Summary
The inflammatory reaction following experimental brain contusion was studied by immunohistochemistry in 22 rats during the first 16 days after trauma. An inflammatory mononuclear cell response was evident on day 2, with a maximum on days 5–6 and signs remained still 16 days after the trauma. The time course of the cellular infiltration adjacent to the lesion correlated with blood brain barrier dysfunction in the contralateral side of the traumatized hemisphere. The cellular infiltrate comprised NK cells, T-helper cells and T-cytotoxic/suppressor cells as well as monocytes/macrophages. Most of the macrophages appeared to be activated by T-cells. Surprisingly, polymorphonuclear cells appeared less engaged than mononuclear cells in the inflammation.
The demonstration of immunocompetent cells and the induction of MHC-1 and MHC-II antigen provides a substrate for inflammatory reactions similar to those that cause neurological damage in inflammatory diseases such as viral infections, multiple sclerosis and experimental allergic encephalitis. Our observations indicate that the role of the inflammatory reactions may have a role, hitherto neglected, in the pathogenesis of secondary traumatic brain injury.
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References
Andersson PB, Perry VH, Gordon S (1991) The CNS acute inflammatory response to excitotoxic cell death. Immunol Lett 30: 177–182
Barbé E, Damoiseaux JGMC, Döpp EA,et al (1990) Characterization and expression on resident rat macrophages recognized by monoclonal antibody ED 2. Immunobiology 182: 88–89
Barclay AN (1981) The localisation of populations of lymphocytes defined by monoclonal antibodies in rat lymphoid tissues. Immunology 42: 593–600
Blight AR (1985) Delayed demyelination and macrophage invasion: a candidate for secondary cell damage in spinal cord injury. Cent Nerv Syst Trauma 2: 299–315
Blight AR (1992) Macrophages and inflammatory damage in spinal cord injury. J Neurotrauma 9 [Suppl 1]: 83–91
Brideau RJ, Carter RB, Mc Master WR,et al (1980) Two subsets of T lymphocytes defined with monoclonal antibodies. Eur J Immunol 10: 609–615
van den Brink MRM, Hunt LE, Hiserodt JC (1990) In vivo treatment with monoclonal antibody 3.2.3 selectively eliminates natural killer cells in rats. J Exp Med 171: 197–210
Brown WRA, Barclay AN, Sunderland CA,et al (1981) Identification of a glycophorin-like molecule at the cell surface of rat lymphocytes. Nature 289: 456–460
Bullock R, Maxwell WL, Graham DI,et al (1991) Glial swelling following human cerebral contusion: an ultrastructural study. J Neurology Neurosurg Psychiatry 54: 427–434
Bullock R, Teasdale GM, Wyper D,et al (1989) Tomographic mapping of CBF, CBV and BBB changes after focal haed injury using SPECT: mechanisms for late deterioration. In: Hoff J (ed) Proceedings of the VIIth International Symposium of Intracranial Pressure and Brain injury. Springer, Berlin Heidelberg New York Toyko, pp 637–639
Cervos-Navarro J, Lafuente JV (1991) Traumatic brain injuries: structural changes. J Neurol Sci 103: 3–14
Chambers WH, Vujanovic AB, Deleo AB,et al (1989) Monoclonal antibody to a triggering structure expressed on rat natural killer cells and adherent lymphokine activated killer cells. J Exp Med 169: 1373
Cuzner ML, Hayes GM, Newcombe J,et al (1988) The nature of inflammatory components during demyelination in multiple sclerosis. J Neuroimmunol 20: 203–209
Dallman MJ, Mason DW, Webb M (1982) The roles of host and donor cells in the rejection of skin allografts by T cell-deprived rats injected with syngeneic T cells. Eur J Immunol 12: 511–518
Dallman MJ, Thomas ML, Green JR (1984) MRC OX-19: a monoclonal antibody that labels rat T lymphocytes and augments in vitro proliferative responses. Eur J Immunol 14: 260–267
Damoiseaux JGMC, Döpp EA, Beelen RHJ,et al (1989) Rat bone marrow and monocyte cultures: influence of culture time and lymphokines on the expression of macrophage differentiation antigens. J Leukocyte Biology 46: 246–253
