Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models
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- 作者：Cornelia Schuh (1)
Isabella Wimmer (1)
Simon Hametner (1)
Lukas Haider (1)
Anne-Marie Van Dam (2)
Roland S. Liblau (3)
Ken J. Smith (4)
Lesley Probert (5)
Christoph J. Binder (6)
Jan Bauer (1)
Monika Bradl (1)
Don Mahad (7)
Hans Lassmann (1) - 关键词：Multiple sclerosis ; Experimental autoimmune encephalomyelitis (EAE) ; Oxidative injury ; NADPH oxidase ; Inducible nitric oxide synthase (iNOS) ; Iron
- 刊名：Acta Neuropathologica
- 出版年：2014
- 出版时间：August 2014
- 年：2014
- 卷：128
- 期：2
- 页码：247-266
- 全文大小：3,331 KB
- 参考文献：1. Aboul-Enein F, Weiser P, Hoftberger R, Lassmann H, Bradl M (2006) Transient axonal injury in the absence of demyelination: a correlate of clinical disease in acute experimental autoimmune encephalomyelitis. Acta Neuropathol 111(6):539鈥?47. doi:10.1007/s00401-006-0047-y CrossRef
2. Babbe H, Roers A, Waisman A, Lassmann H, Goebels N, Hohlfeld R, Friese M, Schroder R, Deckert M, Schmidt S, Ravid R, Rajewsky K (2000) Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. J Exp Med 192(3):393鈥?04 CrossRef
3. Barac-Latas V, Suchanek G, Breitschopf H, Stuehler A, Wege H, Lassmann H (1997) Patterns of oligodendrocyte pathology in coronavirus-induced subacute demyelinating encephalomyelitis in the Lewis rat. Glia 19(1):1鈥?2 CrossRef
4. Barnett MH, Prineas JW (2004) Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol 55(4):458鈥?68. doi:10.1002/ana.20016 CrossRef
5. Boche D, Perry VH, Nicoll JA (2013) Review: activation patterns of microglia and their identification in the human brain. Neuropathol Appl Neurobiol 39(1):3鈥?8. doi:10.1111/nan.12011 CrossRef
6. Bogdan C (2001) Nitric oxide and the immune response. Nat Immunol 2(10):907鈥?16. doi:10.1038/ni1001-907 CrossRef
7. Bowern N, Ramshaw IA, Clark IA, Doherty PC (1984) Inhibition of autoimmune neuropathological process by treatment with an iron-chelating agent. J Exp Med 160(5):1532鈥?543 CrossRef
8. Breitschopf H, Suchanek G, Gould RM, Colman DR, Lassmann H (1992) In situ hybridization with digoxigenin-labeled probes: sensitive and reliable detection method applied to myelinating rat brain. Acta Neuropathol 84(6):581鈥?87 CrossRef
9. Brown GC (2007) Mechanisms of inflammatory neurodegeneration: iNOS and NADPH oxidase. Biochem Soc Trans 35(Pt 5):1119鈥?121. doi:10.1042/BST0351119
10. Bruck W, Porada P, Poser S, Rieckmann P, Hanefeld F, Kretzschmar HA, Lassmann H (1995) Monocyte/macrophage differentiation in early multiple sclerosis lesions. Ann Neurol 38(5):788鈥?96. doi:10.1002/ana.410380514 CrossRef
11. Campbell GR, Ziabreva I, Reeve AK, Krishnan KJ, Reynolds R, Howell O, Lassmann H, Turnbull DM, Mahad DJ (2011) Mitochondrial DNA deletions and neurodegeneration in multiple sclerosis. Ann Neurol 69(3):481鈥?92. doi:10.1002/ana.22109 CrossRef
12. Cheret C, Gervais A, Lelli A, Colin C, Amar L, Ravassard P, Mallet J, Cumano A, Krause KH, Mallat M (2008) Neurotoxic activation of microglia is promoted by a nox1-dependent NADPH oxidase. J Neurosci 28(46):12039鈥?2051. doi:10.1523/JNEUROSCI.3568-08.2008 CrossRef
13. Choi SH, Aid S, Kim HW, Jackson SH, Bosetti F (2012) Inhibition of NADPH oxidase promotes alternative and anti-inflammatory microglial activation during neuroinflammation. J Neurochem 120(2):292鈥?01. doi:10.1111/j.1471-4159.2011.07572.x CrossRef
14. Choi SH, Lee DY, Kim SU, Jin BK (2005) Thrombin-induced oxidative stress contributes to the death of hippocampal neurons in vivo: role of microglial NADPH oxidase. J Neurosci 25(16):4082鈥?090. doi:10.1523/JNEUROSCI.4306-04.2005 CrossRef
15. Colton C, Wilcock DM (2010) Assessing activation states in microglia. CNS Neurol Disord: Drug Targets 9(2):174鈥?91 CrossRef
16. Cross AH, Keeling RM, Goorha S, San M, Rodi C, Wyatt PS, Manning PT, Misko TP (1996) Inducible nitric oxide synthase gene expression and enzyme activity correlate with disease activity in murine experimental autoimmune encephalomyelitis. J Neuroimmunol 71(1鈥?):145鈥?53 CrossRef
17. Cross AH, Manning PT, Stern MK, Misko TP (1997) Evidence for the production of peroxynitrite in inflammatory CNS demyelination. J Neuroimmunol 80(1鈥?):121鈥?30 CrossRef
18. Dandekar AA, Anghelina D, Perlman S (2004) Bystander CD8 T-cell-mediated demyelination is interferon-gamma-dependent in a coronavirus model of multiple sclerosis. Am J Pathol 164(2):363鈥?69 CrossRef
19. Dasgupta A, Zheng J, Perrone-Bizzozero NI, Bizzozero OA (2013) Increased carbonylation, protein aggregation and apoptosis in the spinal cord of mice with experimental autoimmune encephalomyelitis. ASN Neuro 5(1):e00111. doi:10.1042/AN20120088
20. Feige E, Mendel I, George J, Yacov N, Harats D (2010) Modified phospholipids as anti-inflammatory compounds. Curr Opin Lipidol 21(6):525鈥?29. doi:10.1097/MOL.0b013e32833f2fcb CrossRef
21. Felts PA, Woolston AM, Fernando HB, Asquith S, Gregson NA, Mizzi OJ, Smith KJ (2005) Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide. Brain 128(Pt 7):1649鈥?666. doi:10.1093/brain/awh516 CrossRef
22. Fenyk-Melody JE, Garrison AE, Brunnert SR, Weidner JR, Shen F, Shelton BA, Mudgett JS (1998) Experimental autoimmune encephalomyelitis is exacerbated in mice lacking the NOS2 gene. J Immunol 160(6):2940鈥?946
23. Ferretti G, Bacchetti T (2011) Peroxidation of lipoproteins in multiple sclerosis. J Neurol Sci 311(1鈥?):92鈥?7. doi:10.1016/j.jns.2011.09.004 CrossRef
24. Fiebiger SM, Bros H, Grobosch T, Janssen A, Chanvillard C, Paul F, Dorr J, Millward JM, Infante-Duarte C (2013) The antioxidant idebenone fails to prevent or attenuate chronic experimental autoimmune encephalomyelitis in the mouse. J Neuroimmunol 262(1鈥?):66鈥?1. doi:10.1016/j.jneuroim.2013.07.002 CrossRef
25. Fischer MT, Sharma R, Lim JL, Haider L, Frischer JM, Drexhage J, Mahad D, Bradl M, van Horssen J, Lassmann H (2012) NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury. Brain 135(Pt 3):886鈥?99. doi:10.1093/brain/aws012 CrossRef
26. Fischer MT, Wimmer I, Hoftberger R, Gerlach S, Haider L, Zrzavy T, Hametner S, Mahad D, Binder CJ, Krumbholz M, Bauer J, Bradl M, Lassmann H (2013) Disease-specific molecular events in cortical multiple sclerosis lesions. Brain 136(Pt 6):1799鈥?815. doi:10.1093/brain/awt110 CrossRef
27. Fonseca-Kelly Z, Nassrallah M, Uribe J, Khan RS, Dine K, Dutt M, Shindler KS (2012) Resveratrol neuroprotection in a chronic mouse model of multiple sclerosis. Front Neurol 3:84. doi:10.3389/fneur.2012.00084 CrossRef
28. Forge JK, Pedchenko TV, LeVine SM (1998) Iron deposits in the central nervous system of SJL mice with experimental allergic encephalomyelitis. Life Sci 63(25):2271鈥?284 CrossRef
29. Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Lassmann H (2009) The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain 132(Pt 5):1175鈥?189. doi:10.1093/brain/awp070 CrossRef
30. Gold R, Linington C, Lassmann H (2006) Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70聽years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 129(Pt 8):1953鈥?971. doi:10.1093/brain/awl075 CrossRef
