The benefits and detriments of macrophages/microglia in models of multiple sclerosis

Clinical and Developmental Immunology

Volumn 2013, Issue , 2013, Pages

  Rawji, Khalil S ^a,b   Yong, V Wee ^a,b  

^a UNIVERSITY OF CALGARY   (Canada)

^b UNIVERSITY OF CALGARY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BETA1A INTERFERON; BRAIN DERIVED NEUROTROPHIC FACTOR; CD16 ANTIGEN; CD86 ANTIGEN; CUPRIZONE; FAS LIGAND; FUMARIC ACID DIMETHYL ESTER; GELATINASE A; GELATINASE B; GLATIRAMER; INTERFERON BETA SERINE; INTERLEUKIN 10; INTERLEUKIN 1BETA; LYSOPHOSPHATIDYLCHOLINE; MANNOSE RECEPTOR; MITOXANTRONE; NOVATRONE; ONCOMODULIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; IMMUNOLOGIC FACTOR;

ADAPTIVE IMMUNITY; ALZHEIMER DISEASE; CELL DIFFERENTIATION; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; COGNITIVE DEFECT; CORPUS CALLOSUM; CYTOKINE RELEASE; DEMYELINATION; HISTOPATHOLOGY; HUMAN; INFLAMMATION; MACROPHAGE; MICROGLIA; MULTIPLE SCLEROSIS; NERVE REGENERATION; NONHUMAN; PRIORITY JOURNAL; REMYELINIZATION; REVIEW; SPINAL CORD INJURY; ANIMAL; CELL MOTION; CENTRAL NERVOUS SYSTEM; CHEMICALLY INDUCED; DEMYELINATING DISEASES; DISEASE MODEL; DRUG EFFECTS; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; IMMUNOLOGY; NERVE CELL; OLIGODENDROGLIA; PATHOLOGY; T LYMPHOCYTE; CHEMICALLY INDUCED DISORDER; DEMYELINATING DISEASE; DRUG EFFECT; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;

ANIMALS; CELL MOVEMENT; CENTRAL NERVOUS SYSTEM; CUPRIZONE; DEMYELINATING DISEASES; DISEASE MODELS, ANIMAL; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; HUMANS; IMMUNOLOGIC FACTORS; LYSOPHOSPHATIDYLCHOLINES; MACROPHAGES; MICROGLIA; MULTIPLE SCLEROSIS; NEURONS; OLIGODENDROGLIA; T-LYMPHOCYTES;

EID: 84880162763     PISSN: 17402522     EISSN: 17402530     Source Type: Journal    
DOI: 10.1155/2013/948976     Document Type: Review

References (138)

1. Shechter R., Schwartz M., Harnessing monocyte-derived macrophages to control central nervous system pathologies: no longer if 'but how'. Journal of Pathology 2013 229 2 332 346 10.1002/path.4106
2. David S., Kroner A., Repertoire of microglial and macrophage responses after spinal cord injury. Nature Reviews Neuroscience 2011 12 7 388 399 2-s2.0-79959379095 10.1038/nrn3053
3. Prinz M., Priller J., Sisodia S. S., Ransohoff R. M., Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nature Neuroscience 2011 14 10 1227 1235 10.1038/nn.2923
4. Ransohoff R. M., Cardona A. E., The myeloid cells of the central nervous system parenchyma. Nature 2010 468 7321 253 262 2-s2.0-78149435065 10.1038/nature09615
5. Saijo K., Glass C. K., Microglial cell origin and phenotypes in health and disease. Nature Reviews Immunology 2011 11 11 775 787 10.1038/nri3086
6. Graeber M. B., Changing face of microglia. Science 2010 330 6005 783 788 2-s2.0-78149322599 10.1126/science.1190929
7. Kierdorf K., Erny D., Goldmann T., Sander V., Schulz C., Perdiguero E. G., Wieghofer P., Heinrich A., Riemke P., Holscher C., Muller D. N., Luckow B., Brocker T., Debowski K., Fritz G., Opdenakker G., Diefenbach A., Biber K., Heikenwalder M., Geissmann F., Rosenbauer F., Prinz M., Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nature Neuroscience 2013 16 3 273 280 10.1038/nn.3318
8. Schulz C., Gomez Perdiguero E., Chorro L., Szabo-Rogers H., Cagnard N., Kierdorf K., Prinz M., Wu B., Jacobsen S. E., Pollard J. W., Frampton J., Liu K. J., Geissmann F., A lineage of myeloid cells independent of myb and hematopoietic stem cells. Science 2012 335 6077 86 90 10.1126/science.1219179
9. Ginhoux F., Greter M., Leboeuf M., Nandi S., See P., Gokhan S., Mehler M. F., Conway S. J., Ng L. G., Stanley E. R., Samokhvalov I. M., Merad M., Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 2010 330 6005 841 845 2-s2.0-78149360132 10.1126/science.1194637
10. Alliot F., Godin I., Pessac B., Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Developmental Brain Research 1999 117 2 145 152 2-s2.0-0032737272 10.1016/S0165-3806(99) 00113-3 (Pubitemid 29531505)
11. Aguzzi A., Barres B. A., Bennett M. L., Microglia: scapegoat, saboteur, or something else? Science 2013 339 6116 156 161 10.1126/science.1227901
12. Ousman S. S., Kubes P., Immune surveillance in the central nervous system. Nature Neuroscience 2012 15 8 1096 1101 10.1038/nn.3161
13. Ajami B., Bennett J. L., Krieger C., Tetzlaff W., Rossi F. M. V., Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nature Neuroscience 2007 10 12 1538 1543 2-s2.0-36448994709 10.1038/nn2014 (Pubitemid 350175883)
14. Ajami B., Bennett J. L., Krieger C., McNagny K. M., Rossi F. M., Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nature Neuroscience 2011 14 9 1142 1150 10.1038/nn.2887
15. Streit W. J., Graeber M. B., Kreutzberg G. W., Functional plasticity of microglia: a review. Glia 1988 1 5 301 307 2-s2.0-0024199439
16. Mantovani A., Sica A., Sozzani S., Allavena P., Vecchi A., Locati M., The chemokine system in diverse forms of macrophage activation and polarization. Trends in Immunology 2004 25 12 677 686 2-s2.0-7644231561 10.1016/j.it.2004.09. 015 (Pubitemid 39457982)
17. Martinez F. O., Helming L., Gordon S., Alternative activation of macrophages: an immunologic functional perspective. Annual Review of Immunology 2009 27 451 483 2-s2.0-67650485985 10.1146/annurev.immunol.021908.132532
18. Mantovani A., Biswas S. K., Galdiero M. R., Sica A., Locati M., Macrophage plasticity and polarization in tissue repair and remodelling. Journal of Pathology 2013 229 2 176 185 10.1002/path.4133
19. Kigerl K. A., Gensel J. C., Ankeny D. P., Alexander J. K., Donnelly D. J., Popovich P. G., Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. Journal of Neuroscience 2009 29 43 13435 13444 2-s2.0-70350558453 10.1523/JNEUROSCI.3257-09.2009
20. Lucchinetti C., Bruck W., Parisi J., Scheithauer B., Rodriguez M., Lassmann H., Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Annals of Neurology 2000 47 6 707 717 10.1002/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q (Pubitemid 30390191)
21. Prineas J. W., Wright R. G., Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. Laboratory Investigation 1978 38 4 409 421 2-s2.0-0018098512 (Pubitemid 8338235)
22. Letellier E., Kumar S., Sancho-Martinez I., Krauth S., Funke-Kaiser A., Laudenklos S., Konecki K., Klussmann S., Corsini N. S., Kleber S., Drost N., Neumann A., Levi-Strauss M., Brors B., Gretz N., Edler L., Fischer C., Hill O., Thiemann M., Biglari B., Karray S., Martin-Villalba A., CD95-ligand on peripheral myeloid cells activates Syk kinase to trigger their recruitment to the inflammatory site. Immunity 2010 32 2 240 252 10.1016/j.immuni.2010.01.011
23. Wells J. E. A., Hurlbert R. J., Fehlings M. G., Yong V. W., Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice. Brain 2003 126 7 1628 1637 2-s2.0-0037481943 (Pubitemid 36834939)
24. Sanchez Mejia R. O., Ona V. O., Li M., Friedlander R. M., Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction. Neurosurgery 2001 48 6 1393 1401 2-s2.0-0034998271 (Pubitemid 32472597)
25. Arvin K. L., Han B. H., Du Y., Lin S. Z., Paul S. M., Holtzman D. M., Minocycline markedly protects the neonatal brain against hypoxic-ischemic injury. Annals of Neurology 2002 52 1 54 61 2-s2.0-0036289498 10.1002/ana.10242 (Pubitemid 34693743)
26. Popovich P. G., Guan Z., Wei P., Huitinga I., Van Rooijen N., Stokes B. T., Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Experimental Neurology 1999 158 2 351 365 2-s2.0-0032838089 10.1006/exnr.1999.7118 (Pubitemid 29382826)
27. Takeuchi H., Neurotoxicity by microglia: mechanisms and potential therapeutic strategy. Clinical and Experimental Neuroimmunology 2010 1 1 12 21 2-s2.0-77956322561 10.1111/j.1759-1961.2009.00001.x
28. Rapalino O., Lazarov-Spiegler O., Agranov E., Velan G. J., Yoles E., Fraidakis M., Solomon A., Gepstein R., Katz A., Belkin M., Hadani M., Schwartz M., Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nature Medicine 1998 4 7 814 821 2-s2.0-0031849511 10.1038/nm0798-814 (Pubitemid 28331023)
29. Yin Y., Henzl M. T., Lorber B., Nakazawa T., Thomas T. T., Jiang F., Langer R., Benowitz L. I., Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nature Neuroscience 2006 9 6 843 852 2-s2.0-33745712928 10.1038/nn1701
30. Coull J. A. M., Beggs S., Boudreau D., Boivin D., Tsuda M., Inoue K., Gravel C., Salter M. W., De Koninck Y., BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005 438 7070 1017 1021 2-s2.0-30744439794 10.1038/nature04223 (Pubitemid 43093974)
31. Dougherty K. D., Dreyfus C. F., Black I. B., Brain-derived neurotrophic factor in astrocytes, oligodendrocytes, and microglia/macrophages after spinal cord injury. Neurobiology of Disease 2000 7 6 574 585 2-s2.0-0034525687 10.1006/nbdi.2000.0318 (Pubitemid 32044283)
32. Shechter R., London A., Varol C., Raposo C., Cusimano M., Yovel G., Rolls A., Mack M., Pluchino S., Martino G., Jung S., Schwartz M., Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Medicine 2009 6 7, article e1000113 2-s2.0-68049143269 10.1371/journal.pmed.1000113
33. Schonberg D. L., Goldstein E. Z., Sahinkaya F. R., Wei P., Popovich P. G., McTigue D. M., Ferritin stimulates oligodendrocyte genesis in the adult spinal cord and can be transferred from macrophages to NG2 cells in vivo. The Journal of Neuroscience 2012 32 16 5374 5384 10.1523/JNEUROSCI.3517-11.2012
34. Barrette B., Hébert M. A., Filali M., Lafortune K., Vallières N., Gowing G., Julien J. P., Lacroix S., Requirement of myeloid cells for axon regeneration. Journal of Neuroscience 2008 28 38 9363 9376 2-s2.0-56949098606 10.1523/JNEUROSCI.1447-08.2008
35. El Khoury J., Toft M., Hickman S. E., Means T. K., Terada K., Geula C., Luster A. D., Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nature Medicine 2007 13 4 432 438 2-s2.0-34147115541 10.1038/nm1555 (Pubitemid 46559828)
36. Naert G., Rivest S., CC chemokine receptor 2 deficiency aggravates cognitive impairments and amyloid pathology in a transgenic mouse model of Alzheimer's disease. Journal of Neuroscience 2011 31 16 6208 6220 2-s2.0-79955775349 10.1523/JNEUROSCI.0299-11.2011
37. Grathwohl S. A., Kälin R. E., Bolmont T., Prokop S., Winkelmann G., Kaeser S. A., Odenthal J., Radde R., Eldh T., Gandy S., Aguzzi A., Staufenbiel M., Mathews P. M., Wolburg H., Heppner F. L., Jucker M., Formation and maintenance of Alzheimer's disease beta-amyloid plaques in the absence of microglia. Neuroforum 2009 12 11 1361 1363 2-s2.0-77949368431
38. Simard A. R., Soulet D., Gowing G., Julien J. P., Rivest S., Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron 2006 49 4 489 502 2-s2.0-32344440522 10.1016/j.neuron.2006.01.022 (Pubitemid 43221886)
39. Lassmann H., Brück W., Lucchinetti C., Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends in Molecular Medicine 2001 7 3 115 121 2-s2.0-0035096330 10.1016/S1471-4914(00) 01909-2 (Pubitemid 32201673)
40. Noseworthy J. H., Lucchinetti C., Rodriguez M., Weinshenker B. G., Multiple sclerosis. The New England Journal of Medicine 2000 343 13 938 952 2-s2.0-0034727066 10.1056/NEJM200009283431307
41. Sriram S., Role of glial cells in innate immunity and their role in CNS demyelination. Journal of Neuroimmunology 2011 239 13 20 10.1016/j.jneuroim. 2011.08.012
42. Hemmer B., Archelos J. J., Hartung H. P., New concepts in the immunopathogenesis of multiple sclerosis. Nature Reviews Neuroscience 2002 3 4 291 301 2-s2.0-0036546066 10.1038/nrn784 (Pubitemid 135706608)
43. Ransohoff R. M., Animal models of multiple sclerosis: the good, the bad and the bottom line. Nature Neuroscience 2012 15 8 1074 1077 10.1038/nn.3168
44. Martiney J. A., Rajan A. J., Charles P. C., Cerami A., Ulrich P. C., Macphail S., Tracey K. J., Brosnan C. F., Prevention and treatment of experimental autoimmune encephalomyelitis by CNI-1493, a macrophage-deactivating agent. Journal of Immunology 1998 160 11 5588 5595 2-s2.0-0032103940 (Pubitemid 28267853)
45. Bhasin M., Wu M., Tsirka S. E., Modulation of microglial/macrophage activation by macrophage inhibitory factor (TKP) or tuftsin (TKPR) attenuates the disease course of experimental autoimmune encephalomyelitis. BMC Immunology 2007 8, article 10 2-s2.0-34547763842 10.1186/1471-2172-8-10 (Pubitemid 47226069)
46. Tran E. H., Hoekstra K., Van Rooijen N., Dijkstra C. D., Owens T., Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice. Journal of Immunology 1998 161 7 3767 3775 2-s2.0-0032193213
47. Heppner F. L., Greter M., Marino D., Falsig J., Raivich G., Hövelmeyer N., Waisman A., Rülicke T., Prinz M., Priller J., Becher B., Aguzzi A., Experimental autoimmune encephalomyelitis repressed by microglial paralysis. Nature Medicine 2005 11 2 146 152 2-s2.0-20044376483 10.1038/nm1177 (Pubitemid 40321349)
48. Agrawal S., Anderson P., Durbeej M., Van Rooijen N., Ivars F., Opdenakker G., Sorokin L. M., Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis. Journal of Experimental Medicine 2006 203 4 1007 1019 2-s2.0-33645869560 10.1084/jem.20051342
49. Bartholomäus I., Kawakami N., Odoardi F., Schläger C., Miljkovic D., Ellwart J. W., Klinkert W. E. F., Flügel-Koch C., Issekutz T. B., Wekerle H., Flügel A., Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature 2009 462 7269 94 98 2-s2.0-70449106029 10.1038/nature08478
50. Nikić I., Merkler D., Sorbara C., Brinkoetter M., Kreutzfeldt M., Bareyre F. M., Brück W., Bishop D., Misgeld T., Kerschensteiner M., A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nature Medicine 2011 17 4 495 499 2-s2.0-79953761792 10.1038/nm.2324
51. Rasmussen S., Wang Y., Kivisäkk P., Bronson R. T., Meyer M., Imitola J., Khoury S. J., Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing-remitting experimental autoimmune encephalomyelitis. Brain 2007 130 11 2816 2829 2-s2.0-35649010838 10.1093/brain/awm219 (Pubitemid 350033966)
52. Starossom S. C., Mascanfroni I. D., Imitola J., Cao L., Raddassi K., Hernandez S. F., Bassil R., Croci D. O., Cerliani J. P., Delacour D., Wang Y., Elyaman W., Khoury S. J., Rabinovich G. A., Galectin-1 deactivates classically activated microglia and protects from inflammation-induced neurodegeneration. Immunity 2012 37 2 249 263 10.1016/j.immuni.2012.05.023
53. Mikita J., Dubourdieu-Cassagno N., Deloire M. S., Vekris A., Biran M., Raffard G., Brochet B., Canron M. H., Franconi J. M., Boiziau C., Petry K. G., Altered M1/M2 activation patterns of monocytes in severe relapsing experimental rat model of multiple sclerosis. Amelioration of clinical status by M2 activated monocyte administration. Multiple Sclerosis 2011 17 1 2 15 2-s2.0-78650996588 10.1177/1352458510379243
54. Vaknin I., Kunis G., Miller O., Butovsky O., Bukshpan S., Beers D. R., Henkel J. S., Yoles E., Appel S. H., Schwartz M., Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis. PLoS One 2011 6 11, article e26921 10.1371/journal.pone.0026921
55. Denney L., Kok W. L., Cole S. L., Sanderson S., McMichael A. J., Ho L. P., Activation of invariant NKT cells in early phase of experimental autoimmune encephalomyelitis results in differentiation of Ly6Chi inflammatory monocyte to M2 macrophages and improved outcome. The Journal of Immunology 2012 189 2 551 557 10.4049/jimmunol.1103608
56. Matsushima G. K., Morell P., The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathology 2001 11 1 107 116 2-s2.0-0035198691
57. Silvestroff L., Bartucci S., Soto E., Gallo V., Pasquini J., Franco P., Cuprizone-Induced demyelination in CNP::GFP transgenic mice. Journal of Comparative Neurology 2010 518 12 2261 2283 2-s2.0-77952180125 10.1002/cne.22330
58. Hoffmann K., Lindner M., Gröticke I., Stangel M., Löscher W., Epileptic seizures and hippocampal damage after cuprizone-induced demyelination in C57BL/6 mice. Experimental Neurology 2008 210 2 308 321 2-s2.0-41149091296 10.1016/j.expneurol.2007.11.005
59. Koutsoudaki P. N., Skripuletz T., Gudi V., Moharregh-Khiabani D., Hildebrandt H., Trebst C., Stangel M., Demyelination of the hippocampus is prominent in the cuprizone model. Neuroscience Letters 2009 451 1 83 88 2-s2.0-58249127253 10.1016/j.neulet.2008.11.058
60. Norkute A., Hieble A., Braun A., Johann S., Clarner T., Baumgartner W., Beyer C., Kipp M., Cuprizone treatment induces demyelination and astrocytosis in the mouse hippocampus. Journal of Neuroscience Research 2009 87 6 1343 1355 2-s2.0-65549106959 10.1002/jnr.21946
61. Groebe A., Clarner T., Baumgartner W., Dang J., Beyer C., Kipp M., Cuprizone treatment induces distinct demyelination, astrocytosis, and microglia cell invasion or proliferation in the mouse cerebellum. Cerebellum 2009 8 3 163 174 2-s2.0-69549105728 10.1007/s12311-009-0099-3
62. Pott F., Gingele S., Clarner T., Dang J., Baumgartner W., Beyer C., Kipp M., Cuprizone effect on myelination, astrogliosis and microglia attraction in the mouse basal ganglia. Brain Research 2009 1305 137 149 2-s2.0-73949136916
63. Moharregh-Khiabani D., Blank A., Skripuletz T., Miller E., Kotsiari A., Gudi V., Stangel M., Effects of fumaric acids on cuprizone induced central nervous system de- and remyelination in the mouse. PLoS ONE 2010 5 7, article e11769 2-s2.0-77955478688 10.1371/journal.pone.0011769
64. Skripuletz T., Lindner M., Kotsiari A., Garde N., Fokuhl J., Linsmeier F., Trebst C., Stangel M., Cortical demyelination is prominent in the murine cuprizone model and is strain-dependent. American Journal of Pathology 2008 172 4 1053 1061 2-s2.0-42049109071 10.2353/ajpath.2008.070850 (Pubitemid 351520001)
65. Hiremath M. M., Saito Y., Knapp G. W., Ting J. P. Y., Suzuki K., Matsushima G. K., Microglial/macrophage accumulation during cuprizone-induced demyelination in C57BL/6 mice. Journal of Neuroimmunology 1998 92 1-2 38 49 2-s2.0-0032440093 10.1016/S0165-5728(98)00168-4 (Pubitemid 29015988)
66. Buschmann J. P., Berger K., Awad H., Clarner T., Beyer C., Kipp M., Inflammatory response and chemokine expression in the white matter corpus callosum and gray matter cortex region during cuprizone-induced demyelination. Journal of Molecular Neuroscience 2012 48 1 66 76 10.1007/s12031-012-9773-x
67. Kipp M., Norkus A., Krauspe B., Clarner T., Berger K., van der Valk P., Amor S., Beyer C., The hippocampal fimbria of cuprizone-treated animals as a structure for studying neuroprotection in multiple sclerosis. Inflammation Research 2011 60 8 723 726 10.1007/s00011-011-0339-0
