholar 

  • Mulligan M, Vaporciyan A, Warner R et al (1995) Compartmentalized roles for leukocytic adhesion molecules in lung inflammatory injury. J Immunol 154:1350–1363

    CAS  PubMed  Google Scholar 

  • Ott L, McClain C, Gillespie M, Young B (1994) Cytokines and metabolic dysfunction after severe head injury. J Neurotrauma 11:447–472

    Article  CAS  PubMed  Google Scholar 

  • Palmer A, Marion D, Botscheller M, Redd E (1993) Therapeutic hypothermia is cytoprotective without attenuating traumatic brain injury-induced elevations in interstitial concentrations of aspartate and glutamate. J Neurotrauma 10:363–372

    Article  CAS  PubMed  Google Scholar 

  • Pasinetti G, Johnson S, Rozovsky I et al (1992) Complement ClqB and C4 RNAs response to lesioning in rat brain. Exp Neurol 118

    Google Scholar 

  • Pastor C, Billiar T (1995) Regulation and functions of nitric oxide in the liver in sepsis and inflammation. New Horiz 3:65–72

    CAS  PubMed  Google Scholar 

  • Pfister H, Koedel U, Haberi R et al (1990) Microvascular changes during the early phase of experimental bacterial meningitis. J Cereb Blood Flow Metab 10:914–922

    Article  CAS  PubMed  Google Scholar 

  • Pinto A, Kuluz J, Schleien C (1996) Cerebral production of IL-Iβ in children with traumatic and anoxic brain injury. Crit Care Med 24 Suppl:A135

    Google Scholar 

  • Rebhun J, Botvin-Madorsky J, Glovsky M (1991) Proteins of the complement system and acute phase reactants in sera of patients with spinal cord injury. Ann Allergy 66:335–338

    CAS  PubMed  Google Scholar 

  • Rothwell N, Lawrence C, Loddick S et al (1994) Cytokines and cerebral ischemia. In: Krieglstein J, Oberpichler-Schwenk H (eds) Pharmacology of cerebral ischemia. Wissenschaftliche Verlagsgesellschaft, Stuttgart, pp 419–425

    Google Scholar 

  • Saez-Llorens X, Jafari H, Severien C et al (1991) Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD 18 monoclonal antibodies and dexamethasone in experimental haemophilus meningitis. J Clin Invest 88:2003–2011

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schoettle RJ, Kochanek PM, Magargee MJ, Uhl MW, Nemoto EM (1990) Early polymorphonuclear leukocyte accumulation correlates with the development of posttraumatic cerebral edema in rats. J Neurotrauma 7:207–217

    Article  CAS  PubMed  Google Scholar 

  • Schürer L, Prugner U, Kempski O, Arfors K-E, Baethmann A (1990) Effects of antineutrophil serum (ANS) on posttraumatic brain oedema in rats. Acta Neurochir (Wien) S51:49–51

    Google Scholar 

  • Shohami E, Novikov M (1994) Closed head injury triggers early production of TNFα and IL-6 by brain tissue. J Cereb Blood Flow Metab 14:615–619

    Article  CAS  PubMed  Google Scholar 

  • Soares HD, Hicks RR, Smith D, Mcintosh TK (1995) Inflammatory leukocyte recruitment and diffuse neuronal degeneration are separate pathological processes resulting from traumatic brain injury. J Neurosci 15:8223–8233

    CAS  PubMed  Google Scholar 

  • Spranger M, Lindholm D, Brandtlow C et al (1990) Regulation of nerve growth factor (NGF) synthesis in the rat central nervous system: comparison between the effects of interleukin- 1 and various growth factors in astrocyte cultures and in vivo. Eur J Neurosci 2:69–76

    Article  PubMed  Google Scholar 

  • Stoclet J, Fleming I, Gray G et al (1993) Nitric oxide and endotoxemia. Circulation 87 Suppl 5:V77–V80

    CAS  Google Scholar 

  • Svanes K (1964) Studies in hypothermia. I. The influence of deep hypothermia on the 2 formation of cellular exudate in acute inflammation in mice. Acta Anaesthesiol Scand 8:143–156

    Article  CAS  PubMed  Google Scholar 

  • Svensson M, Bellander M, Aldskogius H, von Holst H (1994) Evidence for activation of the complement cascade and increase of the complement regulator sulfated glycoprotein-2 in the vicinity of a cortical contusion injury in the adult rat. Soc Neurosci Abstr 20/1:421

    Google Scholar 

  • Symons J, Bundick R, Suckling A et al (1987) Cerebrospinal fluid interleukin 1 like activity during chronic relapsing experimental allergic encephalomyelitis. Clin Exp Immunol 68:648–654

    CAS  PubMed Central  PubMed  Google Scholar 

  • Takeshima R, Kirsch J, Koehler R et al (1992) Monoclonal luekocyte antibody does not decrease the injury of transient focal cerebral ischemia in cats. Stroke 23:247–252

    Article  CAS  PubMed  Google Scholar 

  • Tuomanen E, Saukkonen K, Sande S, Cioffe C, Wright S (1989) Reduction of inflammation, tissue damage, and mortality in bacterial meningitis in rabbits treated with monoclonal antibodies against adhesion-promoting receptors of leukocytes. J Exp Med 170:959–968

    Article  CAS  PubMed  Google Scholar 

  • Uhl MW, Biagas KV, Grundl PD et al (1994) Effects of neutropenia on edema, histology, and cerebral blood flow after traumatic brain injury in rats. J Neurotrauma 11:303–315

    Article  CAS  PubMed  Google Scholar 

  • Unterberg A, Baethmann AJ (1984) The kallirein-kinin system as mediator in vasogenic brain edema. J Neurosurg 61:87–96

    Article  CAS  PubMed  Google Scholar 

  • Whalen MJ, Carlos TM, Kochanek PM et al (1996) Hypothermia reduces acute inflammation after traumatic brain injury in rats (Abstr). Pediatr Res (in press)

    Google Scholar 

  • Yakolev AG, Faden AI (1995) Molecular strategies in CNS injury. J Neurotrauma 12:767–778

    Article  Google Scholar 

  • Yamasaki Y, Matsuo Y, Matsuura N, Onodera H, Itoyama Y, Kogure K (1995) Transient increase of cytokine-induced neutrophil chemoattractant, a member of the interleukin-8 family, in ischemic brain areas after focal ischemia in rats. Stroke 26:318–323

    Article  CAS  PubMed  Google Scholar 

  • Zhang R, Chopp M, Li Y et al (1994) Anti-ICAM-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat. Neurology 44:1747–1751

    Article  CAS  PubMed  Google Scholar 

Download references

Authors
  1. P. M. Kochanek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. T. DeKosky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Carlos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. S. B. Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Whalen
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Ludwig-Boltzmann-Institut für experimentelle und klinische Traumatologie, Donaueschingenstraße 13, 1200, Wien, Austria

    Günther Schlag  & Heinz Redl  & 

  2. Investigational Intensive Care Unit, Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, 77555-0833, USA

    Daniel Traber Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Kochanek, P.M., DeKosky, S.T., Carlos, T., Clark, R.S.B., Whalen, M. (1997). Inflammatory Process in the Pathobiology of Secondary Damage After Traumatic Brain Injury. In: Schlag, G., Redl, H., Traber, D. (eds) Shock, Sepsis, and Organ Failure. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60698-4_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-60698-4_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64513-6

  • Online ISBN: 978-3-642-60698-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation