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Detrimental and Beneficial Effects of Injury-Induced Inflammation and Cytokine Expression in the Nervous System

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Molecular and Cellular Biology of Neuroprotection in the CNS

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 513))

Abstract

Lesions in the nervous system induce rapid activation of glial cells and under certain conditions additional recruitment of granulocytes, T-cells and monocytes/ macrophages from the blood stream triggered by upregulation of cell adhesion molecules, chemokines and cytokines. Hematogenous cell infiltration is not restricted to infectious or autoimmune disorders of the nervous system, but also occurs in response to cerebral ischemia and traumatic lesions. Neuroinflammation can cause neuronal damage, but also confers neuroprotection.

Granulocytes occlude vessels during reperfusion after transient focal ischemia, while the functional role of T-cells and macrophages in stroke development awaits further clarification. After focal cerebral ischemia neurotoxic mediators released by microglia such as the inducible nitric oxide synthase (leading to NO synthesis) and the cytokines interleukin-1ß (IL-ß) and tumor necrosis factor-a (TNF-α) are upregulated prior to cellular inflammation in the evolving lesion and functionally contribute to secondary infarct growth as revealed by numerous pharmacological experiments and by use of transgenic animals. On the other hand, cytokine induction remote from ischemic lesions involves NMDA-mediated signalling pathways and confers neuroprotection. After nerve injury T cells can rescue CNS neurons. In the peripheral nervous system neuroinflammation is a prerequisite for successful regeneration that is impeded in the CNS. In conclusion, there is increasing evidence that neuroinflammation represents a double edged sword. The opposing neurotoxic and neuroprotective properties of neuroinflammation during CNS injury provide a rich and currently unexplored set of research problems.

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References

  1. Ridet JL, Malhotra SK, Privat A, Gage FH. Reactive astrocytes: CeIJular and molecular cues to biological function. Trends Neurosci 1997; 20:570–577.

    CAS  PubMed  Google Scholar 

  2. Constam DB, Philipp J, Malipiero UV, Ten Dijke P, Schachner M, Fontana A. Differential expression of transforming growth factor-beta 1, beta 2, and beta 3 by glioblastoma cells, astrocytes, and microglia. J Immunol 1992; 148:1404–1410.

    CAS  PubMed  Google Scholar 

  3. Jander S, Pohl J, D«Urso D, Gillen C, Stoll G. Time course and cellular localisation of interleukin-10 mRNA and protein expression in autoimmune inflammation of the rat central nervous system. Am J Pathol 1998; 152:975–982.

    CAS  PubMed  Google Scholar 

  4. Men ndez Iglesias B, Cerase J, Ceracchini C, Levi G, Aloisi F. Analysis of B7–1 and B7–2 costimulatory ligands in cultured mouse microglia: Upregulation by interferon-gamma and lipopolysaccharide and downregulation by interleukin-l0, prostaglandin E2 and cAMPelevating agents. J Neuroimmunol 1997; 72:83–93.

    Google Scholar 

  5. Letterio JJ, Roberts AB. Regulation of immune responses by TGF-ß. Annu Rev Immunol 1998; 16:137–161

    CAS  PubMed  Google Scholar 

  6. Kreutzberg GW. Microglia: A sensor for pathological events in the CNS. Trends Neurosci 1996; 19:312–318.

    CAS  PubMed  Google Scholar 

  7. Stoll G, Dander S. The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 1999; 58:233–247.

    CAS  PubMed  Google Scholar 

  8. Flans NA, Densmore TL, Molleston MC, Hickey WF. Characterization of microglia and macrophages in the central nervous system of rats: Definition of the differential expression of molecules using standard and novel monoclonal antibodies in normal CNS and in four models of parenchymal reaction. Glia 1993; 7:34–40.

    Google Scholar 

  9. Piani D, Frei K, Do KQ, Cuenod M, Fontana A. Murine brain macrophages induce NMDA receptor mediated neurotoxicity in vitro by secreting glutamate. Neurosci Lett 1991; 133:159–162.

    CAS  PubMed  Google Scholar 

  10. Chao CC, Hu S, Molitor TW, Shaskan EG, Peterson PK. Activated microglia mediate neuronal cell injury via a nitric oxide mechanism. J Immunol 1992; 149:2736–2741.

    CAS  PubMed  Google Scholar 

  11. Banati RB, Gehrmann J,Schubert P, Kreutzberg GW. Cytotoxicity of microglia. Glia 1993; 7:111–118.

    CAS  PubMed  Google Scholar 

  12. Giulian D, Corpuz M, Chapman S, Mansouri M, Robertson C. Reactive mononuclear phagocytes release neurotoxins after ischemic and traumatic injury to the central nervous system. J Neurosci Res 1993; 36:681–693.

    CAS  PubMed  Google Scholar 

  13. Zielasek J, Hartung HP. Molecular mechanisms of microglial activation. Adv Neuroimmunol 1996; 6:191–222.

    CAS  PubMed  Google Scholar 

  14. Flavin MP, Coughlin K, Ho LT. Soluble macrophage factors trigger apoptosis in cultured hippocampal neurons. Neurosci 1997; 80:437–448.

    CAS  Google Scholar 

  15. Minghetti L, Levi G. Microglia as effector cells in brain damage and repair: Focus on prostanoids and nitric oxide. Prog Neurobiol 1998; 54:99–125.

    CAS  PubMed  Google Scholar 

  16. Ellison JA, Velier JJ, Spear P, Jonak ZL, Wang X, Barone FC, Feuerstein GZ. Osteopontin and its integrin receptor alpha(v)beta3 are upregulated during formation of the glial scar after focal stroke. Stroke 1998; 29:1698–1706.

    CAS  PubMed  Google Scholar 

  17. Elkabes S, DiCicco-Bloom EM, Black IB. Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. J Neurosci 1996; 16:2508–2521.

    CAS  PubMed  Google Scholar 

  18. Heese K, Hock C, Otten U. Inflammatory signals induce neurotrophin expression in human microglial cells. J Neurochem 1998; 70:699–707.

    CAS  PubMed  Google Scholar 

  19. Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell 1994; 76:301–314.

    CAS  PubMed  Google Scholar 

  20. McAuley MA. Rodent models of focal ischemia. Cerebrovasc Brain Metabol Rev 1995; 7:153–180.

    CAS  Google Scholar 

  21. Stoll G, Jander S, Schroeter M. Inflammation and glial responses in ischemic brain lesions. Prog Neurobiol 1998; 56:149–161.

    CAS  PubMed  Google Scholar 

  22. Memezawa H, Smith ML, Siesj BK. Penumbral tissues salvaged by reperfusion following middle cerebral artery occlusion in rats. Stroke 1992; 23:552–559.

    CAS  PubMed  Google Scholar 

  23. Zhang ZG, Chopp M, Powers C. Temporal profile of microglial response following transient (2h) middle cerebral artery occlusion. Brain Res 1997; 744:189–198.

    CAS  PubMed  Google Scholar 

  24. Watson BD, Dietrich D, Busto R, Wachtel MS, Ginsberg MD. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol 1985; 17:497–504.

    CAS  PubMed  Google Scholar 

  25. Schroeter M, Franke C, Stoll G, Hoehn M. Dynamic changes of MRI abnormalities in relation to inflammation and glial responses after photothrombotic cerebral infarction in the rat brain. Acta Neuropathol 2001; 101:114–122.

    CAS  PubMed  Google Scholar 

  26. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: An integrated view. Trends Neurosci 1999; 22:391–397.

    CAS  PubMed  Google Scholar 

  27. Bredesen DE. Neural apoptosis. Ann Neurol 1995; 38:839–851.

    CAS  PubMed  Google Scholar 

  28. Li Y, Sharov VG°, Jiang N, Zalonga C, Sabbah HN, Chopp M. Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat. Am J Pathol 1995; 146:1045–1051.

    CAS  PubMed  Google Scholar 

  29. Braun JS, Jander S, Schroeter M, Witte OW, Stoll G. Spatiotemporal relationship of apoptotic cell death to lymphomonocytic infiltration in photochemically induced focal ischemia of the rat cerebral cortex. Acta Neuropath. 1996; 92:255–263.

    CAS  PubMed  Google Scholar 

  30. Isenmann S, Stoll G, Schroeter M, Krajewski S, Reed JC, B hr M Differential regulation of Bax, bcl-2, and bel-x proteins in focal cortical ischemia in the rat. Brain Pathol 1998; 8:49–63.

    CAS  PubMed  Google Scholar 

  31. Iadecola C, Zhang F, Casey R, Nagayama M, Ross ME. Delayed reduction of ischemic brain injury and neurological deficits in mice lacking the inducible nitric oxide synthase gene. J Neurosci 1997; 17:9157–9164.

    CAS  PubMed  Google Scholar 

  32. Iadecola C, Salkowski CA, Zhang F, Aber T, Nagayama M, Vogel SN, Ross ME. The transcription factor interferon regulatory factor 1 is expressed after cerebral ischemia and contributed to ischemic brain injury. J Exp Med 1999; 189:719–727.

    CAS  PubMed  Google Scholar 

  33. Bhat RV, RiRocco R, Marcy VR, Flood DG, Zhu Y, Dobrzanski P, Siman R, Scott R, Contreras PC, Miller M. Increased expression of ILI-43 converting enzyme in hippocampus after ischemia: Selective localization in microglia. J Neurosci 1996; 16:4146–4154.

    CAS  PubMed  Google Scholar 

  34. Iadecola C. Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci 1997; 20:132–139.

    CAS  PubMed  Google Scholar 

  35. Bidmon HJ, Wu J, Buchkremer-Raztmann I, Mayer B, Witte OW, Zilles K. Transient changes in the presence of nitric oxide synthases and nitrotyrosine immunoreactivity after focal cortical lesions. Neuroscience 1998; 82:377–395.

    CAS  PubMed  Google Scholar 

  36. Kochanek PM, Hallenbeck JM. Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke 1992; 23:1367–1379.

    CAS  PubMed  Google Scholar 

  37. Garcia JH, Liu KF, Yoshida Y, Lian J, Chen S, del Zoppo G. Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat). Am J Pathol 1994; 144:188–199.

    CAS  PubMed  Google Scholar 

  38. Clark WM, Lauten JD, Lessov N, Woodward W, Coull BM. Time course of ICAM-1 expression and leukocyte subset infiltration in rat forebrain ischemia. Mol Chem Neuropathol 1995; 26:213–230.

    CAS  PubMed  Google Scholar 

  39. Yamasaki Y, Matsuo Y, Matsuura N, Onodera H, Itoyama Y, Kogure K. Transient increase of cytokine-induced neutrophil chemoattractant, a member of the interleukin-8 family, in ischemic brain areas after focal ischemia in rats. Stroke 1995; 26:318–322.

    CAS  PubMed  Google Scholar 

  40. Okada Y, Copeland BR, Mori E, Tung MM, Thomas WS, del Zoppo GJ. P-selektin and intercellular adhesion molecule-1 expression after focal brain ischemia and reperfusion. Stroke 1994; 25:202–211.

    CAS  PubMed  Google Scholar 

  41. Jander S, Kraemer M, Schroeter M, Witte OW, Stoll G. Lymphocytic infiltration and expression of intercellular adhesion molecule-1 in photochemically induced ischemia of the rat cortex. J Cereb Blood Flow Metabol 1995; 15:42–51.

    CAS  Google Scholar 

  42. Zhang RL,Chopp M, Zalonga C, Jiang N, Gautam SC, Tang WX et al. The temporal profiles of ICAM-1 protein and mRNA expression after transient MCA occlusion in the rat. Brain Res 1995; 682:182–188.

    CAS  PubMed  Google Scholar 

  43. Linsberg PJ, Carpen O, Paetau A, Karjalainen-Linsberg ML, Kaste M. Endothelial ICAM-1 expression associated with inflammatory cell response in human ischemic stroke.Circulation 1996; 94:939–945.

    Google Scholar 

  44. Wang X, Yue TL, Barone FC, Feuerstein GZ. Demonstration of increased endothelial-leukocyte adhesion molecule-1 mRNA expression in rat ischemic cortex. Stroke 1995; 26:16651669

    Google Scholar 

  45. Jander S, Pohl J, Gillen C, Schroeter M, Stoll G. Vascular cell adhesion molecule-1 mRNA is expressed in immune-mediated and ischemic injury of the rat nervous system. J Neuroimmunol 1996; 70:75–80.

    CAS  PubMed  Google Scholar 

  46. Chopp M, Li Y, Jiang N, Zhang RL, Prostak J. Antibodies against adhesion molecules reduce apoptosis after middle cerebral artery occlusion in rat brain. J Cereb Blood Flow Metabol 1996; 16:578–584.

    CAS  Google Scholar 

  47. Jiang N, Moyle M, Soule HR, Rote WE, Chopp M. Neutrophile inhibitory factor is neuroprotective after focal ischemia in rats. Ann Neurol 1995; 38:935–942.

    CAS  PubMed  Google Scholar 

  48. Connolly ES, Winfree CJ, Springer TA, Naka Y, Yan SD, Stern DM, Solomon RA, Gutlererez-Ramos JC, Pinski DJ. Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion: role of neutrophil adhesion in the pathogenesis of stroke. J Clin Invest 1996; 97:209–216.

    CAS  PubMed  Google Scholar 

  49. Soriano SG, Lipton SA, Wang YF, Xiao M, Springer TA, Gutierrez-Ramos JC, Hickey PR. Intercellular adhesion molecule-l-deficient mice are less susceptible to cerebral ischemiareperfusion injury. Ann.Neurol 1996; 39:618–624.

    CAS  PubMed  Google Scholar 

  50. Zhang RL, Chopp M, Li Y, Zaloga C, Jiang N, Jones ML et al. Anti-ICAM-1 antibody reduces ischemic cell damage after transient but not permanent MCA occlusion in the Wistar rat. Stroke 1995; 26:1438–1443.

    CAS  PubMed  Google Scholar 

  51. Garcia JH, Liu KR, Bree MP. Effects of CDllb/18 monoclonal antibody on rats with permanent cerebral artery occlusion. Am J Pathol 1996; 148:241–248.

    CAS  PubMed  Google Scholar 

  52. Schroeter M, Jander S, Witte OW, Stoll G. Local immune responses in the rat cerebral cortex after middle cerebral artery occlusion. J Neuroimmunol 1994; 55: 195–203.

    CAS  PubMed  Google Scholar 

  53. Wekerle H. Experimental autoimmune encephalomyelitis as a model of immune-mediated CNS disease. Curr Opin Neurobiol 1993; 3: 779–784.

    CAS  PubMed  Google Scholar 

  54. Garcia JH, Liu KF, Yoshida Y, Lian J, Chen S, del Zoppo GJ. Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat). Am J Pathol 1994;144:188–199.

    CAS  PubMed  Google Scholar 

  55. Rupalla K, Allegrini PR, Sauer D, Wiesner C. Time course of microglia activation and apoptosis in various brain regions after permanent focal cerebral ischemia in mice. Acta Neuropath 1998; 96:172–178.

    CAS  PubMed  Google Scholar 

  56. Clark RK, Lee EV, Fish CJ, White RF, Price WJ, Jonak ZL et al. Development of tissue damage, inflammation and resolution following stroke: An immunohistochemical and quantitative planimetric study. Brain Res Bull 1993; 31:565–572.

    CAS  PubMed  Google Scholar 

  57. Van Roojien N. The liposome-mediated macrophage suicide« technique. J Immunol Meth 1989; 124:1–6.

    Google Scholar 

  58. Schroeter M, Jander S, Huitinga I, Witte OW, Stoll G. Phagocytic response in photochemically induced infarction of the rat cerebral cortex: the role of resident microglia. Stroke 1997; 28:382–386.

    CAS  PubMed  Google Scholar 

  59. Kim IS, Gautam SC, Chopp M, Zalonga C, Jones ML, Ward PA, Welch KM. Expression of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 after focal cerebral ischemia in the rat. J Neuroimmunol 1995; 56:127–134.

    CAS  PubMed  Google Scholar 

  60. Wang X, Yue TL, White RF, Barone FC, Feuerstein GZ. Monocyte chemoattractant protein-1 messenger RNA expression in rat ischemic cortex. Stroke 1995; 26:661–665.

    CAS  PubMed  Google Scholar 

  61. Gourmala NG, Buttini M, Limonta S, Sauter A, Boddeke HW. Differential and time-dependent expression of monocyte chemoattractant protein-1 mRNA by astrocytes and macrophages in rat brain: effects of ischemia and peripheral lipopolysaccharide administration. J Neuroimmunol 1997; 74:35–44.

    CAS  PubMed  Google Scholar 

  62. Schroeter M, Jander S, Huitinga I, Stoll G. CD8+ phagocytes in focal ischemia of the rat brain: Predominant origin from hematogenous macrophages and targeting to areas of pannecrosis. Acta Neuropathol 2001; 101:440–448.

    CAS  PubMed  Google Scholar 

  63. Jander S, Schroeter M, D«Urso D, Gillen C, Witte OW, Stoll G. Focal cerebral ischemia of the rat brain elicits an unusual inflammatory response: early appearance of CDS+ macrophages/microglia. Eur J Neurosci 1998; 10:680–688.

    CAS  PubMed  Google Scholar 

  64. Lawetzky A, Tiefenthaler G, Kubo R, H nig T. Identification and characterization or rat T cell populations expressing T cell receptors a/ß and y/S. Eur J Immunol 1990; 20:343–349.

    CAS  PubMed  Google Scholar 

  65. Perry VH, Gordon S. Modulation of CD4 antigen on macrophages and microglia in rat brain. J Exp Med 1987; 166:1138–1143.

    CAS  PubMed  Google Scholar 

  66. Perry VH, Andersson PB, Gordon S. Macrophages and inflammation in the central nervous system. Trends Neurosci 1993; 16:268–273.

    CAS  PubMed  Google Scholar 

  67. Hirji N, Lin TJ, Bissonnette E, Belosevic M, Befus AD. Mechanisms of macrophage stimulation through CD8: Macrophage CDS alpha and CD8 beta induce nitric oxide production and associate killing of the parasite Leishmani major. J Immunol 1998;160:6004–6011.

    CAS  PubMed  Google Scholar 

  68. Hirji N, Lin TJ, Gichrist M, Nault G, Nohara O, Grill BJ et al. Novel CD8 molecule on macrophages and masT cells: expression, function and signaling. Int Arch Allergy Immunol 1999; 118:180–182.

    CAS  PubMed  Google Scholar 

  69. Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koistinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA 1998; 95:15769–15774.

    CAS  PubMed  Google Scholar 

  70. Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci USA 1999; 96:13496–13500.

    CAS  PubMed  Google Scholar 

  71. Arvin B, Neville LF, Barone FC, Feuerstein GZ. The role of inflammation and cytokines in brain injury. Neurosci Biobehav Reviews 1996; 20:445–452.

    CAS  Google Scholar 

  72. Barone FC, Arvin B, White RF, Miller A, Web CL, Willette RN et al. Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 1997; 28:1233–1244.

    CAS  PubMed  Google Scholar 

  73. Peters O, Back T, Lindauer U, Busch C, Megow D, Dreier J et al. Increased formation of reactive oxygen species after permanent and reversible middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 1998; 18:196–205.

    CAS  PubMed  Google Scholar 

  74. Davis CA, Loddick SA, Toulmond S, Stroemer RP, Hunt J, Bothwell NJ. The progression and topographic distribution of interleukin-l????? expression after permanent middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 1999; 19:87–98.

    Google Scholar 

  75. Shohami E, Ginis I, Hallenbeck JM. Dual role of tumor necrosis factor alpha in brain injury. Cytokine Growth Factor Rev 1999; 10:119–130.

    CAS  PubMed  Google Scholar 

  76. Touzani O, Boutin H, Chuquet J, Rothwell N. Potential mechanisms of interleukin-1 involvement in cerebral ischemia. J Neuroimmunol 1999; 100:203–215.

    CAS  PubMed  Google Scholar 

  77. Gregersen R, Lambertsen K, Finsen B. Microglia and macrophages are the major source of tumor necrosis factor in permanent middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab 2000; 20:53–65.

    CAS  PubMed  Google Scholar 

  78. Liu T, McDonnell PC, Young PR, White RF, Siren AL, Hallenbeck JM et al. Interleukin-I mRNA expression in ischemic rat cortex. Stroke 1993; 24:1746–51

    CAS  PubMed  Google Scholar 

  79. Buttini M, Sauter A, Boddeke BW. Induction of interleukin-1 beta mRNA after focal cerebral ischemia in the rat. Brain Res 1994; 23:126–134.

    CAS  Google Scholar 

  80. Jander S, Schroeter M, Stoll G. Role of NMDA receptor signalling in the regulation of inflammatory gene expression after focal brain ischemia. J Neuroimmunol 2000; 109:181–187.

    CAS  PubMed  Google Scholar 

  81. Wang X, Barone FC, Aiyar NV et al. Interleukin-1 receptor and receptor antagonist gene expression after focal stroke in rats. Stroke 1997; 28:155–161

    CAS  PubMed  Google Scholar 

  82. Zhang ZG, Chopp M, Goussev A. Cerebral vessels express interleukin 1 beta after focal ischemia. Brain Res 1998; 784:210–217.

    CAS  PubMed  Google Scholar 

  83. Jander S, Schroeter M, Peters O, Witte OW, Stoll G. Cortical spreading expression induces proinflammatory cytokine gene expression in the rat brain. J Cerebr Blood Flow Metabol 2001; 21:218–225.

    CAS  Google Scholar 

  84. Rothwell NJ, Luheshi GN. Interleukin 1 in the brain: Biology, pathology and therapeutic target. Trends Neurosci 2000; 23:618–625.

    CAS  PubMed  Google Scholar 

  85. Yamasaki Y, Matsuura N, Shozuhara H, Onodera H, Itoyama Y, Kogure K. Interleukin-1 as a pathogenic mediator of ischemic brain damage in rats. Stroke 1995; 26:676–680

    CAS  PubMed  Google Scholar 

  86. Stroemer RF, Rothwell NJ. Exacerbation of ischemic brain damage by localized striatal injection of interlekin-1 beta in the rat. J Cereb Blood Flow Metabol 1998; 18:833–839.

    CAS  Google Scholar 

  87. Relton JK, Rothwell NJ. Interleukin-1 receptor antagonist inhibits ischemic and excitotoxic neuronal damage in the rat. Brain Res Bull 1992; 29:243–246.

    CAS  PubMed  Google Scholar 

  88. Garcia JH, Liu KF, Relton JK. Interleukin-1 receptor antagonist decreases the number of necrotic neurons in rats with middle cerebral artery occlusion. Am J Pathol 1995; 147:1477–1486

    CAS  PubMed  Google Scholar 

  89. Relton JK, Martin D, Thompson RC, Russell DA. Peripheral administration of interleukin-1 receptor antagonist inhibits brain damage after focal ischemica in the rat. Exp Neurol 1996; 138:206–213.

    CAS  PubMed  Google Scholar 

  90. Loddick SA, MacKenzie A, Rothwell NJ. An ICE inhibitor, z-VAD-DCB attenuates ischemic brain damage in the rat. NeuroReport 1996; 7:1465–1468.

    CAS  PubMed  Google Scholar 

  91. Hara H, Friedlander RM, Gagliardini V, Ayata C, Ayata G, Huang Z et al. Inhibition of ICE family proteases reduces ischemic and excitotoxic neuronal damage. Proc Natl Acad Sci USA 1997; 94:2007–2012.

    CAS  PubMed  Google Scholar 

  92. Rabuffetti M, Sciorati C, Tarozzo G, Clementi E, Manfredi AA, Beltramo M. Inhibition of caspase-1-like acitivty by Ac-Tyr-Val-Ala-Asp-Chloromethyl ketone induces long-lasting neuroprotection in cerebral ischeami through appotosis reduction and decrease of proinflammatory cytokines. J Neurosci 2000; 20:4398–4404.

    CAS  PubMed  Google Scholar 

  93. Liu T, Clark RK, McDonell PC, Young PR, White RF, Barone FC et al. Tumor necrosis factor-a expression in ischemic neurons. Stroke 1994; 25:1481–1488.

    CAS  PubMed  Google Scholar 

  94. Botchina GI, Meistrell ME, Botchina IL, Tracey KJ. Expression of TNF and TNF receptors (p55 and p75) in the rat brain after focal cerebral ischemia. Mol Med 1997; 3:765–781.

    Google Scholar 

  95. Fehsel K, Kolb-Bachofen V, Kolb H. Analysis of TNF-a induced DNA strand breaks at the single cell level. Am J Pathol 1991; 139:251–254.

    CAS  PubMed  Google Scholar 

  96. Meirstrell III ME, Botchkina GI, Wang. Tumor necrosis factor alpha is a brain damaging cytokine in cerebral ischemia. Shock 1997; 8:341–348.

    Google Scholar 

  97. Lecker R, Shohami E, Abramsky O. Daxanabiolol, a novel neuroprotective drug in experimental focal ischemia. J Neurol Sci 1999; 162:114–119.

    Google Scholar 

  98. Lavine SD, Hofman FM, Zlokovic By. Circulating antibody against tumor necrosis factor alpha protects rat brain from reperfusion injury. J Cereb Blood Flow Metab 1998; 18:52–58.

    CAS  PubMed  Google Scholar 

  99. Nawashiro H, Martin D, Hallenbeck JM. Inhibition of tumor necrosis factor and amelioration of brain infarction in mice. J Cereb Blood Flow mMetab 1997; 17:229–232.

    CAS  Google Scholar 

  100. Pulsinelli WA, Brierly JB, Plum F. Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 1982; 11:491–498.

    CAS  PubMed  Google Scholar 

  101. Ordy JM, Wengenack TM, Bialobok P, Rodier P, Daggs RB, Dunlap WP et al. Selective vulnerability and early progression of hippocampal CAI pyramidal cell degeneration and GFAP-positive astrocytes reactivity in the rat four-vessel occlusion model of transient global ischemia. Exp Neurol 1993; 119:128–139.

    CAS  PubMed  Google Scholar 

  102. Morioka T, Kalehua AN, Streit WJ. The microglial reaction in the rat dorsal hippocampus following transient forebrain ischemia. J Cereb Blood Flow Metabol 1991; 11:966–973.

    CAS  Google Scholar 

  103. Morioka T, Kalehua AN, Streit WJ. Progressive expression of immunomolecules on microglial cells in the rat dorsal hippocampus following transient forebrain ischemia. Acta Neuropath (Berl) 1992; 83:149–157.

    CAS  Google Scholar 

  104. Finsen BR, Jorgensen MB, Diemer NH, Zimmer J. Microglial MIIC antigen expression after ischemic and kainic acid lesions of the adult rat hippocampus. Glia 1993; 7:41–49.

    CAS  PubMed  Google Scholar 

  105. Jorgensen MB, Finsen BR, Jensen MB, Castellano B, Diemer NH, Zimmer J. Microglial and astroglial reactions to ischemic and kainic acid-induced lesions of the adult rat hippocampus. Exp Neurol 1993; 120:70–88.

    CAS  PubMed  Google Scholar 

  106. Sch fer MK, Schwaeble WJ, Post C, Salvati P, Calabresi M, Sim RB et al. Complement Clq is dramatically up-regulated in brain microglia in response to transient global cerebral ischemia. J Immunol 2000; 164:5444–5452.

    Google Scholar 

  107. Friedlander RM, Gagliardini V, Hara H, Fink KB, Li W, MacDonald G et al. Expression of a dominant negative mutant of interleukin-1 beta converting enzyme in transgenic mice prevents neuronal cell death induced by trophic factor withdrawl and ischemic brain injury. J Exp Med 1997; 185:933–940.

    CAS  PubMed  Google Scholar 

  108. Lin B, Ginsberg MD, Busto R, Dietrich WD. Sequential analysis of subacute and chronic neuronal, astrocytic and microglial alterations after transient global ischemia in rats. Acta Neuropath 1998; 95:511–523.

    CAS  PubMed  Google Scholar 

  109. Yamashita K, Kataoka Y, Yamashita YS, Himeno A, Tsutsumi K, Niwa M et al. Glial endothelia/nitric oxide system participates in hippocampus CAI neuronal death of SHRPS following transient forebrain ischemia. Clin Exp Pharmacol Physiol 1995; 22(suppl. 1):S227–278.

    Google Scholar 

  110. Yamashita K, Kataoka Y, Sakurai-Yamashita Y, Shigematsu K, Himeno A, Niwa M et al. Involvement of glial endothelin/nitric oxide in delayed neuronal death of rat hippocampus after transient forebrain ischemia. Cell Mol Neurobiol 2000; 20:541–551.

    CAS  PubMed  Google Scholar 

  111. Lehrmann E, Christensen T, Zimmer J, Diemer NH, Finsen B. Microglial and macrophage reactions mark progressive changes and define the penumbra in the rat neocortex and striatum after transient middle cerebral artery occlusion. J Comp Neurol 1997; 386:461–476.

    CAS  PubMed  Google Scholar 

  112. Endres M, Namura S, Shimizu-Sasamata M, Waeber C, Zhang L, Gomez-Isla T et al. Attenuation of delayed neuronal death after mild focal ischemia in mice by inhibition of the raspase family. J Cereb Blood Flow Metabol 1998; 18:238–247.

    CAS  Google Scholar 

  113. Chen J, Simon R. Ischemic tolerance in brain. Neurology 1997; 48:306–311.

    CAS  PubMed  Google Scholar 

  114. Schroeter M, Schiene K, Kraemer M, Hagemann G, Weigel H, Eysel UT et al. Astroglial responses in photochemically induced focal ischemia of the rat cortex. Exp Brain Res 1995; 106:1–6.

    CAS  PubMed  Google Scholar 

  115. Schroeter M, Jander S, Witte OW, Stoll G. Hetereogeneity of the microglial response in photochemically induced focal ischemia of the rat cerebral cortex. Neuroscience 1999; 89:1367–1377.

    CAS  PubMed  Google Scholar 

  116. Yamashita K, Vogel P, Fritze K, Back T, Hossmann KA, Wiessner C. Monitoring the temporal and spatial activation pattern of astrocytes in focal cerebral ishcmeia using in situ hybridization to DFAP mRNA: comparison with sgp-2 and Hsp70 mRNA and the effect of glutamate receptor antagonists. Brain Res 1996; 735:285–297.

    CAS  PubMed  Google Scholar 

  117. Hewett Si, Csernansky CA, Choi DW. Selective potentiation of NMDA-induced neuronal injury following induction of astrocytic iNOS. Neuron 194; 13:487–494.

    Google Scholar 

  118. Dietrich D, Feng ZC, Leistra H, Watson BD, Rosenthal M. Photothrombotic infarction triggers multiple episodes of cortical spreading depression in distant brain regions. J Cereb Blood Flow Metab 1994; 14:20–28.

    CAS  PubMed  Google Scholar 

  119. Martins-Ferreira H, Nedergaard M, Nicholson C. Perspectives on spreading depression. Brain Res Brain Res Rev 2000; 32:215–234.

    CAS  PubMed  Google Scholar 

  120. Kobayashi S, Harris VA, Welsh FA. Spreading depression induces tolerance of cortical neurons to ischemia in rat brain. J Cereb Blood Flow Metab 1995; 15:721–727.

    CAS  PubMed  Google Scholar 

  121. Yanamoto H, Hashimoto N, Nagata I, Kikuchi H. Infarct tolerance against temporary focal ischemia following spreading depression in rat brain. Brain Res 1998; 784:239–249.

    CAS  PubMed  Google Scholar 

  122. Lauritzen M, Hansen A.I. The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression. J Cereb Blood Flow Metab 1992; 12:223–229

    CAS  PubMed  Google Scholar 

  123. Ohtsuki T, Ruetzeler CA, Tasaki K, Hallenbeck JM. Interleukin-1 mediates induction of tolerance to global ischemia in gerbil hippocampal CAI neurons. J Cereb Blood Flow Metab 1996; 16:1137–1142.

    CAS  PubMed  Google Scholar 

  124. Mattson MP. Neuroprotective signal transduction: relevance to stroke. Neurosci Biobehav Rev 1997; 21:193–206.

    CAS  PubMed  Google Scholar 

  125. Ginis I, Schweizer U, Brenner M, Liu J, Azzam N, Spatz M et al. TNF-a pretreatment prevents subsequent activation of cultured brain cells with TNF-a and hypoxia via ceramide. Am J Physiol 1999; 45:C1171–C1183.

    Google Scholar 

  126. Liu J, Ginis I, Spatz M, Hallenbeck JM. Hypoxie preconditioning protects cultured neurons against hypoxic stress via TNF-a and ceramide. Am J Physiol Cell Pysiol 2000; 278:C144–C153.

    CAS  Google Scholar 

  127. Wang X, Li X, Erhardt JA, Barone FC, Feuerstein GZ. Detection of tumor necrosis factor-alpha mRNA induction in ischemic brain tolerance by means of real-time polymerase chain reaction. J Cereb Blood Flow Metab 2000; 20:15–20.