68. Gudi V., Moharregh-Khiabani D., Skripuletz T., Koutsoudaki P. N., Kotsiari A., Skuljec J., Trebst C., Stangel M., Regional differences between grey and white matter in cuprizone induced demyelination. Brain Research 2009 1283 127 138 2-s2.0-67651115860 10.1016/j.brainres.2009.06.005
69. Wergeland S., Torkildsen O., Myhr K. M., Aksnes L., Mork S. J., Bo L., Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. PLoS One 2011 6 10, article e26262 10.1371/journal.pone.0026262
70. Hagemeyer N., Boretius S., Ott C., Von Streitberg A., Welpinghus H., Sperling S., Frahm J., Simons M., Ghezzi P., Ehrenreich H., Erythropoietin attenuates neurological and histological consequences of toxic demyelination in mice. Molecular Medicine 2012 18 628 635
71. Yoshikawa K., Palumbo S., Toscano C. D., Bosetti F., Inhibition of 5-lipoxygenase activity in mice during cuprizone-induced demyelination attenuates neuroinflammation, motor dysfunction and axonal damage. Prostaglandins Leukotrienes and Essential Fatty Acids 2011 85 1 43 52 2-s2.0-79957670752 10.1016/j.plefa.2011.04.022
72. Fan R., Xu F., Previti M. L., Davis J., Grande A. M., Robinson J. K., Van Nostrand W. E., Minocycline reduces microglial activation and improves behavioral deficits in a transgenic model of cerebral microvascular amyloid. Journal of Neuroscience 2007 27 12 3057 3063 2-s2.0-33947545098 10.1523/JNEUROSCI.4371-06.2007 (Pubitemid 46474134)
73. Skripuletz T., Miller E., Moharregh-Khiabani D., Blank A., Pul R., Gudi V., Trebst C., Stangel M., Beneficial effects of minocycline on cuprizone induced cortical demyelination. Neurochemical Research 2010 35 9 1422 1433 2-s2.0-77957851846 10.1007/s11064-010-0202-7
74. Pasquini L. A., Calatayud C. A., Bertone Uña A. L., Millet V., Pasquini J. M., Soto E. F., The neurotoxic effect of cuprizone on oligodendrocytes depends on the presence of pro-inflammatory cytokines secreted by microglia. Neurochemical Research 2007 32 2 279 292 2-s2.0-33846930155 10.1007/s11064-006-9165-0 (Pubitemid 46238874)
75. Bebo B. F., Fyfe-Johnson A., Adlard K., Beam A. G., Vandenbark A. A., Offner H., Low-dose estrogen therapy ameliorates experimental autoimmune encephalomyelitis in two different inbred mouse strains. Journal of Immunology 2001 166 3 2080 2089 2-s2.0-0035253377 (Pubitemid 32114698)
76. Millet V., Moiola C. P., Pasquini J. M., Soto E. F., Pasquini L. A., Partial inhibition of proteasome activity enhances remyelination after cuprizone-induced demyelination. Experimental Neurology 2009 217 2 282 296 2-s2.0-67349144098 10.1016/j.expneurol.2009.03.005
77. McMahon E. J., Cook D. N., Suzuki K., Matsushima G. K., Absence of macrophage-inflammatory protein-1 α delays central nervous system demyelination in the presence of an intact blood-brain barrier. Journal of Immunology 2001 167 5 2964 2971 2-s2.0-0035451440 (Pubitemid 32768933)
78. Olah M., Amor S., Brouwer N., Vinet J., Eggen B., Biber K., Boddeke H. W., Identification of a microglia phenotype supportive of remyelination. Glia 2012 60 2 306 321
79. Jurevics H., Largent C., Hostettler J., Sammond D. W., Matsushima G. K., Kleindienst A., Toews A. D., Morell P., Alterations in metabolism and gene expression in brain regions during cuprizone-induced demyelination and remyelination. Journal of Neurochemistry 2002 82 1 126 136 2-s2.0-0036310558 10.1046/j.1471-4159.2002.00954.x (Pubitemid 34755257)
80. Skripuletz T., Hackstette D., Bauer K., Gudi V., Pul R., Voss E., Berger K., Kipp M., Baumgartner W., Stangel M., Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination. Brain 2013 136, part 1 147 167
81. Arnett H. A., Wang Y., Matsushima G. K., Suzuki K., Ting J. P. Y., Functional genomic analysis of remyelination reveals importance of inflammation in oligodendrocyte regeneration. Journal of Neuroscience 2003 23 30 9824 9832 2-s2.0-0242524481 (Pubitemid 37371596)
82. Arnett H. A., Hellendall R. P., Matsushima G. K., Suzuki K., Laubach V. E., Sherman P., Ting J. P. Y., The protective role of nitric oxide in a neurotoxicant-induced demyelinating model. Journal of Immunology 2002 168 1 427 433 2-s2.0-0036136329 (Pubitemid 34014145)
83. Arnett H. A., Mason J., Marino M., Suzuki K., Matsushima G. K., Ting J. P. Y., TNF α promotes proliferation of oligodendrocyte progenitors and remyelination. Nature Neuroscience 2001 4 11 1116 1122 2-s2.0-0035705454 10.1038/nn738 (Pubitemid 34116557)
84. Morell P., Barrett C. V., Mason J. L., Toews A. D., Hostettler J. D., Knapp G. W., Matsushima G. K., Gene expression in brain during cuprizone-induced demyelination and remyelination. Molecular and Cellular Neurosciences 1998 12 4-5 220 227 2-s2.0-0031761662 10.1006/mcne.1998.0715 (Pubitemid 28536075)
