The involvement of mitochondria in the pathogenesis of multiple sclerosis

Journal of Neuroimmunology

Volumn 188, Issue 1-2, 2007, Pages 1-12

  Kalman, Bernadette ^a   Laitinen, Karen ^b   Komoly, Samuel ^c  

^a SUNY UPSTATE MEDICAL UNIVERSITY   (United States)

^b SYRACUSE VA MEDICAL CENTER   (United States)

^c UNIVERSITY OF PÉCS   (Hungary)

Author keywords

Apoptosis; Inflammation; Mitochondrion; Multiple sclerosis; Neurodegeneration

Indexed keywords

CASPASE; FAS ANTIGEN; GAMMA INTERFERON; LYMPHOTOXIN; MITOCHONDRIAL DNA; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND;

ALLERGIC ENCEPHALOMYELITIS; ASTROCYTOSIS; ATHEROSCLEROTIC PLAQUE; CELL DEATH; CELL SURVIVAL; DEMYELINATION; DISEASE ASSOCIATION; ENERGY METABOLISM; ENZYME ACTIVATION; GRAY MATTER; HOMEOSTASIS; HUMAN; IMMUNOREGULATION; INFLAMMATION; MITOCHONDRION; MOUSE STRAIN; MULTIPLE SCLEROSIS; MURINE ENCEPHALOMYELITIS VIRUS; NERVE DEGENERATION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OLIGODENDROGLIA; OXIDATIVE STRESS; PATHOGENESIS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; WHITE MATTER;

ANIMALS; HUMANS; MITOCHONDRIA; MODELS, BIOLOGICAL; MULTIPLE SCLEROSIS;

EID: 34447640526     PISSN: 01655728     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jneuroim.2007.03.020     Document Type: Review

References (102)

