A possible role for inflammation in mediating apoptosis of oligodendrocytes as induced by the Lyme disease spirochete Borrelia burgdorferi

Journal of Neuroinflammation

Volumn 9, Issue , 2012, Pages

  Ramesh, Geeta ^a   Benge, Shemi ^b   Pahar, Bapi ^a   Philipp, Mario T ^a  

^a TULANE NATIONAL PRIMATE RESEARCH CENTER   (United States)

^b Tulane University   (United States)

Author keywords

Active caspase 3; Apoptosis; Borrelia burgdorferi; CCL2 MCP 1; Dexamethasone; IL 6; IL 8; Lyme neuroborreliosis; Oligodendrocytes

Indexed keywords

CASPASE 3; DEXAMETHASONE; GLIAL FIBRILLARY ACIDIC PROTEIN; INTERLEUKIN 6; INTERLEUKIN 8; MONOCYTE CHEMOTACTIC PROTEIN 1; MYELIN BASIC PROTEIN;

APOPTOSIS; ARTICLE; BORRELIA BURGDORFERI; CELL SURVIVAL; CONCENTRATION RESPONSE; CONTROLLED STUDY; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IN VITRO STUDY; INFLAMMATION; NERVE CELL DIFFERENTIATION; NICK END LABELING; NONHUMAN; OLIGODENDROGLIA; PROTEIN EXPRESSION;

EID: 84859935020     PISSN: None     EISSN: 17422094     Source Type: Journal    
DOI: 10.1186/1742-2094-9-72     Document Type: Article

References (91)

1. Halperin JJ. Nervous system Lyme disease. J R Coll Physicians Edinb 2010, 40:248-255. 10.4997/JRCPE.2010.314, 21127770.
2. Fallon BA, Levin ES, Schweitzer PJ, Hardesty D. Inflammation and central nervous system Lyme disease. Neurobiol Dis 2010, 37:534-541. 10.1016/j.nbd.2009.11.016, 19944760.
3. Reik L, Steere AC, Bartenhagen NH, Shope RE, Malawista SE. Neurologic abnormalities of Lyme disease. Medicine (Baltimore) 1979, 58:281-294.
4. Halperin JJ, Volkman DJ, Wu P. Central nervous system abnormalities in Lyme neuroborreliosis. Neurology 1991, 41:1571-1582. 10.1212/WNL.41.10.1571, 1922798.
5. Neophytides A, Khan S, Louie E. Subacute cerebellitis in Lyme disease. Int J Clin Pract 1997, 51:523-524.
6. Kohler J. Lyme borreliosis: a case of transverse myelitis with syrinx cavity. Neurology 1989, 39:1553-1554.
7. Meurs L, Labeye D, Declercq I, Piéret F, Gille M. Acute transverse myelitis as a main manifestation of early stage II neuroborreliosis in two patients. Eur Neurol 2004, 52:186-188. 10.1159/000081864, 15528925.
8. Koc F, Bozdemir H, Pekoz T, Aksu HS, Ozcan S, Kurdak H. Lyme disease presenting as subacute transverse myelitis. Acta Neurol Belg 2009, 109:326-329.
9. Bigi S, Aebi C, Nauer C, Bigler S, Steinlin M. Acute transverse myelitis in Lyme neuroborreliosis. Infection 2010, 38:413-416. 10.1007/s15010-010-0028-x, 20505978.
10. Componovo F, Meier C. Neuropathy of vasculitic origin in a case of Garin-Boujadoux-Bannwarth syndrome with positive borrelia antibody response. J Neurol 1986, 233:69-72. 10.1007/BF00313849, 3009723.
11. Kindstrand E, Nilsson BY, Hovmark A, Nennesmo I, Pirskanen R, Solders G, Asbrink E. Polyneuropathy in late Lyme borreliosis - a clinical, neurophysiological and morphological description. Acta Neurol Scand 2000, 101:47-52.
12. Lana-Peixoto MA. Multiple sclerosis and positive Lyme serology. Arq Neuropsiquiatr 1994, 52:566-571. 10.1590/S0004-282X1994000400019, 7611954.
13. Brinar VV, Habek M. Rare infections mimicking MS. Clin Neurol Neurosurg 2010, 112:625-628. 10.1016/j.clineuro.2010.04.011, 20439131.
14. Pachner AR. Borrelia burgdorferiin the nervous system: the new " great imitator" . Ann N Y Acad Sci 1988, 539:56-64. 10.1111/j.1749-6632.1988.tb31838.x, 3190104.
15. Hildenbrand P, Craven DE, Jones R, Nemeskal P. Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis. AJNR Am J Neuroradiol 2009, 30:1079-1087. 10.3174/ajnr.A1579, 19346313.
16. Martin R, Gran B, Zhao Y, Markovic-Plese S, Bielekova B, Marques A, Sung MH, Hemmer B, Simon R, McFarland HF, Pinilla C. Molecular mimicry and antigen-specific T cell responses in multiple sclerosis and chronic CNS Lyme disease. J Autoimmun 2001, 16:187-192. 10.1006/jaut.2000.0501, 11334482.
17. Fritzsche M. Chronic Lyme borreliosis at the root of multiple sclerosis: is a cure with antibiotics attainable?. Med Hypotheses 2005, 64:438-448. 10.1016/j.mehy.2004.09.011, 15617845.
18. Halperin JJ. Neuroborreliosis: central nervous system involvement. Semin Neurol 1997, 17:19-24. 10.1055/s-2008-1040908, 9166955.
19. Steinbach JP, Melms A, Skalej M, Dichgans J. Delayed resolution of white matter changes following therapy ofB. burgdorferiencephalitis. Neurology 2005, 64:758-759. 10.1212/01.WNL.0000152048.34121.E1, 15728315.
20. Benach JL. Borrelia burgdorferiin the central nervous system. JAMA 1992, 268:872. author reply 873.
21. Oksi J, Kalimo H, Marttila RJ, Marjamäki M, Sonninen P, Nikoskelainen J, Viljanen MK. Inflammatory brain changes in Lyme borreliosis. A report on three patients and review of literature. Brain 1996, 119:2143-2154. 10.1093/brain/119.6.2143, 9010017.
22. Dryden MS, O'Connell S, Samuel W, Iannotti F. Lyme myelitis mimicking neurological malignancy. Lancet 1996, 348:624.
