Skip to main content

Advertisement

Log in

Oxidative Stress and Neurobiology of Demyelination

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Despite a large amount of research which aims at defining the pathophysiology of human demyelination (i.e., multiple sclerosis), etiological bases of disease have been unknown so far. The point of intersection of all assumed etiological factors, which are mainly based upon immunological cascades, is neuroinflammation. The precise definition of the place and role of all pathogenetic factors in the occurrence and development of the disease is of crucial importance for understanding the clinical nature and for finding more effective therapeutic options. There are few studies whose results give more precise data about the role and the importance of other factors in neuroinflammation, besides immunological ones, with regard to clinical and paraclinical correlates of the disease. The review integrates results found in previously performed studies which have evaluated oxidative stress participation in early and late neuroinflammation. The largest number of studies indicates that the use of antioxidants affects the change of neuroinflammation course under experimental conditions, which is reflected in the reduction of the severity and the total reversibility in clinical presentation of the disease, the faster achieving of remission, and the delayed and slow course of neuroinflammation. Therapies based on the knowledge of redox biology targeting free radical generation hold great promise in modulation of the neuroinflammation and its clinical presentations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ames AI (2000) CNS energy metabolism as related to function. Brain Res Rev 34:42–68

    Article  CAS  PubMed  Google Scholar 

  2. Galea I, Bechmann I, Perry VH (2007) What is immune privilege (not)? Trends Immunol 28:12–18

    Article  CAS  PubMed  Google Scholar 

  3. Abbott NJ, Ronnback L, Hansson E (2006) Astrocyte–endothelial interactions at the blood–brain barrier. Nat Rev Neurosci 7:41–53

    Article  CAS  PubMed  Google Scholar 

  4. Bailey SL, Carpentier PA, McMahon EJ, Begolka WS, Miller SD (2006) Innate and adaptive immune responses of the central nervous system. Crit Rev Immunol 26:149–188

    Article  CAS  PubMed  Google Scholar 

  5. Owens T, Bechmann I, Engelhardt B (2008) Perivascular spaces and the two steps to neuroinflammation. J Neuropathol Exp Neurol 67:1113–1121

    Article  PubMed  Google Scholar 

  6. Chan WY, Kohsaka S, Rezaie P (2007) The origin and cell lineage of microglia: new concepts. Brain Res Rev 53:344–354

    Article  CAS  PubMed  Google Scholar 

  7. Block ML, Hong JS (2005) Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 76(2):77–98

    Article  CAS  PubMed  Google Scholar 

  8. Mrak RE, Griffin WS (2005) Glia and their cytokines in progression of neurodegeneration. Neurobiol Aging 26(3):349–354

    Article  CAS  PubMed  Google Scholar 

  9. Ladeby R, Wirenfeldt M, Garcia-Ovejero D, Fenger C, Dissing-Olesen L, Dalmau I, Finsen B (2005) Microglial cell population dynamics in the injured adult central nervous system. Brain Res Rev 48:196–206

    Article  CAS  PubMed  Google Scholar 

  10. Dheen ST, Kaur C, Ling EA (2007) Microglial activation and its implications in the brain diseases. Curr Med Chem 14:1189–1197

    Article  CAS  PubMed  Google Scholar 

  11. Fabriek BO, Van Haastert ES, Galea I, Polfliet MM, Dopp ED, Van Den Heuvel MM, Van Den Berg TK, De Groot CJ, Van DV, Dijkstra CD (2005) CD163 positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation. Glia 51:297–305

    Article  PubMed  Google Scholar 

  12. Rivest S (2009) Regulation of innate immune responses in the brain. Nat Rev Immunol 9(6):429–439

    Article  CAS  PubMed  Google Scholar 

  13. Kivisakk P, Imitola J, Rasmussen S, Elyaman W, Zhu B, Ransohoff RM, Khoury SJ (2009) Localizing central nervous system immune surveillance: meningeal antigen-presenting cells activate T cells during experimental autoimmune encephalomyelitis. Ann Neurol 65:457–469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Fetler L, Amigorena S, Neuroscience (2005) Brain under surveillance: the microglia patrol. Science 309:392–393

    Article  CAS  PubMed  Google Scholar 

  15. 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(5):1175–1189

    Article  PubMed  PubMed Central  Google Scholar 

  16. Schnell L, Fearn S, Klassen H, Schwab ME, Perry VH (1999) Acute inflammatory responses to mechanical lesions in the CNS: differences between brain and spinal cord. Eur J Neurosci 11:3648–3658

    Article  CAS  PubMed  Google Scholar 

  17. Ponomarev ED, Shriver LP, Maresz K, Dittel BN (2005) Microglial cell activation and proliferation precedes the onset of CNS autoimmunity. J Neurosci Res 81:374–389

    Article  CAS  PubMed  Google Scholar 

  18. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG (2000) Multiple sclerosis. N Engl J Med 343:938–952

    Article  CAS  PubMed  Google Scholar 

  19. Hafler DA (2004) Multiple sclerosis. J Clin Invest 113:788–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rizvi SI, Maurya PK (2007) Alterations in antioxidant enzymes during aging in humans. Mol Biotechnol 37:58–61

    Article  CAS  PubMed  Google Scholar 

  21. van Horssen J, Schreibelt G, Drexhage J, Hazes T, Dijkstra CD, van der Valk P, de Vries HE (2008) Severe oxidative damage in multiple sclerosis lesions coincides with enhanced antioxidant enzyme expression. Free Radic Biol Med 45(12):1729–1737

    Article  PubMed  CAS  Google Scholar 

  22. Tasset I, Agüera E, Sánchez-López F, Feijóo M, Giraldo AI, Cruz AH, Gascón F, Túnez I (2012) Peripheral oxidative stress in relapsing-remitting multiple sclerosis. Clin Biochem 45(6):440–444

    Article  CAS  PubMed  Google Scholar 

  23. Ullevig S, Kim HS, Asmis R (2013) S-glutathionylation in monocyte and macrophage (dys)function. Int J Mol Sci 14(8):15212–15232

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Erden Inal M, Kanbak G, Sunal E (2001) Antioxidant enzyme activities and malondialdehyde levels related to aging. Clin Chim Acta 305:75–80

    Article  Google Scholar 

  25. 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):322–330

    Article  CAS  PubMed  Google Scholar 

  26. Miller AF (2004) Superoxide dismutases: active sites that save, but a protein that kills. Curr Opin Chem Biol 8(2):162–168

    Article  CAS  PubMed  Google Scholar 

  27. Namaki S, Mohsenzadegan M, Mirshafiey A (2009) Superoxide dismutase: a light horizon in treatment of multiple sclerosis. J Chin Clin Med 4(10):585–591

    CAS  Google Scholar 

  28. Afonso V, Champy R, Mitrovic D, Collin P, Lomri A (2007) Reactive oxygen species and superoxide dismutases: role in joint disease. Joint Bone Spine 74:324–329

    Article  CAS  PubMed  Google Scholar 

  29. Johnson F, Giulivi C (2005) Superoxide dismutases and their impact upon human health. Mol Aspects Med 26(4–5):340–52

    Article  CAS  PubMed  Google Scholar 

  30. Ramming T, Appenzeller-Herzog C (2013) Destroy and exploit: catalyzed removal of hydroperoxides from the endoplasmic reticulum. Int J Cell Biol 2013:180906

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Woolley JF, Stanicka J, Cotter TG (2013) Recent advances in reactive oxygen species measurement in biological systems. Trends Biochem Sci 38(11):556–565

    Article  CAS  PubMed  Google Scholar 

  32. Piloni NE, Fermandez V, Videla LA, Puntarulo S (2013) Acute iron overload and oxidative stress in brain. Toxicology 314(1):174–182

    Article  CAS  PubMed  Google Scholar 

  33. Korbecki J, Baranowska-Bosiacka I, Gutowska I, Chlubek D (2013) The effect of reactive oxygen species on the synthesis of prostanoids from arachidonic acid. J Physiol Pharmacol 64(4):409–421

    CAS  PubMed  Google Scholar 

  34. Ozyazgan S, Andican G, Erman H, Tuzcu A, Uzun H, Onal B, Ozyazgan Y (2013) Relation of protein oxidation parameters and disease activity in patients with Behçet’s disease. Clin Lab 59(7–8):819–825

    CAS  PubMed  Google Scholar 

  35. Feligioni M, Nisticò R (2013) SUMO: a (oxidative) stressed protein. Neuromolecular Med 15(4):707–719

    Article  CAS  PubMed  Google Scholar 

  36. Sitar ME, Aydin S, Cakatay U (2013) Human serum albumin and its relation with oxidative stress. Clin Lab 59(9–10):945–952