1. Aboul-Enein F., and Lassmann H. Mitochondrial damage and histotoxic hypoxia: a pathway of tissue injury in inflammatory brain disease?. Acta Neuropathol. (Berl) 109 (2005) 49-55
2. Aktas O., Prozorovski T., and Zipp F. Death ligands and autoimmune demyelination. Neurosci. 2 (2006) 305-316
3. Anderson S., Bankier A.T., Barrell B.G., de Bruijn M.H., Coulson A.R., Drouin J., Eperon I.C., Nielich D.P., Roe B.A., Sanger F., Schreier P.H., Smith A.J., Staden R., and Young I.G. Sequence and organization of the human mitochondrial genome. Nature 290 (1981) 457-465
4. Andrews H.E., Nichols P.P., Bates D., and Turnbull D.M. Mitochondrial dysfunction plays a key role in progressive axonal loss in multiple sclerosis. Med. Hypotheses 64 (2005) 669-677
5. Andrews H., White K., Thomson C., Edgar J., Bates D., Griffiths I., Turnbull D., and Nichols P. Increased axonal mitochondrial activity as an adaptation to myelin deficiency in the Shiverer mouse. J. Neurosci. Res. 83 (2006) 1533-1539
6. Arbour N., Rastikerdar E., McCrea E., Lapierre Y., Dorr J., Bar-Or A., and Antel J.P. Upregulation of TRAIL expression on human T lymphocytes by interferon beta and glatiramer acetate. Mult. Scler. 11 (2005) 652-657
7. Bagnato F., Jeffries N., Richert N.D., Stone R.D., Ohayon J.M., McFarland H.F., and Frank J.A. Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain 126 Pt 8 (2003) 1782-1789
8. Bakshi R., Benedict R.H., Bermel R.A., Caruthers S.D., Puli S.R., Tjoa C.W., Fabiano A.J., and Jacobs L. T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study. Arch. Neurol. 59 (2002) 62-68
9. Bakshi R., Dandamudi V.S.R., Neema M., De C., and Bermel R.A. Measurement of brain and spinal cord atrophy by magnetic resonance imaging as a tool to monitor multiple sclerosis. J. Neuroimaging 15 Suppl 4 (2005) 30S-45S
10. Balbanov R., Strand K., Kemper A., Lee J.Y., and Popko B. Suppressor of cytokine signaling 1 expression protects oligodendrocytes from the deleterious effects of interferon-gamma. J. Neurosci. 26 (2006) 5143-5152
11. Barnett M.H., and Prineas J.W. Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann. Neurol. 55 (2004) 458-468
12. Barnett M.H., and Sutton I. The pathology of multiple sclerosis: a paradigm shift. Curr. Opin. Neurol. 19 (2006) 242-247
13. Bender A., Krishnan K.J., Morris C.M., Taylor G.A., Reeve A.K., Perry R.H., Jaros E., Hersheson J.S., Betts J., Klopstock T., Taylor R.W., and Turnbull D.M. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat. Genet. 38 (2006) 515-517
14. Bermel R.A., Puli S.R., Rudick R.A., Weinstock-Guttman B., Fisher E., Munschauer III F.E., and Bakshi R. Prediction of longitudinal brain atrophy in multiple sclerosis by gray matter magnetic resonance imaging T2 hypointensity. Arch. Neurol. 62 (2005) 1371-1376
15. Bielekova B., Kadom N., Fisher E., Jeffries N., Ohayon J., Richert N., Howard T., Bash C.N., Frank J.A., Stone L., Martin R., Cutter G., and McFarland H.F. MRI as a marker for disease heterogeneity in multiple sclerosis. Neurology 65 (2005) 1071-1076
16. Bjartmar C., and Trapp B.D. Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences. Curr. Opin. Neurol. 14 (2001) 271-278
17. Bonettie B., and Raine C.S. Multiple sclerosis: oligodendrocytes display cell death-related molecules in situ but do not undergo apoptosis. Ann. Neurol. 42 (1997) 74-78
18. Brass S.D., Benedict R.H., Weinstock-Guttman B., Munschauer F., and Bakshi R. Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis. Mult. Scler. 12 (2006) 437-444
19. Cammer W. The neurotoxicant, cuprizone, retards the differentiation of oligodendrocytes in vitro. J. Neurol. Sci. 168 (1999) 116-120
20. Campuzano V., Montermini L., Molto M.D., Pianese L., Cossee M., Cavalcanti F., Monros E., Rodius F., Duclos F., Monticelli A., Zara F., Canizares J., Koutnikova H., Bidichandani S.I., Gellera C., Brice A., Trouillas P., De Michele G., Filla A., De Frutos R., Palau F., Patel P.I., Di Donato S., Mandel J.L., Cocozza S., Koenig M., and Pandolfo M. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271 (1996) 1423-1427