23. Suchanek G, Kristoferitsch W, Stanek G, Bernheimer H. Anti-myelin antibodies in cerebrospinal fluid and serum of proteins with meningopolyneuritis Garin-Bujadoux-Bannwarth and other neurological diseases. Zentralbl Bakteriol Mikrobiol Hyg A 1986, 263:160-168.
24. Baig S, Olsson T, Höjeberg B, Link H. Cells secreting antibodies to myelin basic protein in cerebrospinal fluid of patients with Lyme neuroborreliosis. Neurology 1991, 41:581-587. 10.1212/WNL.41.4.581, 1707148.
25. Dotevall L, Hagberg L, Karlsson JE, Rosengren LE. Astroglial and neuronal proteins in cerebrospinal fluid as markers of CNS involvement in Lyme neuroborreliosis. Eur J Neurol 1999, 6:169-178. 10.1111/j.1468-1331.1999.tb00010.x, 10053229.
26. Garcia-Moncó JC, Benach JL. Mechanisms of injury in Lyme neuroborreliosis. Semin Neurol 1997, 17:57-62. 10.1055/s-2008-1040914, 9166961.
27. Livengood JA, Gilmore RD. Invasion of human neuronal and glial cells by an infectious strain ofBorrelia burgdorferi. Microbes Infect 2006, 8:2832-2840. 10.1016/j.micinf.2006.08.014, 17045505.
28. García-Moncó JC, Fernández-Villar B, Benach JL. Adherence of the Lyme disease spirochete to glial cells and cells of glial origin. J Infect Dis 1989, 160:497-506. 10.1093/infdis/160.3.497, 2760500.
29. Garcia-Moncó JC, Fernández-Villar B, Szczepanski A, Benach JL. Cytotoxicity ofBorrelia burgdorferifor cultured rat glial cells. J Infect Dis 1991, 163:1362-1366. 10.1093/infdis/163.6.1362, 2037801.
30. Benveniste EN. Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action. Am J Physiol 1992, 263:C1-C16.
31. Merrill JE, Benveniste EN. Cytokines in inflammatory brain lesions: helpful and harmful. Trends Neurosci 1996, 19:331-338. 10.1016/0166-2236(96)10047-3, 8843602.
32. Rothwell NJ, Strijbos PJ. Cytokines in neurodegeneration and repair. Int J Dev Neurosci 1995, 13:179-185. 10.1016/0736-5748(95)00018-C, 7572274.
33. Raivich G, Jones LL, Werner A, Blüthmann H, Doetschmann T, Kreutzberg GW. Molecular signals for glial activation: pro-and anti-inflammatory cytokines in the injured brain. Acta Neurochir Suppl 1999, 73:21-30.
34. Minghetti L. Role of inflammation in neurodegenerative diseases. Curr Opin Neurol 2005, 18:315-321. 10.1097/01.wco.0000169752.54191.97, 15891419.
35. Weller M, Stevens A, Sommer N, Wiethölter H, Dichgans J. Cerebrospinal fluid interleukins, immunoglobulins, and fibronectin in neuroborreliosis. Arch Neurol 1991, 48:837-841. 10.1001/archneur.1991.00530200079022, 1898258.
36. Grusell M, Widhe M, Ekerfelt C. Increased expression of the Th1-inducing cytokines interleukin-12 and interleukin-18 in cerebrospinal fluid but not in sera from patients with Lyme neuroborreliosis. J Neuroimmunol 2002, 131:173-178. 10.1016/S0165-5728(02)00255-2, 12458049.
37. Widhe M, Jarefors S, Ekerfelt C, Vrethem M, Bergstrom S, Forsberg P, Ernerudh J. Borrelia-specific interferon-gamma and interleukin-4 secretion in cerebrospinal fluid and blood during Lyme borreliosis in humans: association with clinical outcome. J Infect Dis 2004, 189:1881-1891. 10.1086/382893, 15122525.
38. Widhe M, Skogman BH, Jarefors S, Eknefelt M, Eneström G, Nordwall M, Ekerfelt C, Croner S, Bergström S, Forsberg P, Ernerudh J. Up-regulation ofBorrelia-specific IL-4 and IFN-gamma-secreting cells in cerebrospinal fluid from children with Lyme neuroborreliosis. Int Immunol 2005, 17:1283-1291. 10.1093/intimm/dxh304, 16176932.
39. Ramesh G, Borda JT, Dufour J, Kaushal D, Ramamoorthy R, Lackner AA, Philipp MT. Interaction of the Lyme disease spirocheteBorrelia burgdorferiwith brain parenchyma elicits inflammatory mediators from glial cells as well as glial and neuronal apoptosis. Am J Pathol 2008, 173:1415-1427. 10.2353/ajpath.2008.080483, 2570132, 18832582.
