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

  • P. M. Kochanek
  • S. T. DeKosky
  • T. Carlos
  • R. S. B. Clark
  • M. Whalen
Conference paper

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.

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References

  1. Albina J, Cui S, Mateo R, Reichner J (1993) Nitric oxide-mediated apoptosis in murine peritoneal macrophages. J Immunol 150:5080–5085PubMedGoogle Scholar
  2. Becker P, Zieger S, Rother U et al (1987) Complement activation following severe head injury. Anaesthesist 36:301–305PubMedGoogle Scholar
  3. 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 15:547–551PubMedCrossRefGoogle Scholar
  4. 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 48:565–569Google Scholar
  5. 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 14:529PubMedCrossRefGoogle Scholar
  6. 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 12:458Google Scholar
  7. 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 25:869–876PubMedCrossRefGoogle Scholar
  8. 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 11:499–506PubMedCrossRefGoogle Scholar
  9. 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 37:43AGoogle Scholar
  10. 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 13:333–341PubMedGoogle Scholar
  11. 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 16:253–261PubMedCrossRefGoogle Scholar
  12. 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 39:784–790PubMedCrossRefGoogle Scholar
  13. 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 24:1243–1251PubMedCrossRefGoogle Scholar
  14. 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 11:114–121PubMedCrossRefGoogle Scholar
  15. Cody R, Maris D, Seckin H, Sharar S, Grady M (1995) P-selectin blockade after fluid percussion injury: behavioral and anatomic sequelae. J Neurotrauma 12:976Google Scholar
  16. DeKosky ST, Goss JR, Miller PD, Styren SD, Kochanek PM, Marion D (1994) Upregulation of nerve growth factor following cortical trauma. Exp Neurol 130:173–177PubMedCrossRefGoogle Scholar
  17. DeKosky ST, Styren S, O’Malley M et al (1996) Interleukin-1 receptor antagonist suppresses neurotrophin response in injured rat brain. Ann Neurol 39:123–127PubMedCrossRefGoogle Scholar
  18. Ellis EF, Chao J, Heizer ML (1989) Brain kininogen following experimental brain injury: evidence for a secondary event. J Neurosurg 71:437–442PubMedCrossRefGoogle Scholar
  19. Frei K, Nadal D, Fontana A (1990) Intracerebral synthesis of tumor necrosis factor-alpha and interleukin-6 in infectious meningitis. Ann NY Acad Sci 594:326–335PubMedCrossRefGoogle Scholar
  20. Gallinaro R, Cheadle W, Applegate K et al (1992) The role of the complement system in trauma and infection. Surg Gynecol Obstet 174:435–440PubMedGoogle Scholar
  21. Giulian D (1987) Ameboid microglia as effectors of inflammation inthe central nervous system. J Neurosci Res 18:155–171, 132–133PubMedCrossRefGoogle Scholar
  22. Giulian D, Lachman L (1985) Interleukin-1 stimulation of astroglial proliferation after brain injury. Science 228:497–498PubMedCrossRefGoogle Scholar
  23. Giulian D, Robertson C (1990) Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord. Ann Neurol 27:33–42PubMedCrossRefGoogle Scholar
  24. 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 12:159–167PubMedCrossRefGoogle Scholar
  25. Hallenbeck J (1977) Prevention of postischemic impairment of microvascular perfusion. Neurology 27:3–10PubMedCrossRefGoogle Scholar
  26. Hallenbeck JM, Dutka AJ, Tanishima T et al (1986) Polymorphonuclear leukocyte accumulation in regions with low blood flow during the postischemic period. Stroke 17:246–253PubMedCrossRefGoogle Scholar
  27. Hewett S, Corbett J, McDaniel M, Choi D (1993) Interferony and interleukin-Iβ induce nitric oxide formation from primary mouse astrocytes. Neurosci Lett 164:229–232PubMedCrossRefGoogle Scholar
  28. Horner H, Setler P, Fritz L et al (1992) Characterization of leukocyte infiltration in traumatic brain injury in the rat. Soc Neurosci Abstr 18:173Google Scholar
  29. Iadecola C, Zhang F, Xu X (1995) Inhibition of nitric oxide synthase ameliorates cerebral ischemic damage, A. J Physiol 268:R286–R292Google Scholar
  30. 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 15:860–864PubMedCrossRefGoogle Scholar
  31. Kochanek P, Hallenbeck J (1992) Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke 23:1367–1379PubMedCrossRefGoogle Scholar
  32. Ledingham J (1908) The influence of temperature on phagocytosis. Proc R Soc Lond 80:188–195CrossRefGoogle Scholar
  33. 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 86:6348–6352CrossRefGoogle Scholar