21. Comi G., Filippi M., Wolinsky J.S., and the European/Canadian Glatiramer acetate Study Group. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging-measured disease activity and burden in patients with relapsing multiple sclerosis. Ann. Neurol. 49 (2001) 290-297
22. Cross A.H., Manning P.T., Stern M.K., and Misko T.P. Evidence for the production of peroxynitrite in inflammatory CNS demyelination. J. Neuroimmunol. 80 (1997) 121-130
23. Craner M.J., Newcombe J., Black J.A., Hartle C., Cuzner M.L., and Waxman S.G. Molecular changes in neurons in multiple sclerosis: altered axonal expression of Nav1.2 and Nav1.6 sodium channels and Na+/Ca2+ exchanger. Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 8168-8173
24. Cudrici C., Niculescu T., Niculescu F., Shin M.L., and Rus H. Oligodendrocyte cell death in pathogenesis of multiple sclerosis: protection of oligodendrocytes from apoptosis by complement. J. Rehabil. Res. Dev. 43 (2006) 123-132
25. Degterev A., Boyce M., and Yuan J. A decade of caspases. Oncogene 22 (2003) 8543-8567
26. DiMauro S., and Hirano M. Mitochondrial encephalomyopathies: an update. Neuromuscul. Disord. 15 4 (2005) 276-286
27. Dowling P., Husar W., Menonna J., Donnenfeld H., Cook S., and Sidhu M. Cell death and birth in multiple sclerosis brain. J. Neurol. Sci. 149 (1997) 1-11
28. Druzhyna N.M., Musiyenko S.I., Wilson G.L., and LeDoux S.P. Cytokines induce nitric oxide-mediated mtDNA damage and apoptosis in oligodendrocytes. Protective role of targeting 8-oxoguanine glycosylase to mitochondria. J. Biol. Chem. 280 (2005) 21673-21679
29. D'Souza S.D., Bonetti B., Balasingam V., Cashman N.R., Barker P.A., Troutt A.B., Raine C.S., and Antel J.P. Multiple sclerosis - Fas signaling in oligodendrocyte cell death. J. Exp. Med. 184 (1996) 2361-2370
30. Dutta R., McDonough J., Yin X., Peterson J., Chang A., Torres T., Gudz T., Macklin W.B., Lewis D.A., Fox R.J., Rudick R., Mirnics K., and Trapp B.D. Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann. Neurol. 59 (2006) 478-489
31. Fas S.C., Fritzsching B., Suri-Payer E., and Krammer P.H. Death receptor signaling and its function in the immune system. Curr. Dir. Autoimmun. 9 (2006) 1-17
32. Filippi M., Rocca M.A., Martino G., Horsfield M.A., and Comi G. Magnetization transfer changes in the normal appearing white matter precede the appearance of enhancing lesions in patients with multiple sclerosis. Ann. Neurol. 43 (1998) 809-814
33. Filippi M., Rovaris M., Iannucci G., Mennea S., Sormani M.P., and Comi G. Whole brain volume changes in patients with progressive MS treated with cladribine. Neurology 55 (2000) 1714-1718
34. Geurts J.J., Pouwels P.J., Uitdehaag B.M., Polman C.H., Barkhof F., and Castelijns J.A. Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging. Radiology 236 (2005) 254-260
35. Gonzalez-Toledo E., Kelley R.E., and Minagar A. Role of magnetic resonance spectroscopy in diagnosis and management of multiple sclerosis. Neurol. Res. 28 (2006) 280-283
36. Graumann U., Reynolds R., Steck A.J., and Schaeren-Weimers N. Molecular changes in normal appearing white matter in multiple sclerosis are characteristic of neuroprotective mechanisms against hypoxic insult. Brain Pathol. 13 (2003) 554-573
37. Gregersen J.W., Kranc K.R., Ke X., Svendsen P., Madsen L.C., Thomsen A.R., Cardon L.R., Bell J.I., and Fugger L. Functional epistasis on a common MHC haplotype associated with multiple sclerosis. Nature 443 (2006) 574-577
38. Griffiths I., Klugmann M., Anderson T., Yool D., Thomson C., Schwab M.H., Schneider A., Zimmermann F., McCulloh M., Nadon N., and Nave K.A. Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science 280 (1998) 1610-1613
39. Heales S.J., Bolanos J.P., Stewart V.C., Brookes P.S., Land J.M., and Clark J.B. Nitric oxide, mitochondria and neurological disease. Biochim. Biophys. Acta 1410 (1999) 215-228