40. Ramesh G, Borda JT, Gill A, Ribka EP, Morici LA, Mottram P, Martin DS, Jacobs MB, Didier PJ, Philipp MT. Possible role of glial cells in the onset and progression of Lyme neuroborreliosis. J Neuroinflammation 2009, 6:23-38. 10.1186/1742-2094-6-23, 2748066, 19706181.
41. McLaurin J, Trudel GC, Shaw IT, Antel JP, Cashman NR. A human glial hybrid cell line differentially expressing genes subserving oligodendrocyte and astrocyte phenotype. J Neurobiol 1995, 26:283-293. 10.1002/neu.480260212, 7707048.
42. Abraham SM, Lawrence T, Kleiman A, Warden P, Medghalchi M, Tuckermann J, Saklatvala J, Clark AR. Anti-inflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1. J Exp Med 2006, 203:1883-1889. 10.1084/jem.20060336, 2118371, 16880258.
43. Zhou Y, Ling EA, Dheen ST. Dexamethasone suppresses monocyte chemoattractant protein-1 production via mitogen activated protein kinase phosphatase-1 dependent inhibition of Jun N-terminal kinase and p38 mitogen-activated protein kinase in activated microglia. J Neurochem 2007, 102:667-678. 10.1111/j.1471-4159.2007.04535.x, 17403137.
44. Myers TA, Kaushal D, Philipp MT. Microglia are mediators ofBorrelia burgdorferi-induced apoptosis in SH-SY5Y neuronal cells. PLoS Pathog 2009, 5:e1000659. 10.1371/journal.ppat.1000659, 2771360, 19911057.
45. Ramesh G, Alvarez AL, Roberts ED, Dennis VA, Lasater BL, Alvarez X, Philipp MT. Pathogenesis of Lyme neuroborreliosis:Borrelia burgdorferilipoproteins induce both proliferation and apoptosis in rhesus monkey astrocytes. Eur J Immunol 2003, 33:2539-2550. 10.1002/eji.200323872, 12938230.
46. Bernardino AL, Myers TA, Alvarez X, Hasegawa A, Philipp MT. Toll-like receptors: insights into their possible role in the pathogenesis of Lyme neuroborreliosis. Infect Immun 2008, 76:4385-4395. 10.1128/IAI.00394-08, 2546821, 18694963.
47. Stadelmann C, Wegner C, Brück W. Inflammation, demyelination and degeneration-recent insights from MS pathology. Biochim Biophys Acta 2011, 1812:275-282. 10.1016/j.bbadis.2010.07.007, 20637864.
48. Bø L, Vedeler CA, Nyland HI, Trapp BD, Mørk SJ. Subpial demyelination in the cerebral cortex of multiple sclerosis patients. J Neuropathol Exp Neurol 2003, 62:723-732.
49. Schmitz T, Chew LJ. Cytokines and myelination in the central nervous system. Sci World J 2008, 8:1119-1147.
50. Conductier G, Blondeau N, Guyon A, Nahon JL, Rovère C. The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases. J Neuroimmunol 2010, 224:93-100. 10.1016/j.jneuroim.2010.05.010, 20681057.
51. Rollins BJ. Monocyte chemoattractant protein-1: a potential regulator of monocyte recruitment in inflammatory disease. Mol Med Today 1996, 2:198-204. 10.1016/1357-4310(96)88772-7, 8796888.
52. Gerard C, Rollins BJ. Chemokines and disease. Nat Immunol 2001, 2:108-115. 10.1038/84209, 11175802.
53. Simpson JE, Newcombe J, Cuzner ML, Woodroofe MN. Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions. J Neuroimmunol 1998, 84:238-249. 10.1016/S0165-5728(97)00208-7, 9628469.
54. Ransohoff RM, Hamilton TA, Tani M, Stoler MH, Shick HE, Major JA, Estes ML, Thomas DM, Tuohy VK. Astrocyte expression of mRNA encoding cytokines IP-10 and JE/MCP-1 in experimental autoimmune encephalomyelitis. FASEB 1993, 7:592-600.
55. Hinojosa AE, Garcia-Bueno B, Leza JC, Madrigal JL. CCL2/MCP-1 modulation of microglial activation and proliferation. J Neuroinflammation 2011, 8:77-86. 10.1186/1742-2094-8-77, 3146846, 21729288.
56. Grygorczuk S, Zajkowska J, Swierzbińska R, Pancewicz S, Kondrusik M, Hermanowska-Szpakowicz T. Concentration of interferon-inducible T cell chemoattractant and monocyte chemotactic protein-1 in serum and cerebrospinal fluid patients with Lyme borrreliosis. Rocz Akad Med Bialymst 2005, 50:173-178.