85. Mason J. L., Suzuki K., Chaplin D. D., Matsushima G. K., Interleukin-1 β promotes repair of the CNS. Journal of Neuroscience 2001 21 18 7046 7052 2-s2.0-0035883161
86. Lau L. W., Keough M. B., Haylock-Jacobs S., Cua R., Doring A., Sloka S., Stirling D. P., Rivest S., Yong V. W., Chondroitin sulfate proteoglycans in demyelinated lesions impair remyelination. Annals of Neurology 2012 72 3 419 432
87. Waxman S. G., Kocsis J. D., Nitta K. C., Lysophosphatidyl choline-induced focal demyelination in the rabbit corpus callosum. Light-microscopic observations. Journal of the Neurological Sciences 1979 44 1 45 53 2-s2.0-0018727410 10.1016/0022-510X(79)90221-1 (Pubitemid 10236365)
88. Imai M., Watanabe M., Suyama K., Osada T., Sakai D., Kawada H., Matsumae M., Mochida J., Delayed accumulation of activated macrophages and inhibition of remyelination after spinal cord injury in an adult rodent model: laboratory investigation. Journal of Neurosurgery 2008 8 1 58 66 2-s2.0-37849004130 10.3171/SPI-08/01/058
89. Pavelko K. D., Van Engelen B. G. M., Rodriguez M., Acceleration in the rate of CNS remyelination in lysolecithin-induced demyelination. Journal of Neuroscience 1998 18 7 2498 2505 2-s2.0-0032053402
90. Garay L., Tungler V., Deniselle M. C., Lima A., Roig P., De Nicola A. F., Progesterone attenuates demyelination and microglial reaction in the lysolecithin-injured spinal cord. Neuroscience 2011 192 588 597
91. Schonberg D. L., Popovich P. G., McTigue D. M., Oligodendrocyte generation is differentially influenced by toll-like receptor (TLR) 2 and TLR4-mediated intraspinal macrophage activation. Journal of Neuropathology and Experimental Neurology 2007 66 12 1124 1135 2-s2.0-37349130280 10.1097/nen.0b013e31815c2530 (Pubitemid 350294662)
92. Triarhou L. C., Herndon R. M., Effect of macrophage inactivation on the neuropathology of lysolecithin-induced demyelination. British Journal of Experimental Pathology 1985 66 3 293 301 2-s2.0-0021886079 (Pubitemid 15032566)
93. Triarhou L. C., Herndon R. M., The effect of dexamethasone on L- α -lysophosphatidyl choline (lysolecithin)-induced demyelination of the rat spinal cord. Archives of Neurology 1986 43 2 121 125 2-s2.0-0022633485 (Pubitemid 16124235)
94. Kotter M. R., Setzu A., Sim F. J., Van Rooijen N., Franklin R. J. M., Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination. Glia 2001 35 3 204 212 2-s2.0-0034846364 10.1002/glia.1085 (Pubitemid 32827763)
95. Kotter M. R., Zhao C., Van Rooijen N., Franklin R. J. M., Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression. Neurobiology of Disease 2005 18 1 166 175 2-s2.0-11844253894 10.1016/j.nbd.2004.09.019 (Pubitemid 40092906)
96. Kotter M. R., Li W. W., Zhao C., Franklin R. J. M., Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation. Journal of Neuroscience 2006 26 1 328 332 2-s2.0-30644476095 10.1523/JNEUROSCI.2615-05.2006 (Pubitemid 43089546)
97. Ruckh J. M., Zhao J. W., Shadrach J. L., van Wijngaarden P., Rao T. N., Wagers A. J., Franklin R. J., Rejuvenation of regeneration in the aging central nervous system. Cell Stem Cell 2012 10 1 96 103
98. Li W. W., Setzu A., Zhao C., Franklin R. J. M., Minocycline-mediated inhibition of microglia activation impairs oligodendrocyte progenitor cell responses and remyelination in a non-immune model of demyelination. Journal of Neuroimmunology 2005 158 1-2 58 66 2-s2.0-10344230955 10.1016/j.jneuroim.2004. 08.011 (Pubitemid 39626071)
99. Yong V. W., Power C., Forsyth P., Edwards D. R., Metalloproteinases in biology and pathology of the nervous system. Nature Reviews Neuroscience 2001 2 7 502 511 2-s2.0-0035405886 10.1038/35081571 (Pubitemid 33676585)
100. Toft-Hansen H., Nuttall R. K., Edwards D. R., Owens T., Key metalloproteinases are expressed by specific cell types in experimental autoimmune encephalomyelitis. Journal of Immunology 2004 173 8 5209 5218 2-s2.0-6344252618 (Pubitemid 39387804)
101. Agrawal S. M., Silva C., Tourtellotte W. W., Yong V. W., EMMPRIN: a novel regulator of leukocyte transmigration into the CNS in multiple sclerosis and experimental autoimmune encephalomyelitis. Journal of Neuroscience 2011 31 2 669 677 2-s2.0-78651515693 10.1523/JNEUROSCI.3659-10.2011
102. Raivich G., Banati R., Brain microglia and blood-derived macrophages: molecular profiles and functional roles in multiple sclerosis and animal models of autoimmune demyelinating disease. Brain Research Reviews 2004 46 3 261 281 2-s2.0-9644310402 10.1016/j.brainresrev.2004.06.006 (Pubitemid 39574328)