  34. 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 263:16348–16351PubMedGoogle Scholar
  35. Lindsberg PJ, Hallenbeck JM, Feuerstein G (1991) Platelet-activating factor in stroke and brain injury. Ann Neurol 30:117–129PubMedCrossRefGoogle Scholar
  36. Liu T, Clark R, McDonnell P et al (1994) Tumor necrosis factor-alpha expression in ischemic neurons. Stroke 25:1481–1488PubMedCrossRefGoogle Scholar
  37. 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 81:641–650PubMedCrossRefGoogle Scholar
  38. 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
  39. 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 79:354–362PubMedCrossRefGoogle Scholar
  40. 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
  41. 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 80:291–300PubMedCrossRefGoogle Scholar
  42. 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 25:1469–1475PubMedCrossRefGoogle Scholar
  43. 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 148:137–140PubMedCrossRefGoogle Scholar
  44. Movat H (1987) Tumor necrosis factor and interleukin-1: Role in acute inflammation and microvascular injury. J Lab Clin Med 110:668–681PubMedGoogle Scholar
  45. Mulligan M, Vaporciyan A, Warner R et al (1995) Compartmentalized roles for leukocytic adhesion molecules in lung inflammatory injury. J Immunol 154:1350–1363PubMedGoogle Scholar
  46. Ott L, McClain C, Gillespie M, Young B (1994) Cytokines and metabolic dysfunction after severe head injury. J Neurotrauma 11:447–472PubMedCrossRefGoogle Scholar
  47. 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 10:363–372PubMedCrossRefGoogle Scholar
  48. Pasinetti G, Johnson S, Rozovsky I et al (1992) Complement ClqB and C4 RNAs response to lesioning in rat brain. Exp Neurol 118Google Scholar
  49. Pastor C, Billiar T (1995) Regulation and functions of nitric oxide in the liver in sepsis and inflammation. New Horiz 3:65–72PubMedGoogle Scholar
  50. Pfister H, Koedel U, Haberi R et al (1990) Microvascular changes during the early phase of experimental bacterial meningitis. J Cereb Blood Flow Metab 10:914–922PubMedCrossRefGoogle Scholar
  51. 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:A135Google Scholar
  52. 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 66:335–338PubMedGoogle Scholar
  53. 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 419–425Google Scholar
  54. 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 88:2003–2011PubMedCentralPubMedCrossRefGoogle Scholar
  55. 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 7:207–217PubMedCrossRefGoogle Scholar
  56. 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) S51:49–51Google Scholar
  57. Shohami E, Novikov M (1994) Closed head injury triggers early production of TNFα and IL-6 by brain tissue. J Cereb Blood Flow Metab 14:615–619PubMedCrossRefGoogle Scholar
  58. 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 15:8223–8233PubMedGoogle Scholar
  59. 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 2:69–76PubMedCrossRefGoogle Scholar
  60. Stoclet J, Fleming I, Gray G et al (1993) Nitric oxide and endotoxemia. Circulation 87 Suppl 5:V77–V80Google Scholar
  61. 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 8:143–156PubMedCrossRefGoogle Scholar
  62. 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 20/1:421Google Scholar
  63. Symons J, Bundick R, Suckling A et al (1987) Cerebrospinal fluid interleukin 1 like activity during chronic relapsing experimental allergic encephalomyelitis. Clin Exp Immunol 68:648–654PubMedCentralPubMedGoogle Scholar
  64. 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 23:247–252PubMedCrossRefGoogle Scholar
  65. 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 170:959–968PubMedCrossRefGoogle Scholar
  66. 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 11:303–315PubMedCrossRefGoogle Scholar
  67. Unterberg A, Baethmann AJ (1984) The kallirein-kinin system as mediator in vasogenic brain edema. J Neurosurg 61:87–96PubMedCrossRefGoogle Scholar
  68. 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
  69. Yakolev AG, Faden AI (1995) Molecular strategies in CNS injury. J Neurotrauma 12:767–778CrossRefGoogle Scholar
  70. 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 26:318–323PubMedCrossRefGoogle Scholar
  71. 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 44:1747–1751PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • P. M. Kochanek
  • S. T. DeKosky
  • T. Carlos
  • R. S. B. Clark
  • M. Whalen

There are no affiliations available

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