31. Grzybicki DM, Kwack KB, Perlman S, Murphy SP (1997) Nitric oxide synthase type II expression by different cell types in MHV-JHM encephalitis suggests distinct roles for nitric oxide in acute versus persistent virus infection. J Neuroimmunol 73(1鈥?):15鈥?7 CrossRef
32. Haghikia A, Hohlfeld R, Gold R, Fugger L (2013) Therapies for multiple sclerosis: translational achievements and outstanding needs. Trends Mol Med 19(5):309鈥?19. doi:10.1016/j.molmed.2013.03.004 CrossRef
33. Haider L, Fischer MT, Frischer JM, Bauer J, Hoftberger R, Botond G, Esterbauer H, Binder CJ, Witztum JL, Lassmann H (2011) Oxidative damage in multiple sclerosis lesions. Brain 134(Pt 7):1914鈥?924. doi:10.1093/brain/awr128 CrossRef
34. Hallgren B, Sourander P (1958) The effect of age on the non-haemin iron in the human brain. J Neurochem 3(1):41鈥?1 CrossRef
35. Hametner S, Wimmer I, Haider L, Pfeifenbring S, Bruck W, Lassmann H (2013) Iron and neurodegeneration in the multiple sclerosis brain. Ann Neurol. doi:10.1002/ana.23974
36. Haring JS, Pewe LL, Perlman S (2001) High-magnitude, virus-specific CD4 T-cell response in the central nervous system of coronavirus-infected mice. J Virol 75(6):3043鈥?047. doi:10.1128/JVI.75.6.3043-3047.2001 CrossRef
37. Higashi Y, Segawa S, Matsuo T, Nakamura S, Kikkawa Y, Nishida K, Nagasawa K (2011) Microglial zinc uptake via zinc transporters induces ATP release and the activation of microglia. Glia 59(12):1933鈥?945. doi:10.1002/glia.21235 CrossRef
38. Hoftberger R, Fink S, Aboul-Enein F, Botond G, Olah J, Berki T, Ovadi J, Lassmann H, Budka H, Kovacs GG (2010) Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis. Glia 58(15):1847鈥?857. doi:10.1002/glia.21054 CrossRef
39. Hossain MM, Sonsalla PK, Richardson JR (2013) Coordinated role of voltage-gated sodium channels and the Na/H exchanger in sustaining microglial activation during inflammation. Toxicol Appl Pharmacol. doi:10.1016/j.taap.2013.09.011
40. Kauppinen TM, Higashi Y, Suh SW, Escartin C, Nagasawa K, Swanson RA (2008) Zinc triggers microglial activation. J Neurosci 28(22):5827鈥?835. doi:10.1523/JNEUROSCI.1236-08.2008 CrossRef
41. Kipp M, Clarner T, Dang J, Copray S, Beyer C (2009) The cuprizone animal model: new insights into an old story. Acta Neuropathol 118(6):723鈥?36. doi:10.1007/s00401-009-0591-3 CrossRef
42. Kolasinski J, Stagg CJ, Chance SA, Deluca GC, Esiri MM, Chang EH, Palace JA, McNab JA, Jenkinson M, Miller KL, Johansen-Berg H (2012) A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology. Brain 135(Pt 10):2938鈥?951. doi:10.1093/brain/aws242 CrossRef
43. Koprowski H, Zheng YM, Heber-Katz E, Fraser N, Rorke L, Fu ZF, Hanlon C, Dietzschold B (1993) In vivo expression of inducible nitric oxide synthase in experimentally induced neurologic diseases. Proc Natl Acad Sci USA 90(7):3024鈥?027 CrossRef
44. Korner H, Schliephake A, Winter J, Zimprich F, Lassmann H, Sedgwick J, Siddell S, Wege H (1991) Nucleocapsid or spike protein-specific CD4+ T lymphocytes protect against coronavirus-induced encephalomyelitis in the absence of CD8+ T cells. J Immunol 147(7):2317鈥?323
45. Lassmann H (2011) Review: the architecture of inflammatory demyelinating lesions: implications for studies on pathogenesis. Neuropathol Appl Neurobiol 37(7):698鈥?10. doi:10.1111/j.1365-2990.2011.01189.x CrossRef
46. Lassmann H, Bruck W, Lucchinetti CF (2007) The immunopathology of multiple sclerosis: an overview. Brain Pathol 17(2):210鈥?18. doi:10.1111/j.1750-3639.2007.00064.x CrossRef
47. Lassmann H, van Horssen J, Mahad D (2012) Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol 8(11):647鈥?56. doi:10.1038/nrneurol.2012.168 CrossRef