103. Murphy A. C., Lalor S. J., Lynch M. A., Mills K. H. G., Infiltration of Th1 and Th17 cells and activation of microglia in the CNS during the course of experimental autoimmune encephalomyelitis. Brain, Behavior, and Immunity 2010 24 4 641 651 2-s2.0-77951879282 10.1016/j.bbi.2010.01.014
104. Peterson J. W., Bö L., Mörk S., Chang A., Ransohoff R. M., Trapp B. D., VCAM-1-positive microglia target oligodendrocytes at the border of multiple sclerosis lesions. Journal of Neuropathology and Experimental Neurology 2002 61 6 539 546 2-s2.0-0036273413 (Pubitemid 34603002)
105. Merrill J. E., Zimmerman R. P., Natural and induced cytotoxicity of oligodendrocytes by microglia is inhibitable by TGF beta. Glia 1991 4 3 327 331 2-s2.0-0026037661
106. Takeuchi H., Mizuno T., Zhang G., Wang J., Kawanokuchi J., Kuno R., Suzumura A., Neuritic beading induced by activated microglia is an early feature of neuronal dysfunction toward neuronal death by inhibition of mitochondrial respiration and axonal transport. Journal of Biological Chemistry 2005 280 11 10444 10454 2-s2.0-15444363122 10.1074/jbc.M413863200 (Pubitemid 40395902)
107. Shijie J., Takeuchi H., Yawata I., Harada Y., Sonobe Y., Doi Y., Liang J., Hua L., Yasuoka S., Zhou Y., Noda M., Kawanokuchi J., Mizuno T., Suzumura A., Blockade of glutamate release from microglia attenuates experimental autoimmune encephalomyelitis in mice. Tohoku Journal of Experimental Medicine 2009 217 2 87 92 2-s2.0-66949120406 10.1620/tjem.217.87
108. Bauer J., Huitinga I., Zhao W., Lassmann H., Hickey W. F., Dijkstra C. D., The role of macrophages, perivascular cells, and microglial cells in the pathogenesis of experimental autoimmune encephalomyelitis. Glia 1995 15 4 437 446 2-s2.0-0029451821
109. Reynolds A., Laurie C., Lee Mosley R., Gendelman H. E., Oxidative stress and the pathogenesis of neurodegenerative disorders. International Review of Neurobiology 2007 82 297 325 2-s2.0-34547307366 10.1016/S0074-7742(07)82016-2
110. Herx L. M., Rivest S., Yong V. W., Central nervous system-initiated inflammation and neurotrophism in trauma: IL-1 β is required for the production of ciliary neurotrophic factor. Journal of Immunology 2000 165 4 2232 2239 2-s2.0-0034663946 (Pubitemid 30643173)
111. Elkabes S., DiCicco-Bloom E. M., Black I. B., Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. Journal of Neuroscience 1996 16 8 2508 2521 2-s2.0-0029972857 (Pubitemid 26122673)
112. Batchelor P. E., Liberatore G. T., Wong J. Y. F., Porritt M. J., Frerichs F., Donnan G. A., Howells D. W., Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Journal of Neuroscience 1999 19 5 1708 1716 2-s2.0-0033104019 (Pubitemid 29094189)
113. Larsen P. H., Wells J. E., Stallcup W. B., Opdenakker G., Yong V. W., Matrix metalloproteinase-9 facilitates remyelination in part by processing the inhibitory NG2 proteoglycan. Journal of Neuroscience 2003 23 35 11127 11135 2-s2.0-0346749451 (Pubitemid 37548948)
114. Wee Yong V., Inflammation in neurological disorders: a help or a hindrance? Neuroscientist 2010 16 4 408 420 2-s2.0-77956302879 10.1177/1073858410371379
115. Johnson K. P., Brooks B. R., Cohen J. A., Ford C. C., Goldstein J., Lisak R. P., Myers L. W., Panitch H. S., Rose J. W., Schiffer R. B., Vollmer T., Weiner L. P., Wolinsky J. S., Bird S. J., Kolson D. L., Gonzalez-Scarano F., Brennan D., Mandler R. N., Rosenberg G. A., Copolymer 1 reduces relapse rate and improves disability in relapsing- remitting multiple sclerosis: results of a phase III multicenter, double- blind, placebo-controlled trial. Neurology 1995 45 7 1268 1276 2-s2.0-0029082566
116. Luessi F., Siffrin V., Zipp F., Neurodegeneration in multiple sclerosis: novel treatment strategies. Expert Review of Neurotherapeutics 2012 12 9 1061 1076
117. Jung S., Siglienti I., Grauer O., Magnus T., Scarlato G., Toyka K., Induction of IL-10 in rat peritoneal macrophages and dendritic cells by glatiramer acetate. Journal of Neuroimmunology 2004 148 1-2 63 73 2-s2.0-1242272715 10.1016/j.jneuroim.2003.11.014 (Pubitemid 38229559)
118. Weber M. S., Starck M., Wagenpfeil S., Meinl E., Hohlfeld R., Farina C., Multiple sclerosis: glatiramer acetate inhibits monocyte reactivity in vitro and in vivo. Brain 2004 127 6 1370 1378 2-s2.0-2942594278 10.1093/brain/awh163 (Pubitemid 38745515)
119. Weber M. S., Prod'homme T., Youssef S., Dunn S. E., Rundle C. D., Lee L., Patarroyo J. C., Stüve O., Sobel R. A., Steinman L., Zamvil S. S., Type II monocytes modulate T cell-mediated central nervous system autoimmune disease. Nature Medicine 2007 13 8 935 943 2-s2.0-34547699396 10.1038/nm1620 (Pubitemid 47222047)