40. Hovelmeyer N., Hao Z., Kranidioti K., Kassiotis G., Buch T., Frommer F., von Hoch L., Kramer D., Minichiello L., Kollias G., Lassmann H., and Waisman A. Apoptosis of oligodendrocytes via Fas and TNF-R1 is a key event in the induction of experimental autoimmune encephalomyelitis. J. Immunol. 175 (2005) 5875-5884
41. Inglese M., Mancardi G.L., Pagani E., Rocca M.A., Murialdo A., Saccardi R., Comi G., Filippi M., and Italian GITMO-NEURO Group on Autologous Hematopoietic Stem Cell Transplantation. Brain tissue loss occurs after suppression of enhancement in patients with multiple sclerosis treated with autologous haematopoietic stem cell transplantation. J. Neurol. Neurosurg. Psychiatry 75 (2004) 643-644
42. Inglese M., Benedetti B., and Filippi M. The relationship between MRI measures of inflammation and neurodegeneration in multiple sclerosis. J. Neurol. Sci. 233 (2005) 15-19
43. Jurewicz A., Matysiak M., Tybor K., and Selmaj K. TNF-induced death of adult human oligodendrocytes is mediated by c-jun NH2-terminal kinase-3. Brain 125 (2003) 1358-1370
44. Jurewicz A., Matysiak M., Tybor K., Kilianek L., Raine C.S., and Selmaj K. Tumor necrosis factor-induced death of adult human oligodendrocytes is mediated by apoptosis inducing factor. Brain 125 (2005) 2675-2688
45. Jurewicz A., Matysiak M., Andrzejak S., and Selmaj K. TRAIL-induced death of human adult oligodendrocytes is mediated by JNK pathway. Glia 53 (2006) 158-166
46. Kalman B. Role of mitochondria in MS. Current Neurology and Neuroscience Report. Section: Demyelinating Disorders vol. 6 (2006) 244-252
47. Kalman B., and Leist T.P. A mitochondrial component of neurodegeneration in multiple sclerosis. NeuroMol. Med. 3 (2003) 147-157
48. Kalman K., Lublin F.D., and Alder H. Characterization of the mitochondrial DNA in multiple sclerosis. J. Neurol. Sci. 140 (1996) 75-89
49. Kalman B., Li S., Chatterjee D., O'Connor J., Voehl M., Brown M.D., and Alder H. Large scale screening of the mitochondrial DNA reveals no pathogenic or polymorphic mutations but a haplotype associated with multiple sclerosis in Caucasians. Acta Neurol. Scand. 99 (1999) 16-25
50. Kalman B., Albert R.H., and Leist T.P. Genetics of multiple sclerosis: determinants of autoimmunity and neurodegeneration. Autoimmunity 35 (2002) 225-234
51. Karthikeyan G., Santos J.H., Graziewicz M.A., Copeland W.C., Isaya G., Van Houten B., and Resnick M.A. Reduction in frataxin causes progressive accumulation of mitochondrial damage. Hum. Mol. Genet. 12 (2003) 3331-3342
52. Kermode A.G., Thompson A.J., Tofts P., MacManus D.G., Kendall B.E., Kingsley D.P., Moseley I.F., Rudge P., and McDonald W.I. Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenic and clinical implications. Brain 113 (1990) 1477-1499
53. Kidd D., Barkhof F., McConnell R., Algra P.R., Allen I.V., and Revesz T. Cortical lesions in multiple sclerosis. Brain 122 (1999) 17-26
54. Komoly S., Hudson L.D., Webster H.d.F., and Bondy C.A. Insulin-like growth factor I expression is induced in astrocytes during experimental demyelination. Proc. Natl. Acad. Sci. U. S. A. 89 (1992) 1894-1898
55. Kraytsberg Y., Kudryavtseva E., McKee A.C., Geula C., Kowall N.W., and Khrapko K. Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat. Genet. 38 (2006) 518-520
56. Kumleh H.H., Riazi G.H., Houshmand M., Sanati M.H., Gharagozli K., and Shafa M. Complex I deficiency in Persian multiple sclerosis patients. J. Neurol. Sci. 15 (2006) 65-69
57. Kutzelnigg A., Lucchinetti C.F., Stadelmann C., Bruck W., Rauschka H., Bergmann M., Schmidbauer M., Parisi J.E., and Lassmann H. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128 (2005) 2705-2712
58. Lassmann H. Multiple sclerosis pathology: evolution of pathogenic concepts. Brain Pathol. 15 (2005) 217-222
59. LeVine S.M. Iron deposits in multiple sclerosis and Alzheimer's disease brains. Brain Res. 760 (1997) 298-303
60. Li D.K.B., Paty D.W., and The UBC MS/MRI Analysis Research Group and the PRISM Study Group. Magnetic resonance imaging results of the PRISM trial: a randomized, double-blind, placebo-controlled study of interferon-beta 1a in relapsing-remitting multiple sclerosis. Ann. Neurol. 46 (1999) 197-206