48. LeVine SM, Maiti S, Emerson MR, Pedchenko TV (2002) Apoferritin attenuates experimental allergic encephalomyelitis in SJL mice. Dev Neurosci 24(2鈥?):177鈥?83 (pii:65694) CrossRef
49. Lijia Z, Zhao S, Wang X, Wu C, Yang J (2012) A self-propelling cycle mediated by reactive oxide species and nitric oxide exists in LPS-activated microglia. Neurochem Int 61(7):1220鈥?230. doi:10.1016/j.neuint.2012.09.002 CrossRef
50. Lim H, Kim D, Lee SJ (2013) Toll-like receptor 2 mediates peripheral nerve injury-induced NADPH oxidase 2 expression in spinal cord microglia. J Biol Chem 288(11):7572鈥?579. doi:10.1074/jbc.M112.414904 CrossRef
51. Lin MT, Hinton DR, Marten NW, Bergmann CC, Stohlman SA (1999) Antibody prevents virus reactivation within the central nervous system. J Immunol 162(12):7358鈥?368
52. Lipton HL, Liang Z, Hertzler S, Son KN (2007) A specific viral cause of multiple sclerosis: one virus, one disease. Ann Neurol 61(6):514鈥?23. doi:10.1002/ana.21116 CrossRef
53. Lopes KO, Sparks DL, Streit WJ (2008) Microglial dystrophy in the aged and Alzheimer鈥檚 disease brain is associated with ferritin immunoreactivity. Glia 56(10):1048鈥?060. doi:10.1002/glia.20678 CrossRef
54. Mahad D, Ziabreva I, Lassmann H, Turnbull D (2008) Mitochondrial defects in acute multiple sclerosis lesions. Brain 131(Pt 7):1722鈥?735. doi:10.1093/brain/awn105 CrossRef
55. Mao P, Manczak M, Shirendeb UP, Reddy PH (2013) MitoQ, a mitochondria-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Biochim Biophys Acta 1832(12):2322鈥?331. doi:10.1016/j.bbadis.2013.09.005 CrossRef
56. Marik C, Felts PA, Bauer J, Lassmann H, Smith KJ (2007) Lesion genesis in a subset of patients with multiple sclerosis: a role for innate immunity? Brain 130(Pt 11):2800鈥?815. doi:10.1093/brain/awm236 CrossRef
57. Meguro R, Asano Y, Odagiri S, Li C, Iwatsuki H, Shoumura K (2007) Nonheme-iron histochemistry for light and electron microscopy: a historical, theoretical and technical review. Arch Histol Cytol 70(1):1鈥?9 CrossRef
58. Misko TP, Trotter JL, Cross AH (1995) Mediation of inflammation by encephalitogenic cells: interferon gamma induction of nitric oxide synthase and cyclooxygenase 2. J Neuroimmunol 61(2):195鈥?04 CrossRef
59. Mitchell KM, Dotson AL, Cool KM, Chakrabarty A, Benedict SH, LeVine SM (2007) Deferiprone, an orally deliverable iron chelator, ameliorates experimental autoimmune encephalomyelitis. Mult Scler 13(9):1118鈥?126. doi:10.1177/1352458507078916 CrossRef
60. Moreno B, Jukes JP, Vergara-Irigaray N, Errea O, Villoslada P, Perry VH, Newman TA (2011) Systemic inflammation induces axon injury during brain inflammation. Ann Neurol 70(6):932鈥?42. doi:10.1002/ana.22550 CrossRef
61. Nam JH, Park KW, Park ES, Lee YB, Lee HG, Baik HH, Kim YS, Maeng S, Park J, Jin BK (2012) Interleukin-13/-4-induced oxidative stress contributes to death of hippocampal neurons in abeta1-42-treated hippocampus in vivo. Antioxid Redox Signal 16(12):1369鈥?383. doi:10.1089/ars.2011.4175 CrossRef
62. Nikic I, Merkler D, Sorbara C, Brinkoetter M, Kreutzfeldt M, Bareyre FM, Bruck W, Bishop D, Misgeld T, Kerschensteiner M (2011) A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med 17(4):495鈥?99. doi:10.1038/nm.2324 CrossRef
63. Okuda Y, Nakatsuji Y, Fujimura H, Esumi H, Ogura T, Yanagihara T, Sakoda S (1995) Expression of the inducible isoform of nitric oxide synthase in the central nervous system of mice correlates with the severity of actively induced experimental allergic encephalomyelitis. J Neuroimmunol 62(1):103鈥?12 CrossRef