    CAS  PubMed  Google Scholar 

  37. Sadowska-Bartosz I, Adamczyk-Sowa M, Galiniak S, Mucha S, Pierzchala K, Bartosz G (2013) Oxidative modification of serum proteins in multiple sclerosis. Neurochem Int 63(5):507–516

    Article  CAS  PubMed  Google Scholar 

  38. Go YM, Jones DP (2013) Thiol/disulfide redox states in signaling and sensing. Crit Rev Biochem Mol Biol 48(2):173–181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Boersma BJ, D’Alessandro T, Benton MR, Kirk M, Wilson LS, Prasain J, Botting NP, Barnes S, Darley-Usmar VM, Patel RP (2003) Neutrophil myeloperoxidase chlorinates and nitrates soy isoflavones and enhances their antioxidant properties. Free Radic Biol Med 35(11):1417–1430

    Article  CAS  PubMed  Google Scholar 

  40. Perez Gutierrez RM, Flores Cotera LB, Gonzalez AM (2012) Evaluation of the antioxidant and anti-glycation effects of the hexane extract from piper auritum leaves in vitro and beneficial activity on oxidative stress and advanced glycation end-product-mediated renal injury in streptozotocin-treated diabetic rats. Molecules 17(10):11897–11919

    Article  CAS  PubMed  Google Scholar 

  41. Ferretti G, Bacchetti T (2011) Peroxidation of lipoproteins in multiple sclerosis. J Neurol Sci 311(1–2):92–97

    Article  CAS  PubMed  Google Scholar 

  42. Nam TG (2011) Lipid peroxidation and its toxicological implications. Toxicol Res 27(1):1–6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Yeagle PL (2013) Non-covalent binding of membrane lipids to membrane proteins. Biochim Biophys Acta. doi:10.1016/j.bbamem.2013.11.009

    PubMed  Google Scholar 

  44. Ren R, Hashimoto T, Mizuno M, Takigawa H, Yoshida M, Azuma T, Kanazawa K (2013) A lipid peroxidation product 9-oxononanoic acid induces phospholipase A2 activity and thromboxane A2 production in human blood. J Clin Biochem Nutr 52(3):228–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Koch M, Mostert J, Arutjunyan AV, Stepanov M, Teelken A, Heersema D, De Keyser J (2007) Plasma lipid peroxidation and progression of disability in multiple sclerosis. Eur J Neurol 14(5):529–533

    Article  CAS  PubMed  Google Scholar 

  46. Quintana FJ, Yeste A, Weiner HL, Covacu R (2012) Lipids and lipid-reactive antibodies as biomarkers for multiple sclerosis. J Neuroimmunol 248(1):53–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Pandey KB, Rizvi SI (2009) Protective effect of resveratrol on formation of membrane protein carbonyls and lipid peroxidation in erythrocytes subjected to oxidative stress. Appl Physiol Nutr Metab 34:1093–1097

    Article  PubMed  CAS  Google Scholar 

  48. Mitosek-Szewczyk K, Gordon-Krajcer W, Walendzik P, Stelmasiak Z (2010) Free radical peroxidation products in cerebrospinal fluid and serum of patients with multiple sclerosis after glucocorticoid therapy. Folia Neuropathol 48(2):116–122

    CAS  PubMed  Google Scholar 

  49. Pandey KB, Rizvi SI (2010) Protective effect of resveratrol on markers of oxidative stress in human erythrocytes subjected to in vitro oxidative insult. Phytother Res 24(S1):S11–S14

    Article  PubMed  Google Scholar 

  50. Sims-Robinson C, Hur J, Hayes JM, Dauch JR, Keller PJ, Brooks SV, Feldman EL (2013) The role of oxidative stress in nervous system aging. PLoS One 8(7):e68011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sarsour EH, Louise Kalen A, Goswami P (2013) Manganese superoxide dismutase regulates a redox cycle within the cell cycle. Antioxid Redox Sign. doi:10.1089/ars.2013.5303

    Google Scholar 

  52. Sheng Y, Chattopadhyay M, Whitelegge J, Valentine JS (2012) SOD1 aggregation and ALS: role of metallation states and disulfide status. Curr Top Med Chem 12(22):2560–2572