    PubMed  Google Scholar 

  128. Tasaki K, Ruetzeler CA, Ohtsuki T, Martin D, Nawashiro H, Hallenbeck JM. Lipopolysaccharide pretreatment induces resistance against subsequent focal cerebral ischemic damage in spontaneously hypertensive rats. Brain Res 1997; 748:267–270.

    CAS  PubMed  Google Scholar 

  129. Bruce AJ, Boling W, Kindy MS et al. Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. Nat Med 1996; 2:788–794.

    CAS  PubMed  Google Scholar 

  130. Gary DS, Bruce-Keller AJ, Kindy MS, Mattson MP. Ischemic and excitotoxic brain injury is enhanced in mice lacking the p55 tumor necrosis factor receptor. J Cereb Blood Flow Metabol 1998; 18:1283–1287.

    CAS  Google Scholar 

  131. Scherbel U, Raghupathi R, Nakamura M, Saatman KE, Trojanowski JQ, Neugebauer E et al. Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury. Proc Natl Acad Sci USA 1999; 96:8721–8726.

    CAS  PubMed  Google Scholar 

  132. Goodmann Y, Mattson MP. Ceramide protects hippocampal neurons agianst excitotoxic and oxidative insults and amyloid-(3-peptide toxicity. J Nemochem 1996; 66:869–872.

    Google Scholar 

  133. Chen Y, Ginis I, Halenbeck JM. The protective effect of ceramide in immature rat brain hypoxia-ischemia involves up-regulation of bel-2 and reduction of TUNEL-positive cells. J Cereb Blood flow Metab 2001; 21:34–40

    PubMed  Google Scholar 

  134. Schneider H, Pitossi F, Balschun D, Wagner A, del Rey A, Besedovsky HO. A neuromodulatory role of interleukin-13 in the hippocampus. Proc Natl Acad Sci USA 1998; 95: 7778–7783.

    CAS  PubMed  Google Scholar 

  135. Hagemann G, Redecker C, Neumann-Haefelin T, Freund IIJ, Witte OW. Increased longterm potentiation in the surround of experimentally induced focal cortical infarction. Ann Neurol 1998; 44:255–258.

    CAS  PubMed  Google Scholar 

  136. Miller A, Lider O, Roberts AB, Spom MB, Weiner HL. Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering. Proc Natl Acad Sci USA 1992; 89:421–425.

    CAS  PubMed  Google Scholar 

  137. Weiner HL, Friedman A, Miller A, Khoury SJ, al-Sabbagh A, Santos L et al. Oral tolerance: Immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Annu Rev Immunol 1994; 12:809–837.

    CAS  PubMed  Google Scholar 

  138. Becker KJ, McCarron RM, Ruetzler C, Laban O, Sternberg E, Flanders KJ et al. Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia. Proc Natl Acad Sci USA 1997; 94:10873–10878

    CAS  PubMed  Google Scholar 

  139. Prehn JH, Backhauss C, Krieglstein J. Transforming growth factor-beta 1 prevents glutamate neurotoxicity in rat neocortical cultures and protects mouse neocortex from ischemic injury in vivo. J Cereb Blood Flow Metab 1993; 13:521–525.

    CAS  PubMed  Google Scholar 

  140. Lehrmann E, Kiefer R, Finsen B, Diemer NH, Zimmer J, Hartung HP. Cytokines in cerebral ischemia: expression of transforming growth factor beta-1 mRNA in the postischemic adult hippocampus. Exp Neurol 1995; 131:1–10.

    Google Scholar 

  141. Lehrmann E, Kiefer R, Christensen T, Toyka KV, Zimmer J, Diemer NH et al. Microglia and macrophages are major sources of locally produced transforming growth factor-betal after transient middle cerebral artery occlusion in rats. Glia 1998; 24°:437–448.

    CAS  PubMed  Google Scholar 

  142. Gross CE, Bednar MM, Howard DB, Spom MB. Transforming growth factor-beta 1 reduces infarct size after experimental cerebral ischemia in a rabbit model. Stroke 1993; 24:558–562.

    CAS  PubMed  Google Scholar 

  143. McNeill H, Williams C, Guan J, Dragunow M, Lawlor P, Sirimanne E et al. Neuronal rescue with transforming growth factor-beta 1 after hypoxic-ischemic brain injury. NeuroReport 1994; 14:901–904

    Google Scholar 

  144. Henrich-Noack P, Prehn JH, Krieglstein J. TGF-beta I protects hippocampal neurons against degeneration caused by transient global ischemia. Dose-response relationship and potential neuroprotective mechanisms. Stroke 1996; 27:1609–1614.

    CAS  PubMed  Google Scholar 

  145. Moalem G, Leibowitz-Amit R, Yoles E, Mor F, Cohen I, Schwartz M. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med 1999; 5:49–55.

    CAS  PubMed  Google Scholar 

  146. Hammarberg H, Lidman O, Lundberg C, Eltayeb SY, Gilen AW, Muhallab S et al. Neuroprotection by encephalomyelitis: rescue of mechanically injured neurons and neurotrophin production by CNS-infiltrating T and natural killer cells. J Neurosci 2000; 120:5283–5291.

    Google Scholar 

  147. Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE et al. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: A neuroprotective role of inflammation?. J Exp Med 1999; 189:865–870.

    CAS  PubMed  Google Scholar 

  148. Stoll G, Mller HW. Nerve injury, axonal degeneration and neural regeneration: Basic insights. Brain Pathol 1999; 9:313–325.

    CAS  PubMed  Google Scholar 

  149. Cajal RY. Cajal«s Degeneration & Regeneration of the Nervous System. Translated by R.M. May, DeFelipe. New York: Oxford University Press, 1991:589.