64. Palinski W, Horkko S, Miller E, Steinbrecher UP, Powell HC, Curtiss LK, Witztum JL (1996) Cloning of monoclonal autoantibodies to epitopes of oxidized lipoproteins from apolipoprotein E-deficient mice. Demonstration of epitopes of oxidized low density lipoprotein in human plasma. J Clin Invest 98(3):800鈥?14. doi:10.1172/JCI118853 CrossRef
65. Park KW, Baik HH, Jin BK (2008) Interleukin-4-induced oxidative stress via microglial NADPH oxidase contributes to the death of hippocampal neurons in vivo. Curr Aging Sci 1(3):192鈥?01 CrossRef
66. Park KW, Baik HH, Jin BK (2009) IL-13-induced oxidative stress via microglial NADPH oxidase contributes to death of hippocampal neurons in vivo. J Immunol 183(7):4666鈥?674. doi:10.4049/jimmunol.0803392 CrossRef
67. Pedchenko TV, LeVine SM (1998) Desferrioxamine suppresses experimental allergic encephalomyelitis induced by MBP in SJL mice. J Neuroimmunol 84(2):188鈥?97 CrossRef
68. Perry VH, Teeling J (2013) Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. Semin Immunopathol 35(5):601鈥?12. doi:10.1007/s00281-013-0382-8 CrossRef
69. Pewe L, Haring J, Perlman S (2002) CD4 T-cell-mediated demyelination is increased in the absence of gamma interferon in mice infected with mouse hepatitis virus. J Virol 76(14):7329鈥?333 CrossRef
70. Pewe L, Perlman S (2002) Cutting edge: CD8 T cell-mediated demyelination is IFN-gamma dependent in mice infected with a neurotropic coronavirus. J Immunol 168(4):1547鈥?551 CrossRef
71. Piddlesden S, Lassmann H, Laffafian I, Morgan BP, Linington C (1991) Antibody-mediated demyelination in experimental allergic encephalomyelitis is independent of complement membrane attack complex formation. Clin Exp Immunol 83(2):245鈥?50 CrossRef
72. Prineas JW, Kwon EE, Cho ES, Sharer LR, Barnett MH, Oleszak EL, Hoffman B, Morgan BP (2001) Immunopathology of secondary-progressive multiple sclerosis. Ann Neurol 50(5):646鈥?57 CrossRef
73. Qi X, Lewin AS, Sun L, Hauswirth WW, Guy J (2007) Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis. Invest Ophthalmol Vis Sci 48(2):681鈥?91. doi:10.1167/iovs.06-0553 CrossRef
74. Qin J, Goswami R, Balabanov R, Dawson G (2007) Oxidized phosphatidylcholine is a marker for neuroinflammation in multiple sclerosis brain. J Neurosci Res 85(5):977鈥?84. doi:10.1002/jnr.21206 CrossRef
75. Rackova L (2013) Cholesterol load of microglia: contribution of membrane architecture changes to neurotoxic power? Arch Biochem Biophys 537(1):91鈥?03. doi:10.1016/j.abb.2013.06.015 CrossRef
76. Raivich G, Bohatschek M, Kloss CU, Werner A, Jones LL, Kreutzberg GW (1999) Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function. Brain Res Brain Res Rev 30(1):77鈥?05 CrossRef
77. Rathore KI, Kerr BJ, Redensek A, Lopez-Vales R, Jeong SY, Ponka P, David S (2008) Ceruloplasmin protects injured spinal cord from iron-mediated oxidative damage. J Neurosci 28(48):12736鈥?2747. doi:10.1523/JNEUROSCI.3649-08.2008 CrossRef
78. Ruuls SR, Bauer J, Sontrop K, Huitinga I, t Hart BA, Dijkstra CD (1995) Reactive oxygen species are involved in the pathogenesis of experimental allergic encephalomyelitis in Lewis rats. J Neuroimmunol 56(2):207鈥?17 CrossRef
79. Sahrbacher UC, Lechner F, Eugster HP, Frei K, Lassmann H, Fontana A (1998) Mice with an inactivation of the inducible nitric oxide synthase gene are susceptible to experimental autoimmune encephalomyelitis. Eur J Immunol 28(4):1332鈥?338. doi:10.1002/(SICI)1521-4141(199804)28:04<1332:AID-IMMU1332>3.0.CO;2-G CrossRef