57. Perrin FE, Lacroix S, Avilés-Trigueros M, David S. Involvement of monocyte chemoattractant protein-1, macrophage inflammatory protein-1 alpha and interleukin-1 beta in Wallerian degeneration. Brain 2005, 128:854-866. 10.1093/brain/awh407, 15689362.
58. Rotshenker S. Wallerian degeneration: the innate-immune response to traumatic nerve injury. J Neuroinflammation 2011, 8:109. 10.1186/1742-2094-8-109, 3179447, 21878125.
59. Spooren A, Kolmus K, Laureys G, Clinkers R, De Keyser J, Haegeman G, Gerlo S. Brain Interleukin-6, a mental cytokine. Res Rev 2011, 67:157-183.
60. Pizzi M, Sarnico I, Boroni F, Benarese M, Dreano M, Garotta G, Valerio A, Spano P. Prevention of neuron and oligodendrocyte degeneration by interleukin-6 (IL-6) and IL-6 receptor/IL-6 fusion protein in organotypic hippocampal slices. Mol Cell Neuroscienci 2004, 25:301-311.
61. Barres BA, Schmid R, Sendnter M, Raff MC. Multiple extracellular signals are required for long-term oligodendrocyte survival. Development 1993, 118:283-295.
62. Grygorczuk S, Pancewicz S, Zajkowska J, Kondrusik M, Rwierzbińska R, Kermanowska-Szpakowicz T. Concentrations of macrophage inflammatory proteins MIP-1alpha and MIP-1beta and interleukin 8 (IL-8) in Lyme borreliosis. Infection 2004, 32:350-355. 10.1007/s15010-004-3110-4, 15597225.
63. Kossmann T, Stahel PF, Lenzlinger PM, Redl H, Dubs RW, Trentz O, Schlag G, Morganti-Kossmann MC. Interleukin-8 released into the cerebrospinal fluid after brain injury is associated with blood-brain barrier dysfunction and nerve growth factor production. J Cereb Blood Flow Metab 1997, 17:280-289.
64. Dumont RA, Car BD, Voitenok NN, Junker U, Moser B, Zak O, O'Reilly T. Systemic neutralization of interleukin-8 markedly reduces neutrophilic pleocytosis during experimental lipopolysaccharide-induced meningitis in rabbits. Infect Immun 2000, 68:5756-5763. 10.1128/IAI.68.10.5756-5763.2000, 101534, 10992482.
65. Grütter MG. Caspases: key players in programmed cell death. Curr Opin Struct Biol 2000, 10:649-655. 10.1016/S0959-440X(00)00146-9, 11114501.
66. Craighead MW, Tiwari P, Keynes RG, Waters CM. Human oligodendroglial cell line, MO3.13, can be protected from apoptosis using the general caspase inhibitor zVAD-FMK. J Neurosci Res 1999, 57:236-243. 10.1002/(SICI)1097-4547(19990715)57:2<236::AID-JNR9>3.0.CO;2-D, 10398301.
67. Craighead M, Pole J, Waters C. Caspases mediate C2-ceramide-induced apoptosis of the human oligodendroglial cell line, MO3.13. Neurosci Lett 2000, 278:125-128. 10.1016/S0304-3940(99)00866-6, 10653009.
68. Buntinx M, Gielen E, Van Hummelen P, Raus J, Ameloot M, Steels P, Stinissen P. Cytokine-induced cell death in human oligodendroglial cell lines, II: alterations in gene expression induced by interferon-gamma and tumor necrosis factor-alpha. J Neurosci Res 2004, 76:846-861. 10.1002/jnr.20117, 15160396.
69. Hisahara S, Shoji S, Okano H, Miura M. ICE/CED-3 family executes oligodendrocyte apoptosis by tumor necrosis factor. J Neurochem 1997, 69:10-20.
70. Hisahara S, Okano H, Miura M. Caspase-mediated oligodendrocyte cell death in the pathogenesis of autoimmune demyelination. Neurosci Res 2003, 46:387-397. 10.1016/S0168-0102(03)00127-5, 12871760.
71. Selmaj K, Raine CS, Farooq M, Norton WT, Brosnan CF. Cytokine cytotoxicity against oligodendrocytes, Apoptosis induced by lymphotoxin. J Immunol 1991, 147:1522-1529.
72. Schuster N, Bender H, Philippi A, Subramaniam S, Strelau J, Wang Z, Krieglstein K. TGF-beta induces cell death in the oligodendroglial cell line OLI-neu. Glia 2002, 40:95-108. 10.1002/glia.10110, 12237847.
73. Takahashi JL, Giuliani F, Power C, Imai Y, Yong VW. Interleukin-1beta promotes oligodendrocyte death through glutamate excitotoxicity. Ann Neurol 2003, 53:588-595. 10.1002/ana.10519, 12730992.