    Article  CAS  PubMed  Google Scholar 

  53. Mirshafiey A, Mohsenzadegan M (2009) Antioxidant therapy in multiple sclerosis. Immunopharmacol Immunotoxicol 31(1):13–29

    Article  CAS  PubMed  Google Scholar 

  54. Carillon J, Rouanet JM, Cristol JP, Brion R (2013) Superoxide dismutase administration, a potential therapy against oxidative stress related diseases: several routes of supplementation and proposal of an original mechanism of action. Pharm Res 30(11):2718–2728

    Article  CAS  PubMed  Google Scholar 

  55. Qi X, Hauswirth WW, Guy J (2007) Dual gene therapy with extracellular superoxide dismutase and catalase attenuates experimental optic neuritis. Mol Vis 13:1–11

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Heather LM, Teismann P (2009) Glutathione—a review on its role and significance in Parkinson’s disease. FASEB J 23(10):3263–3272

    Article  CAS  Google Scholar 

  57. Baud O, Greene AE, Li J, Wang H, Volpe JJ, Rosenberg PA (2004) Glutathione peroxidase-catalase cooperativity is required for resistance to hydrogen peroxide by mature rat oligodendrocytes. J Neurosci 24:1531–1540

    Article  CAS  PubMed  Google Scholar 

  58. Keller JN, Dimayuga E, Chen Q, Thorpe J, Gee J, Ding Q (2004) Autophagy, proteasomes, lipofuscin, and oxidative stress in the aging brain. Int J Biochem Cell Biol 36:2376–2391

    Article  CAS  PubMed  Google Scholar 

  59. Halldorsdottir SM, Kristinsson HG, Sveinsdottir H, Thorkelsson G, Hamaguchi PY (2013) The effect of natural antioxidants on haemoglobin-mediated lipid oxidation during enzymatic hydrolysis of cod protein. Food Chem 141(2):914–919

    Article  CAS  PubMed  Google Scholar 

  60. Penga F, Yanga Y, Liua J, Jianga Y, Zhua C, Denga X, Hua X, Chena X, Zhongb X (2012) Low antioxidant status of serum uric acid, bilirubin and albumin in patients with neuromyelitis optica. Eur J Neurol 19:277–283

    Article  Google Scholar 

  61. Han MH, Hwang SI, Roy DB, Lundgren DH, Price JV, Ousman SS, Fernald GH, Gerlitz B, Robinson WH, Baranzini SE, Grinnell BW, Raine CS, Sobel RA, Han DK, Steinman L (2008) Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets. Nature 451(7182):1076–1081

    Article  CAS  PubMed  Google Scholar 

  62. Pitt D, Werner P, Raine CS (2000) Glutamate excitotoxicity in a model of multiple sclerosis. Nature Med 6:67–70

    Article  CAS  PubMed  Google Scholar 

  63. Lambeth JD (2004) NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 4:181–189

    Article  CAS  PubMed  Google Scholar 

  64. Ilhan A, Akyol O, Gurel A, Armutcu F, Iraz M, Oztas E (2004) Protective effects of caffeic acid phenethyl ester against experimental allergic encephalomyelitis-induced oxidative stress in rats. Free Radic Biol Med 37:386–394

    Article  CAS  PubMed  Google Scholar 

  65. Witte ME, Bo L, Rodenburg RJ, Belien JA, Musters R, Hazes T, Wintjes LT, Smeitink JA, Geurts JJ, De Vries H, Van DV, van Horssen J (2009) Enhanced number and activity of mitochondria in multiple sclerosis lesions. J Pathol 219:193–204

    Article  PubMed  Google Scholar 

  66. Pahan K, Mondal S (2012) Crosstalk between nitric oxide and T helper cells. J Clin Cell Immunol 3:e109

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Satoh T, Lipton SA (2007) Redox regulation of neuronal survival mediated by electrophilic compounds. Trends Neurosci 1:37–45

    Article  CAS  Google Scholar 

  68. Yokoyama H, Yano R, Aoki E, Kato H, Araki T (2008) Comparative pharmacological study of free radical scavenger, nitric oxide synthase inhibitor, nitric oxide synthase activator and cyclooxygenase inhibitor against MPTP neurotoxicity in mice. Metab Brain Dis 23:335–349