61. Lu F., Selak M., O'Connor J., Croul S., Butunoi C., and Kalman B. Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in lesions of multiple sclerosis. J. Neurol. Sci. 177 (2000) 95-103
62. Lublin F.D., and Reingold S.C. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46 (1996) 907-911
63. Lucchinetti C., Bruck W., Parisi J., Scheithauer B., Rodriguez M., and Lassmann H. Heterogeneity of multiple sclerosis lesions: implication for the pathogenesis of demyelination. Ann. Neurol. 47 (2000) 707-717
64. Mann-Chandler M.N., Kashyap M., Wright H.V., Norozian F., Barnstein B.O., Gingras S., Parganas E., and Ryan J.J. IFN-gamma induces apoptosis in developing mast cells. J. Immunol. 175 (2005) 3000-3005
65. Martinou J.C., and Green D.R. Breaking the mitochondrial barrier. Nat. Rev., Mol. Cell Biol. 2 (2001) 63-67
66. Mehindate K., Sahlas D.J., Frankel D., Mawal Y., Liberman A., Corcos J., Dion S., and Schipper H.M. Proinflammatory cytokines promote glial heme oxygenase-1 expression and mitochondrial iron deposition: implications for multiple sclerosis. J. Neurochem. 77 (2001) 1386-1395
67. Naismith R.T., and Cross A.H. Multiple sclerosis and black holes. Connecting pixels. Arch. Neurol. 62 (2005) 1666-1668
68. Okuda Y., Apatoff B.R., and Posnett D.N. Apoptosis of T cells in peripheral blood and cerebrospinal fluid is associated with disease activity of multiple sclerosis. J. Neuroimmunol. 171 (2006) 163-170
69. Paolillo A., Pozzilli C., Giugni E., Tomassini V., Gasperini C., Fiorelli M., Mainero C., Horsfield M., Galgani S., Bastianello S., and Buttinelli C. A 6-year clinical and MRI follow-up study of patients with relapsing-remitting multiple sclerosis treated with Interferon-beta. Eur. J. Neurol. 9 (2002) 645-655
70. Perier O., and Gregoire A. Electron microscopic features of multiple sclerosis lesions. Brain 88 (1965) 937-952
71. Peterson J.W., Bo L., Mork S., Chang A., and Trapp B.D. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann. Neurol. 50 (2001) 389-400
72. Peterson J.W., Bo L., Mork S., Chang A., Ransohoff R.M., and Trapp B.D. VCAM-1-positive microglia target oligodendrocytes at the border of multiple sclerosis lesions. J. Neuropathol. Exp. Neurol. 61 (2002) 539-546
73. Pirko I., Lucchinetti C.F., Sriram S., and Bakshi R. Gray matter involvement in multiple sclerosis. Neurology 68 (2007) 634-642
74. Polman C.H., O'Connor P.W., Havrdova E., Hutchinson M., Kappos L., Miller D.H., Phillips J.T., Lublin F.D., Giovannoni G., Wajgt A., Toal M., Lynn F., Panzara M.A., Sandrock A.W., and AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. 354 (2006) 899-910
75. Preito A., Diaz D., Barcenilla H., Castrillo C., Monserrat J., Merino A.G., Alvarez-Mon M., and GENIO II-group. Increased spontaneous ex vivo apoptosis and subset alteration in peripheral blood T cells from patients with multiple sclerosis. J. Clin. Immunol. 26 (2006) 101-112
76. Prineas J.W., Barnard R.O., Kwon E.E., Sharer L.R., and Cho E.S. Multiple sclerosis: remyelination of nascent lesions. Ann. Neurol. 33 (1993) 137-151
77. Qi X., Lewin A.S., Sun L., Hauswirth W.W., and Guy J. Mitochondrial protein nitration primes neurodegeneration in experimental autoimmune encephalomyelitis. J. Biol. Chem. 281 (2006) 31950-31962
78. Qi X., Lewin A.S., Sun L., Hauswirth W.W., and Guy J. Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis. Invest. Ophthalmol. Visual Sci. 48 (2007) 681-691
79. Richert N.D., Howard T., Frank J.A., Stone R., Ostuni J., Ohayon J., Bash C., and McFarland H.F. Relationship between inflammatory lesions and cerebral atrophy in multiple sclerosis. Neurology 66 (2006) 551-556
80. Rudick R.A., Goodman A., Herndon R.M., and Panitch H.S. Selecting relapsing remitting multiple sclerosis patients for treatment: the case for early treatment. J. Neuroimmunol. 98 (1999) 22-28