    Google Scholar 

  150. Aguayo AJ, David S, Richardson P, Bray G. Axon elongation in peripheral and central nervous system transplants. In: Fedoroff S, Hertz L, eds. Advances in Cellular Neurobiology. Vol 3. New York: Academic Press, 1982:215–234.

    Google Scholar 

  151. Bandtlow CE, Schwab ME. NI-35/250/Nogo-A: A neurite growth inhibitor restricting structural plasticity and regeneration of nerve fibers in the adult vertebrate CNS. Glia 2000; 29:175–181.

    CAS  PubMed  Google Scholar 

  152. Qiu J, Cai D, Filbin MT. Ghat inhibition of nerve regeneration in the mature mammalian CNS. Glia 2000; 29:166–174.

    CAS  PubMed  Google Scholar 

  153. Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME. Nogo-A is a myelin-assoicated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 2000; 403:434–439.

    CAS  PubMed  Google Scholar 

  154. GranPr T, Nakamura F, Vartanian T, Strittmatter SM. Identification of the NOGO inhibitor of axons regeneration as a Reticulon protein. Nature 2000; 403:439–444.

    Google Scholar 

  155. Perry VH, Brown MC, Gordon S. The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration. J Exp Med 1987; 165:1218–1223.

    CAS  PubMed  Google Scholar 

  156. Stoll G, Griffin JW, Li CY, Trapp BD. Wallerian degeneration of the peripheral nervous system: Participation of both Schwann cells and macrophages in myelin degradation. J Neurocytol 1989; 18:671–683.

    CAS  PubMed  Google Scholar 

  157. Jander S, Lausberg F, Stoll G. Differential recruitment of CD8+ macrophages during Wallerian degeneration in the peripheral and central nervous system. Brain Pathol 2001; 11:27–38.

    CAS  PubMed  Google Scholar 

  158. Gillen C, Jander S, Stoll G. Sequential expression of mRNA for proinflammatory cytokines and interleukin-10 in the rat peripheral nervous system: comparison between immune-mediated demyelination and Wallerian degeneration. J Neurosci Res 1998; 51:489–496.

    CAS  PubMed  Google Scholar 

  159. Menge T, Jander S, Stoll G. Induction of the proinflammatory cytokine interleukin-l8 by axonal injury. J Neurosci Res 2001; 65:332–339.

    CAS  PubMed  Google Scholar 

  160. Stoll G, Trapp BD, Griffin JW. Macrophage function during Wallerian degeneration of the rat optic nerve: clearance of degenerating myelin and la expression. J Neurosci 1989b; 9:2327–2335.

    CAS  Google Scholar 

  161. George R, Griffin JW. Delayed macrophage responses and myelin clearance during Wallerian degeneration in the central nervous system: The dorsal radiculotomy model. Exp Neurol 1994; 129:225–236.

    CAS  PubMed  Google Scholar 

  162. Bregman BR, Kunkel-Bagden E, Schnell L, Dai HN, Gao D, Schwab ME. Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors. Nature 1995; 378:498–501.

    CAS  PubMed  Google Scholar 

  163. Z«Graggen W, Metz GAS, Kartje GL, Thallamir M, Schwab ME. Functional recovery and enhanced corticofugal plasticity after unilateral pyramidal tract lesion and blockade of myelin-associated neurite growth inhibitors in adult rats. J Neurosci 1998; 18:4744–4757.

    Google Scholar 

  164. Fields RD, Schwab ME, Silver J. Does CNS myelin inhibit axon regeneration? Neuroscientist 1999; 5:12–18.

    CAS  Google Scholar 

  165. Reichert F, Rotshenker S. Deficient activation of microglia during optic nerve degeneration. J Neuroimmunol 1996; 70:153–161.

    CAS  PubMed  Google Scholar 

  166. Lazarov-Spiegeler O, Solomon AS, Schwartz M. Peripheral nerve stimulated macrophages simulate a peripheral nerve-like regenerative response in rat transected otpic nerve Glia,xxx,1998; 24:329–337.

    Google Scholar 

  167. Chamak B, Morandi V, Mallat M. Brain macrophages stimulate neurite outgrowth and regeneration by secreting thrombospondin. J Neurosci Res 1994; 38:221–233.

    CAS  PubMed  Google Scholar 

  168. Rabchevsky AG, Streit WJ. Grafting of cultured microglial cells into the lesioned spinal cord of adult rats enhances neurite outgrowth. J Neurosci Res 1997; 47:34–48.

    CAS  PubMed  Google Scholar 

  169. Singer AJ, Clark RAF. Cutaneous wound healing. New Engl J Med 1999; 341:738–746.

    CAS  PubMed  Google Scholar 

  170. Stichel CC, Muller HW. Experimental strategies to promote axonal regeneration after traumatic central nervous system injury. Prog Neurobiol 1998; 56:119–148.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Heinrich-Heine-Universit t, Noorenstrasse 5, D-40225 D, D sseldorf, Germany

    Stoll Guido, Jander Sebastian & Michael Schroeter

  2. Department of Neurology, Julius-Maximilians-Universit t,Josef-Schneider Str., 11, D-97080W, W rzbur g, Germany

    Stoll Guido

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  1. Institute of Physiology, University of Kiel, Kiel, Germany

    Christian Alzheimer

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Guido, S., Sebastian, J., Schroeter, M. (2003). Detrimental and Beneficial Effects of Injury-Induced Inflammation and Cytokine Expression in the Nervous System. In: Alzheimer, C. (eds) Molecular and Cellular Biology of Neuroprotection in the CNS. Advances in Experimental Medicine and Biology, vol 513. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0123-7_3

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