    Article  CAS  PubMed  Google Scholar 

  69. Charil A, Filippi M (2007) Inflammatory demyelination and neurodegeneration in early multiple sclerosis. J Neurol Sci 259:7–15

    Article  CAS  PubMed  Google Scholar 

  70. Macco R, Pelizzoni I, Consonni A, Vitali I, Giacalone G, Martinelli Boneschi F, Codazzi F, Grohovaz F, Zacchetti D (2013) Astrocytes acquire resistance to iron-dependent oxidative stress upon proinflammatory activation. J Neuroinflamm 10(1):130

    Article  CAS  Google Scholar 

  71. Ortiz GG, Pacheco-Moisés FP, Bitzer-Quintero OK, Ramírez-Anguiano AC, Flores-Alvarado LJ, Ramírez-Ramírez V, Macias-Islas MA, Torres-Sánchez ED (2013) Immunology and oxidative stress in multiple sclerosis: clinical and basic approach. Clin Dev Immunol 2013:708659

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Ljubisavljevic S, Stojanovic I (2014) Neuroinflammation and demyelination from the point of nitrosative stress as a new target for neuroprotection. Rev Neurosci. doi:10.1515/revneuro-2014-0060

    Google Scholar 

  73. Garden GA, Moller T. Microglia biology in health and disease. J. Neuroimmune. Pharmacol. 2006; 1: 127–137

  74. Kornek B, Storch M, Weissert R, Wallstroem E, Stefferl A, Olsson T, Linington C, Schmidbauer M, Lassmann H (2000) Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive and remyelinated lesions. Amer J Pathol 157:267–276

    Article  CAS  Google Scholar 

  75. Androdias G, Reynolds R, Chanal M, Ritleng C, Confavreux C, Nataf S (2010) Meningeal T cells associate with diffuse axonal loss in multiple sclerosis spinal cords. Ann Neurol 68:465–476

  76. Knoferle J, Koch JC, Ostendorf T, Michel U, Planchamp V, Vutova P, Tönges L, Stadelmann C, Brück W, Bähr M, Lingor P (2010) Mechanisms of acute axonal degeneration in the optic nerve in vivo. Proc Natl Acad Sci U S A 107:6064–6069

    Article  PubMed  PubMed Central  Google Scholar 

  77. Shah D, Kiran R, Wanchu A, Bhatnagar A (2010) Oxidative stress in systemic lupus erythematosus: relationship to Th1 cytokine and disease activity. Immunol Lett 129:7–12

    Article  CAS  PubMed  Google Scholar 

  78. Fukuda M, Kanou F, Shimada N, Sawabe M, Saito Y, Murayama S, Hashimoto M, Maruyama N, Ishigami A (2009) Elevated levels of 4-hydroxynonenal-histidine Michael adduct in the hippocampi of patients with Alzheimer’s disease. Biomed Res 30:227–233

    Article  CAS  PubMed  Google Scholar 

  79. Miller E, Mrowicka M, Saluk-Juszczak J, Ireneusz M (2011) The level of isoprostanes as a non-invasive marker for in vivo lipid peroxidation in secondary progressive multiple sclerosis. Neurochem Res 36(6):1012–1016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Hendrickx DA, Koning N, Schuurman KG, van Strien ME, van Eden CG, Hamann J, Huitinga I (2013) Selective upregulation of scavenger receptors in and around demyelinating areas in multiple sclerosis. J Neuropathol Exp Neurol 72(2):106–118

    Article  CAS  PubMed  Google Scholar 

  81. Zhu X, Su B, Wang X, Smith MA, Perry G (2007) Causes of oxidative stress in Alzheimer disease. Cell Mol Life Sci 64:2202–2210

    Article  CAS  PubMed  Google Scholar 

  82. Xiang W, Weisbach V, Sticht H, Seebahn A, Bussmann J, Zimmermann R, Becker CM (2013) Oxidative stress-induced posttranslational modifications of human hemoglobin in erythrocytes. Arch Biochem Biophys 529:34–44

    Article  CAS  PubMed  Google Scholar 

  83. Oliveira SR, Kallaur AP, Simao ANC, Morimoto HK, Lopes J, Panis C, Petenucci DL, da Silva E, Cecchini R, Kaimen-Maciel DR, Reiche EM (2012) Oxidative stress in multiple sclerosis patients in clinical remission: association with the expanded disability status scale. J Neurol Sci 321(1–2):49–53