80. Saxena A, Bauer J, Scheikl T, Zappulla J, Audebert M, Desbois S, Waisman A, Lassmann H, Liblau RS, Mars LT (2008) Cutting edge: multiple sclerosis-like lesions induced by effector CD8 T cells recognizing a sequestered antigen on oligodendrocytes. J Immunol 181(3):1617鈥?621 CrossRef
81. Schreibelt G, van Horssen J, van Rossum S, Dijkstra CD, Drukarch B, de Vries HE (2007) Therapeutic potential and biological role of endogenous antioxidant enzymes in multiple sclerosis pathology. Brain Res Rev 56(2):322鈥?30. doi:10.1016/j.brainresrev.2007.07.005 CrossRef
82. Schulz K, Vulpe CD, Harris LZ, David S (2011) Iron efflux from oligodendrocytes is differentially regulated in gray and white matter. J Neurosci 31(37):13301鈥?3311. doi:10.1523/JNEUROSCI.2838-11.2011 CrossRef
83. Spitsin SV, Scott GS, Mikheeva T, Zborek A, Kean RB, Brimer CM, Koprowski H, Hooper DC (2002) Comparison of uric acid and ascorbic acid in protection against EAE. Free Radic Biol Med 33(10):1363鈥?371 CrossRef
84. Stohlman SA, Hinton DR, Parra B, Atkinson R, Bergmann CC (2008) CD4 T cells contribute to virus control and pathology following central nervous system infection with neurotropic mouse hepatitis virus. J Virol 82(5):2130鈥?139. doi:10.1128/JVI.01762-07 CrossRef
85. Storch MK, Stefferl A, Brehm U, Weissert R, Wallstrom E, Kerschensteiner M, Olsson T, Linington C, Lassmann H (1998) Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology. Brain Pathol 8(4):681鈥?94 CrossRef
86. Streit WJ, Sammons NW, Kuhns AJ, Sparks DL (2004) Dystrophic microglia in the aging human brain. Glia 45(2):208鈥?12. doi:10.1002/glia.10319 CrossRef
87. Taoufik E, Tseveleki V, Chu SY, Tselios T, Karin M, Lassmann H, Szymkowski DE, Probert L (2011) Transmembrane tumour necrosis factor is neuroprotective and regulates experimental autoimmune encephalomyelitis via neuronal nuclear factor-kappaB. Brain 134(Pt 9):2722鈥?735. doi:10.1093/brain/awr203 CrossRef
88. Tschen SI, Bergmann CC, Ramakrishna C, Morales S, Atkinson R, Stohlman SA (2002) Recruitment kinetics and composition of antibody-secreting cells within the central nervous system following viral encephalomyelitis. J Immunol 168(6):2922鈥?929 CrossRef
89. Van Dam AM, Bauer J, Man AHWK, Marquette C, Tilders FJ, Berkenbosch F (1995) Appearance of inducible nitric oxide synthase in the rat central nervous system after rabies virus infection and during experimental allergic encephalomyelitis but not after peripheral administration of endotoxin. J Neurosci Res 40(2):251鈥?60. doi:10.1002/jnr.490400214 CrossRef
90. van der Goes A, Brouwer J, Hoekstra K, Roos D, van den Berg TK, Dijkstra CD (1998) Reactive oxygen species are required for the phagocytosis of myelin by macrophages. J Neuroimmunol 92(1鈥?):67鈥?5 CrossRef
91. van Horssen J, Singh S, van der Pol S, Kipp M, Lim JL, Peferoen L, Gerritsen W, Kooi EJ, Witte ME, Geurts JJ, de Vries HE, Peferoen-Baert R, van den Elsen PJ, van der Valk P, Amor S (2012) Clusters of activated microglia in normal-appearing white matter show signs of innate immune activation. J Neuroinflamm 9:156. doi:10.1186/1742-2094-9-156 CrossRef
92. Van Strien ME, Baron W, Bakker EN, Bauer J, Bol JG, Breve JJ, Binnekade R, Van Der Laarse WJ, Drukarch B, Van Dam AM (2011) Tissue transglutaminase activity is involved in the differentiation of oligodendrocyte precursor cells into myelin-forming oligodendrocytes during CNS remyelination. Glia 59(11):1622鈥?634. doi:10.1002/glia.21204 CrossRef
93. Wege H, Dorries R (1984) Hybridoma antibodies to the murine coronavirus JHM: characterization of epitopes on the peplomer protein (E2). J Gen Virol 65(Pt 11):1931鈥?942 CrossRef