74. Cai Z, Lin S, Pang Y, Rhodes PG. Brain injury induced by intracerebral injection of interleukin-1beta and tumor necrosis factor-alpha in the neonatal rat. Pediatr Res 2004, 56:377-384. 10.1203/01.PDR.0000134249.92944.14, 15201401.
75. Thirumangalakudi L, Yin L, Rao HV, Grammas P. IL-8 induces expression of matrix metalloproteinases, cell cycle and pro-apoptotic proteins, and cell death in cultured neurons. J Alzheimers Dis 2007, 11:305-311.
76. Brini E, Ruffini F, Bergami A, Brambilla E, Dati G, Greco B, Cirillo R, Proudfoot AE, Comi G, Furlan R, Zaratin P, Martino G. Administration of a monomeric CCL2 variant to EAE mice inhibits inflammatory cell recruitment and protects from demyelination and axonal loss. J Neuroimmunol 2009, 209:33-39. 10.1016/j.jneuroim.2009.01.022, 19232440.
77. Nordberg M, Forsberg P, Johansson A, Nyman D, Jansson C, Ernerudh J, Ekerfelt C. Cytotoxic mechanisms may play a role in the local immune response in the central nervous system in neuroborreliosis. J Neuroimmunol 2011, 232:186-193. 10.1016/j.jneuroim.2010.09.028, 21056912.
78. Ekerfelt C, Jarefors S, Tynngård N, Hedlund M, Sander B, Bergström S, Forsberg P, Ernerudh J. Phenotypes indicating cytolytic properties of Borrelia-specific interferon-gamma secreting cells in chronic Lyme neuroborreliosis. J Neuroimmunol 2003, 145:115-126. 10.1016/j.jneuroim.2003.08.037, 14644037.
79. Bruin KF, Hommes DW, Jansen J, Tytgat GN, Wouter Ten Cate J, van Deventer SJ. Modulation of cytokine release from human monocytes by drugs used in the therapy of inflammatory bowel diseases. Eur J Gastroenterol Hepatol 1995, 7:791-795.
80. Harkness KA, Sussman JD, Davies-Jones GA, Greenwood J, Woodroofe MN. Cytokine regulation of MCP-1 expression in brain and retinal microvascular endothelial cells. J Neuroimmunol 2003, 142:1-9. 10.1016/S0165-5728(03)00251-0, 14512159.
81. Loetscher P, Dewald B, Baggiolini M, Seitz M. Monocyte chemoattractant protein 1 and interleukin 8 production by rheumatoid synoviocytes, Effects of anti-rheumatic drugs. Cytokine 1994, 6:162-170. 10.1016/1043-4666(94)90038-8, 8031999.
82. Massengo SA, Bonnet F, Braun C, Vital A, Beylot J, Bastard J. Severe neuroborreliosis: the benefit of prolonged high dose combination of antimicrobial agents with steroids - an illustrative case. Diagn Microbiol Infect Dis 2005, 51:127-130. 10.1016/j.diagmicrobio.2004.04.022, 15698718.
83. Dong C, Davis RJ, Flavell RA. MAP kinases in the immune response. Annu Rev Immunol 2002, 20:55-72. 10.1146/annurev.immunol.20.091301.131133, 11861597.
84. Wang X, Liu Y. Regulation of innate immune response by MAP kinase phosphatase-1. Cell Signal 2007, 19:1372-1382. 10.1016/j.cellsig.2007.03.013, 2203964, 17512700.
85. Tibbles LA, Woodgett JR. The stress-activated protein kinase pathways. Cell Mol Life Sci 1999, 55:1230-1254. 10.1007/s000180050369, 10487205.
86. Ramesh G, Philipp MT. Pathogenesis of Lyme neuroborreliosis: mitogen-activated protein kinases Erk 1, Erk 2 and p38 in the response of astrocytes toBorrelia burgdorferilipoproteins. Neurosci Lett 2005, 384:112-116. 10.1016/j.neulet.2005.04.069, 15893422.
87. Jakovcevski I, Filipovic R, Mo Z, Rakic S, Zecevic N. Oligodendrocyte development and the onset of myelination in the human fetal brain. Front Neuroanat 2009, 3:5-15. 2694674, 19521542.
88. Brück W. The pathology of multiple sclerosis is the result of focal inflammatory demyelination with axonal damage. J Neurol 2005, Suppl 5:v3-v9.
89. Butts BD, Houde C, Mehmet H. Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease. Cell Death Differ 2008, 15:1178-1186. 10.1038/cdd.2008.70, 18483490.
90. Matute C, Perez-Cerda F. Multiple sclerosis: novel perspectives on newly forming lesions. Trends Neurosci 2005, 28:173-175. 10.1016/j.tins.2005.01.006, 15808350.
91. Bradl M, Lassmann H. Oligodendrocytes: biology and pathology. Acta Neuropathol 2010, 119:37-53.