    Article  CAS  PubMed  Google Scholar 

  84. Przedborski S, Ischiropoulos H (2005) Reactive oxygen and nitrogen species: weapons of neuronal destruction in models of Parkinson’s disease. Antioxid Redox Signal 7:685–693

    Article  CAS  PubMed  Google Scholar 

  85. Kim SU, Park YH, Min JS, Sun HN, Han YH, Hua JM, Lee TH, Lee SR, Chang KT, Kang SW, Kim JM, Yu DY, Lee SH, Lee DS (2013) Peroxiredoxin I is a ROS/p38 MAPK-dependent inducible antioxidant that regulates NF-κB-mediated iNOS induction and microglial activation. J Neuroimmunol 259(1–2):26–36

    Article  CAS  PubMed  Google Scholar 

  86. Singh I, Paintlia AS, Khan M, Stanislaus R, Paintlia MK, Haq E, Singh AK, Contreras MA (2004) Impaired peroxisomal function in the central nervous system with inflammatory disease of experimental autoimmune encephalomyelitis animals and protection by lovastatin treatment. Brain Res 1022(1–2):1–11

    Article  CAS  PubMed  Google Scholar 

  87. Zeis T, Graumann U, Reynolds R, Schaeren-Wiemers N (2008) Normal-appearing white matter in multiple sclerosis is in a subtle balance between inflammation and neuroprotection. Brain 131:288–303

    Article  PubMed  Google Scholar 

  88. Sullivan GM, Mierzwa AJ, Kijpaisalratana N, Tang H, Wang Y, Song SK, Selwyn R, Armstrong RC (2013) Oligodendrocyte lineage and subventricular zone response to traumatic axonal injury in the corpus callosum. J Neuropathol Exp Neurol 72(12):1106–1125

    Article  PubMed  PubMed Central  Google Scholar 

  89. Fancy SP, Kotter MR, Harrington EP, Huang JK, Zhao C, Rowitch DH, Franklin RJ (2010) Overcoming remyelination failure in multiple sclerosis and other myelin disorders. Exp Neurol 225:18–23

    Article  CAS  PubMed  Google Scholar 

  90. Chaitanya GV, Omura S, Sato F, Martinez NE, Minagar A, Ramanathan M, Guttman BW, Zivadinov R, Tsunoda I, Alexander JS (2013) Inflammation induces neuro-lymphatic protein expression in multiple sclerosis brain neurovasculature. J Neuroinflamm 10(1):125

    Article  CAS  Google Scholar 

  91. Agrawal SM, Williamson J, Sharma R, Kebir H, Patel K, Prat A, Yong VW (2013) Extracellular matrix metalloproteinase inducer shows active perivascular cuffs in multiple sclerosis. Brain 136(6):1760–1777

    Article  PubMed  Google Scholar 

  92. Uccelli A, Pedemonte E, Narciso E, Mancardi G (2003) Biological markers of the inflammatory phase of multiple sclerosis. Neurol Sci 24(5):S271–274

    Article  PubMed  Google Scholar 

  93. Willard SS, Koochekpour S (2013) Glutamate signaling in benign and malignant disorders: current status, future perspectives, and therapeutic implications. Int J Biol Sci 9(7):728–742

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Mandolesi G, Musella A, Gentile A, Grasselli G, Haji N, Sepman H, Fresegna D, Bullitta S, De Vito F, Musumeci G, Di Sanza C, Strata P, Centonze D (2013) Interleukin-1β alters glutamate transmission at Purkinje cell synapses in a mouse model of multiple sclerosis. J Neurosci 33(29):12105–12121

    Article  CAS  PubMed  Google Scholar 

  95. Arend C, Brandmann M, Dringen R (2013) The antiretroviral protease inhibitor ritonavir accelerates glutathione export from cultured primary astrocytes. Neurochem Res 38(4):732–741

    Article  CAS  PubMed  Google Scholar 

  96. Fernandez-Fernandez S, Almeida A, Bolaños JP (2012) Antioxidant and bioenergetic coupling between neurons and astrocytes. Biochem J 443(1):3–11

    Article  CAS  PubMed  Google Scholar 

  97. Bizzozero OA, Ziegler JL, De Jesus G, Bolognani F (2006) Acute depletion of reduced glutathione causes extensive carbonylation of rat brain proteins. J Neurosci Res 83(4):656–667