94. Wege H, Schluesener H, Meyermann R, Barac-Latas V, Suchanek G, Lassmann H (1998) Coronavirus infection and demyelination. Development of inflammatory lesions in Lewis rats. Adv Exp Med Biol 440:437鈥?44 CrossRef
95. Wiendl H, Hohlfeld R (2009) Multiple sclerosis therapeutics: unexpected outcomes clouding undisputed successes. Neurology 72(11):1008鈥?015. doi:10.1212/01.wnl.0000344417.42972.54 CrossRef
96. Wu GF, Perlman S (1999) Macrophage infiltration, but not apoptosis, is correlated with immune-mediated demyelination following murine infection with a neurotropic coronavirus. J Virol 73(10):8771鈥?780
97. Zimprich F, Winter J, Wege H, Lassmann H (1991) Coronavirus induced primary demyelination: indications for the involvement of a humoral immune response. Neuropathol Appl Neurobiol 17(6):469鈥?84 CrossRef - 作者单位：Cornelia Schuh (1)
Isabella Wimmer (1)
Simon Hametner (1)
Lukas Haider (1)
Anne-Marie Van Dam (2)
Roland S. Liblau (3)
Ken J. Smith (4)
Lesley Probert (5)
Christoph J. Binder (6)
Jan Bauer (1)
Monika Bradl (1)
Don Mahad (7)
Hans Lassmann (1)
1. Department of Neuroimmunology, Centre for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090, Vienna, Austria
2. Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands
3. Inserm, U1043, CNRS, Centre de Physiopathologie de Toulouse Purpan (CPTP), U5282, Universit茅 de Toulouse, 31300, Toulouse, France
4. Department of Neuroinflammation, University College London Institute of Neurology, London, UK
5. Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece
6. Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
7. Centre for Neuroregeneration, University of Edinburgh, Edinburgh, UK - ISSN：1432-0533
文摘
Recent data suggest that oxidative injury may play an important role in demyelination and neurodegeneration in multiple sclerosis (MS). We compared the extent of oxidative injury in MS lesions with that in experimental models driven by different inflammatory mechanisms. It was only in a model of coronavirus-induced demyelinating encephalomyelitis that we detected an accumulation of oxidised phospholipids, which was comparable in extent to that in MS. In both, MS and coronavirus-induced encephalomyelitis, this was associated with massive microglial and macrophage activation, accompanied by the expression of the NADPH oxidase subunit p22phox but only sparse expression of inducible nitric oxide synthase (iNOS). Acute and chronic CD4+ T cell-mediated experimental autoimmune encephalomyelitis lesions showed transient expression of p22phox and iNOS associated with inflammation. Macrophages in chronic lesions of antibody-mediated demyelinating encephalomyelitis showed lysosomal activity but very little p22phox or iNOS expressions. Active inflammatory demyelinating lesions induced by CD8+ T cells or by innate immunity showed macrophage and microglial activation together with the expression of p22phox, but low or absent iNOS reactivity. We corroborated the differences between acute CD4+ T cell-mediated experimental autoimmune encephalomyelitis and acute MS lesions via gene expression studies. Furthermore, age-dependent iron accumulation and lesion-associated iron liberation, as occurring in the human brain, were only minor in rodent brains. Our study shows that oxidative injury and its triggering mechanisms diverge in different models of rodent central nervous system inflammation. The amplification of oxidative injury, which has been suggested in MS, is only reflected to a limited degree in the studied rodent models.