81. Rudick R.A., Stuart W.H., Calabresi P.A., Confavreux C., Galetta S.L., Radue E.W., Lublin F.D., Weinstock-Guttman B., Wynn D.R., Lynn F., Panzara M.A., Sandrock A.W., and SENTINEL Investigators. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N. Engl. J. Med. 354 (2006) 911-923
82. Sabelko-Downes K.A., Russel J.H., and Cross A.H. Role of Fas-FasL interactions in the pathogenesis and regulation of autoimmune demyelinating disease. J. Neuroimmunol. 100 (1999) 42-52
83. Sathornsumetee S., McGavern D.B., Ure D.R., and Rodriguez M. Quantitative ultrastructural analysis of a single spinal cord demyelination lesion predicts total lesion load, axonal loss, and neurological dysfunction in a murine model of multiple sclerosis. Am. J. Pathol. 157 (2000) 1365-1376
84. Schapira A.H. Mitochondrial disorders. Curr. Opin. Neurol. 13 (2000) 527-532
85. Schipper H.M. Heme oxygenase-1: transducer of pathological brain iron sequestration under oxidative stress. Ann. N. Y. Acad. Sci. 1012 (2004) 84-93
86. Selmaj K., Cross A.H., Farooq M., Brosnan C.F., and Raine C.S. Non-specific oligodendrocyte cytotoxicity mediated by soluble products of activated T cell lines. J. Neuroimmunol. 35 (1991) 261-271
87. Stadelmann C., Ludwin S., Tabira T., Guseo A., Lucchinetti C.F., Leel-Ossy L., Ordinario A.T., Bruck W., and Lassmann H. Tissue preconditioning may explain concentric lesions in Balo's type of multiple sclerosis. Brain 128 (2005) 979-987
88. Suzuki K. Giant hepatic mitochondria: production of mice fed with cuprizone. Science 163 (1969) 81-82
89. Takeuchi H., Wang J., Kawanokuchi J., Mitsuma N., Mizuno T., and Suzumura A. Interferon-gamma induces microglial-activation-induced cell death: a hypothetical mechanism of relapse and remission in multiple sclerosis. Neurobiol. Dis. 22 (2006) 33-39
90. Tandler B., and Hoppel C. Division of giant mitochondria during recovery from cuprizone intoxication. J. Cell Biol. 56 (1973) 266-272
91. Taylor R.W., and Turnbull D.M. Mitochondrial DNA mutations in human disease. Nat. Rev., Genet. 6 (2005) 389-402
92. Thompson A.J., Kermode A.G., Wicks D., MacManus D.G., Kendall B.E., Kingsley D.P., and McDonald W.I. Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann. Neurol. 29 (1991) 53-62
93. Trapp B.D., Peterson J., Ransohoff R.M., Rudick R., Mork S., and Bo L. Axonal transection in the lesions of multiple sclerosis. N. Engl. J. Med. 338 (1998) 278-285
94. Trapp B.D., Bo L., Mork S., and Chang A. Pathogenesis of tissue injury in MS lesions. J. Neuroimmunol. 98 (1999) 49-56
95. Vanderlocht J., Hellings N., Hendricks J.J., Vanderabeele F., Moreels M., Buntinx M., Hoekstra D., Antel J.P., and Stinissen P. Leukemia inhibitory factor is produced by myelin-reactive T cells from multiple sclerosis patients and protects against tumor necrosis factor-alpha-induced oligodendrocyte apoptosis. J. Neurosci. Res. 83 (2006) 763-764
96. Vercellino M., Plano F., Votta B., Mutani R., Giordana M.T., and Cavalla P. Grey matter pathology in multiple sclerosis. J. Neuropathol. Exp. Neurol. 64 (2005) 1101-1107
97. Vladimirova O., O'Connor J., Cahill A., Alder H., and Kalman B. Oxidative damage to DNA in plaques of MS brains. Mult. Scler. 4 (1998) 413-418
98. Vladimirova O., Lu F.M., Shawver L., and Kalman B. The activation of protein kinase C induces higher production of reactive oxygen species by mononuclear cells in patients with multiple sclerosis than in controls. Inflamm. Res. 48 (1999) 412-416
99. Vyshkina T., Banisor I., Yao Shugart Y., Leist T.P., and Kalman B. Genetic variants of Complex I in multiple sclerosis. J. Neurol. Sci. 228 (2005) 55-64
100. Wegener C., Esiri M.M., Chance S.A., Palace J., and Matthews P.M. Neocortical neuronal, synaptic, and glial loss in multiple sclerosis. Neurology 67 (2006) 960-967
101. Zamzami N., and Kroemer G. The mitochondrion in apoptosis: how Pandora's box opens. Nat. Rev., Mol. Cell Biol. 2 (2001) 67-71
102. Zhang X., Haaf M., Todorich B., Grosstephan E., Schieremberg H., Surguladze N., and Connor J.R. Cytokine toxicity to oligodendrocyte precursors is mediated by iron. Glia 52 (2005) 199-208