Dijkstra CD, Döpp EA, Joling P,et al (1985) The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED 1, ED 2 and ED 3. Immunology 54: 589–599
Dijkstra CD, Döpp EA, Vogels IMC,et al (1987) Macrophages and dendritic cells in antigen induced arthritis: an immunohistochemical study using cryostat sections of the whole knee joint of rat. Scand J Immunol 26: 513–523
Faden AI, Demediuk P, Panter SS,et al (1989) The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244: 798–800
Feeney DM, Boyeson MG, Linn RT,et al (1981) Responses to cortical injury: methodology and local effects of contusions in the rat. Brain Res 211: 67–77
Fukumoto T, Mc Master WR, Williams AF (1982) Mouse monoclonal antibodies against rat major histocompatibility antigens. Two I a antigens and expression of I a and class I antigens in rat thymus. Eur J Immunol 12: 237–243
Giulian D (1987) Ameboid microglia as effectors of inflammation in the central nervous system. J Neurosci Res 18: 155–171
Giulian D, Chen J, Ingeman JE,et al (1989) The role of mononuclear phagocytes in wound healing after traumatic injury to adult mammalian brain. J Neurosci 9: 4416–4429
Hayes GM, Woodroofe MN, Cuzner ML (1988) Characterisation of microglia isolated from adult human and rat brain. J Neuroimmunol 19: 177–189
Hickey WF, Kimura H (1987) Graft-vs-host disease elicits expression of class I and class II histocompatibility antigens and the presence of scattered T lymphocytes in rat central nervous system. Proc Natl Acad Sci USA 84: 2082–2086
Hickey WH, Ueno K, Hiserodt JC,et al (1992) Exogenously-induced, natural killer cell-mediated neuronal killing: a novel pathogenetic mechanism. J Exp Med 176: 811–817
Jie Z, Ivarsson B, Collins P (1986) Monoclonal antibodies to GFAP epitopes available in formaldehyde fixed tissue. Acta Path Microbiol Immunol Scand Sect A 94: 53–361
Katayama Yet al (1990) Oedema fluid formation within contused brain tissue as a cause of medically uncontrollable elevation of intracranial pressure: the role of surgical therapy. Acta Neurochir (Wien) [Suppl] 54: 308–310
Kaur C, Ling EA, Wong WC (1987) Origin and fate of neural macrophages in a stab wound of the brain of the young rat. J Anat 154: 215–227
Kearney JF, Rabruch A, Liesegang B,et al (1979) A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol 123: 1548–1550
Koenig S, Gendelman HE, Orenstein JM,et al (1986) Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233: 1089–1093
Kwo S, Young W, Decrescito V (1989) Spinal cord sodium, pottasium, calcium and water concentration changes in rats after graded contusion injury. J Neurotrauma 6: 13–24
Lampson LA, Hickey WF (1986) Monoclonal antibody analysis of MHC expression in human brain biopsies: tissue ranging from “histologically normal” to that showing different levels of glial tumour involvement. J Immunol 136: 4045–4062
Lampson LA (1987) Molecular bases of the immune response to neural antigens. Trends Neurosci 10: 211–216
Liu HM, Sturner WQ (1988) Extravasation of plasma proteins in brain trauma. Forensic Sci Int 38: 285–295
Ljunggren HG, Yamasaki T, Collins P,et al (1988) Selective acceptance of MHC class I-deficient tumour grafts in the brain. J Exp Med 167: 730–735
Luz C, Kress Y, Factor J,et al (1990) Mechanisms of oedema formation in experimental autoimmune encephalomyelitis. Am J Pathol 137: 1033–1045
Main EK, Monos DS, Lampson LA (1988) IFN-treated neuroblastoma cell lines remain resistant to T cell-mediated allokilling, and susceptible to non-MHC restricted cytotoxictiy. J Immunol 141: 2943–2950
Mc Master WR, Williams AF (1979) Identification of I a glycoproteins in rat thymus and purification from rat spleen. Eur J Immunol 9: 426–433
Bilsson B, Nordström CH (1977) Experimental head injury in the rat, Pt 3. Cerebral blood flow and oxygen consumption after concussive impact acceleration. J Neurosurg 47: 262–273
Nilsson P, Hillered L, Pontén U,et al (1990) Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J Cereb Blood Flow Metabol 10: 631–637