120. Iarlori C., Gambi D., Lugaresi A., Patruno A., Felaco M., Salvatore M., Speranza L., Reale M., Reduction of free radicals in multiple sclerosis: effect of glatiramer acetate (Copaxone). Multiple Sclerosis 2008 14 6 739 748 2-s2.0-48349088568 10.1177/1352458508088918
121. Trojano M., Pellegrini F., Fuiani A., Paolicelli D., Zipoli V., Zimatore G. B., Di Monte E., Portaccio E., Lepore V., Livrea P., Amato M. P., New natural history of interferon- β -treated relapsing multiple sclerosis. Annals of Neurology 2007 61 4 300 306 2-s2.0-34247608145 10.1002/ana.21102 (Pubitemid 46676729)
122. Yong V. W., Differential mechanisms of action of interferon- β and glatiramer acetate in MS. Neurology 2002 59 6 802 808 2-s2.0-0037167526
123. Kieseier B. C., Hartung H. P., Interferon- β and neuroprotection in multiple sclerosis-Facts, hopes and phantasies. Experimental Neurology 2007 203 1 1 4 2-s2.0-33751540077 10.1016/j.expneurol.2006.09.007 (Pubitemid 44830028)
124. Hall G. L., Wing M. G., Compston D. A. S., Scolding N. J., β -interferon regulates the immunomodulatory activity of neonatal rodent microglia. Journal of Neuroimmunology 1997 72 1 11 19 2-s2.0-0031012848 10.1016/S0165-5728(96)00128-2 (Pubitemid 27016149)
125. Kappos L., Radue E. W., O'Connor P., Polman C., Hohlfeld R., Calabresi P., Selmaj K., Agoropoulou C., Leyk M., Zhang-Auberson L., Burtin P., A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. The New England Journal of Medicine 2010 362 5 387 401 2-s2.0-76149093586 10.1056/NEJMoa0909494
126. Rosen H., Goetzl E. J., Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network. Nature Reviews Immunology 2005 5 7 560 570 2-s2.0-21844457949 10.1038/nri1650 (Pubitemid 40961333)
127. Hughes J. E., Srinivasan S., Lynch K. R., Proia R. L., Ferdek P., Hedrick C. C., Sphingosine-1-phosphate induces an antiinflammatory phenotype in macrophages. Circulation Research 2008 102 8 950 958 2-s2.0-42549148380 10.1161/CIRCRESAHA.107.170779 (Pubitemid 351591554)
128. Loma I., Heyman R., Multiple sclerosis: pathogenesis and treatment. Current Neuropharmacology 2011 9 3 409 416 2-s2.0-79960989910 10.2174/157015911796557911
129. Fox E. J., Mechanism of action of mitoxantrone. Neurology 2004 63 12 S15 S18 2-s2.0-10944231932 (Pubitemid 40019273)
130. Kopadze T., Dehmel T., Hartung H. P., Stüve O., Kieseier B. C., Inhibition by mitoxantrone of in vitro migration of immunocompetent cells: a possible mechanism for therapeutic efficacy in the treatment of multiple sclerosis. Archives of Neurology 2006 63 11 1572 1578 2-s2.0-33751010179 10.1001/archneur.63.11.1572 (Pubitemid 44748799)
131. Vollmer T., Stewart T., Baxter N., Mitoxantrone and cytotoxic drugs' mechanisms of action. Neurology 2010 74, supplement 1 S41 S46 2-s2.0-74249113947 10.1212/WNL.0b013e3181c97f5a
132. Watson C. M., Davison A. N., Baker D., O'Neill J. K., Turk J. L., Suppression of demyelination by mitoxantrone. International Journal of Immunopharmacology 1991 13 7 923 930 2-s2.0-0026010353
133. Stoof T. J., Flier J., Sampat S., Nieboer C., Tensen C. P., Boorsma D. M., The antipsoriatic drug dimethylfumarate strongly suppresses chemokine production in human keratinocytes and peripheral blood mononuclear cells. British Journal of Dermatology 2001 144 6 1114 1120 2-s2.0-0035725785 10.1046/j.1365-2133.2001.04220.x (Pubitemid 34204199)
134. Moharregh-Khiabani D., Linker R. A., Gold R., Stangel M., Fumaric acid and its esters: an emerging treatment for multiple sclerosis. Current Neuropharmacology 2009 7 1 60 64 2-s2.0-65949111054 10.2174/157015909787602788
135. Wierinckx A., Brevé J., Mercier D., Schultzberg M., Drukarch B., Van Dam A. M., Detoxication enzyme inducers modify cytokine production in rat mixed glial cells. Journal of Neuroimmunology 2005 166 1-2 132 143 2-s2.0-23044438515 10.1016/j.jneuroim.2005.05.013 (Pubitemid 41074663)
136. Schilling S., Goelz S., Linker R., Luehder F., Gold R., Fumaric acid esters are effective in chronic experimental autoimmune encephalomyelitis and suppress macrophage infiltration. Clinical and Experimental Immunology 2006 145 1 101 107 2-s2.0-33745162188 10.1111/j.1365-2249.2006.03094.x (Pubitemid 43893938)
137. Patani R., Balaratnam M., Vora A., Reynolds R., Remyelination can be extensive in multiple sclerosis despite a long disease course. Neuropathology and Applied Neurobiology 2007 33 3 277 287 2-s2.0-34247862406 10.1111/j.1365-2990.2007.00805.x (Pubitemid 46701044)
138. Kipp M., Victor M., Martino G., Franklin R. J., Endogeneous remyelination: findings in human studies. CNS & Neurological Disorders 2012 11 5 598 609