Olsson T, Maehlen J, Löve A,et al (1987) Induction of class I and class II transplantation antigens in rat brain during fatal and non-fatal measles virus infection. J Neuroimmunol 16: 215–224
Ortaldo J, Sharrow SO, Timonen T,et al (1981) Determination of surface antigens on highly purified human NK-cells by flow cytometry with monoclonal antibodies. J Immunol 127: 2401–2409
Perry VH, Gordon S (1987) Modulation of CD 4 antigen on macrophages and microglia in rat brain. J Exp Med 10: 1138–1143
Persson L (1976) Cellular reactions to small cerebral stab wounds in the rat frontal lobe. Virchows Arch B Cell Path 22: 21–37
Polman CH, Dijkstra CD, Sminia T,et al (1986) Immunohistological analysis of macrophages in the central nervous system of Lewis rats with acute experimental allergic encephalomyelitis. J Neuroimmunol 11: 215–222
Povlishock JT, Becker DP, Sullivan HG,et al (1978) Vascular permeability alterations to horse radish peroxidase in experimental brain injury. Brain Res 153: 223–239
Rogers J, Luber-Narod J (1988) Immune actions in the nervous system: a brief review with special emphasis on Alzheimers disease. Drug Dev Res 15: 227–235
Sethna MP, Lampson LA (1991) Immune modulation within the brain: recruitment of inflammatory cells and increased major histocompatibility antigen expression following intracerebral injection of interferon-gamma. J Neuroimmunol 34: 121–132
Sminia T, De Groot CJA, Dijkstra CD,et al (1987) Macrophages in the central nervous system of the rat. Immunobiology 174: 43–50
Streit WJ, Graeber MB, Kreutzberg GW (1988) Functional plasticity of microglia: a review. GLIA 1: 301–307
Todd NV, Graham DI (1990) Blood-brain-barrier damage in traumatic brain contusions. Acta Neurochir (Wien) [Suppl] 51: 296–299
Trincieri G, Matsumoto-Kobayashi M, Clark SV,et al (1984) Response of resting human peripheral blood natural killer cells by interleukin-2. J Exp Med 160: 1147–1169
Turner WJD, Chatten J, Lampson LA (1990) Human neuroblastoma cell growth in xenogeneic hosts: comparison of T celldeficient and NK-deficient hosts, and subcutaneous or intravenous injection routes. J Neurooncol 8: 121–132
Unterberg A, Kiening K, Schmiedele P,et al (1993) Long-term observations of intracranial pressure after severe head injury. The phenomenon of secondary rise of intracranial pressure. Neurosurgery 32: 17–24
Wekerle H, Linington C, Lassman H,et al (1986) Cellular immune reactivity within the CNS. Trends Neurosci 9: 271–277
Wekerle H, Sun D, Ortpeza-Wekerle,et al (1987) Immune reactivity in the nervous system: modulation of T-lymphocyte activation by glial cells. J Exp Biol 132: 43–57
White RAH, Mason DW, William AF,et al (1978) T lymphocyte heterogeneity in the rat: separation of functional subpopulations using a monoclonal antibody. J Exp Med 901: 664
Williams AF, Galfrè G, Milstein C (1977) Analysis of cell surfaces by xenogeneic myeloma-hybrid antibodies. Differentiation antigens on rat lymphocytes. Cell 12: 633–673
Wilmes F, Hossman KA (1979) A specific immunofluorescence technique for the demonstration of vasogenic brain edema in paraffin embedded material. Acta Neuropathol 45: 47–51
Woodroofe MN, Sarna GS, Wadhwa M,et al (1991) Detection of interleukin-1 and interleukin-6 in adult rat brain, following mechanical injury, by in vivo microdialysis: evidence of a role of microglia in cytokine production. J Neuroimmunol 33: 227–236
Woolett GR, Barclay AN, Puklavec M,et al (1985) Molecular and antigenic heterogeneity of the rat leukocyte common antigen from thymocytes and T and B lymphocytes. Eur J Immunol 15: 168–173
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This study was supported by 1987 Års fond för Strokeforskning and Swedish Society of Medicine.
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Holmin, S., Mathiesen, T., Shetye, J. et al. Intracerebral inflammatory response to experimental brain contusion. Acta neurochir 132, 110–119 (1995). https://doi.org/10.1007/BF01404857
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DOI: https://doi.org/10.1007/BF01404857