    Article  CAS  PubMed  Google Scholar 

  98. Rumzan R, Wang JJ, Zeng C, Chen X, Li Y, Luo T, Lv F, Wang ZP, Hou H, Huang F (2013) Iron deposition in the precentral grey matter in patients with multiple sclerosis: a quantitative study using susceptibility-weighted imaging. Eur J Radiol 82(2):95–99

    Article  Google Scholar 

  99. Abo-Krysha N, Rashed L (2008) The role of iron dysregulation in the pathogenesis of multiple sclerosis: an Egyptian study. Mult Scler J 14(5):602–608

    Article  CAS  Google Scholar 

  100. Besler HT, Comoglu S (2003) Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis. Nutr Neurosci 6:189–196

    Article  CAS  PubMed  Google Scholar 

  101. Salemi G, Gueli MC, Vitale F, Battaglieri F, Guglielmini E, Ragonese P, Trentacosti A, Massenti MF, Savettieri G, Bono A (2010) Blood lipids, homocysteine, stress factors, and vitamins in clinically stable multiple sclerosis patients. Lipids Health Dis 9:19–21

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Wallberg M, Bergquist J, Achour A, Breij E, Harris RA (2007) Malondialdehyde modification of myelin oligodendrocyte glycoprotein leads to increased immunogenicity and encephalitogenicity. Eur J Immunol 37:1986–1995

    Article  PubMed  CAS  Google Scholar 

  103. Ljubisavljevic S, Stojanovic I, Pavlovic D, Milojkovic M, Sokolovic D, Stevanovic I, Petrovic A (2013) Suppression of the lipid peroxidation process in the CNS reduces neurological expression of experimentally induced autoimmune encephalomyelitis. Folia Neuropathol 51(1):51–57

    Article  CAS  PubMed  Google Scholar 

  104. Ljubisavljevic S, Stojanovic I, Vojinovic S, Stojanov D, Stojanovic S, Kocic G, Savic D, Cvetkovic T, Pavlovic D (2013) Cerebrospinal fluid and plasma oxidative stress biomarkers in different clinical phenotypes of neuroinflammatory acute attacks. Conceptual accession: from fundamental to clinic. Cell Mol Neurobiol 33(6):767–777

    Article  CAS  PubMed  Google Scholar 

  105. Bongarzone ER, Pasquini JM, Soto EF (1995) Oxidative damage to proteins and lipids of CNS myelin produced by in vitro generated reactive oxygen species. J Neurosci Res 41:213–221

    Article  CAS  PubMed  Google Scholar 

  106. Wuttge DM, Bruzelius M, Stemme S (1999) T-cell recognition of lipid peroxidation products breaks tolerance to self proteins. Immunology 98:273–279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Weismann D, Hartvigsen K, Lauer N, Bennett KL, Scholl HPN, Issa PC, Cano M, Brandstätter H, Tsimikas S, Skerka C, Superti-Furga G, Handa JT, Zipfel PF, Witztum JL, Christoph J (2011) Binder complement factor H binds malondialdehyde epitopes and protects from oxidative stress. Nature 478:76–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Kalyvas A, David S (2004) Cytosolic phospholipase A2 plays a key role in the pathogenesis of multiple sclerosis-like disease. Neuron 41:323–335

    Article  CAS  PubMed  Google Scholar 

  109. Marusic S, Leach MW, Pelker JW, Azoitei ML, Uozumi N, Cui J, Shen MW, DeClercq CM, Miyashiro JS, Carito BA, Thakker P, Simmons DL, Leonard JP, Shimizu T, Clark JD (2005) Cytosolic phospholipase A2α-deficient mice are resistant to experimental autoimmune encephalomyelitis. J Exp Med 202:841–851

  110. Jana A, Pahan K (2007) Oxidative stress kills human primary oligodendrocytes via neutral sphingomyelinase: implications for multiple sclerosis. J Neuroimmune Pharmacol 2:184–193

  111. Tavazzi B, Batocchi AP, Amorini AM, Nociti V, D’Urso S, Longo S, Gullotta S, Picardi M, Lazzarin G (2011) Serum metabolic profile in multiple sclerosis patients. Multiple Sclerosis International. doi:10.1155/2011/167156

    PubMed  PubMed Central  Google Scholar 

  112. Keles MS, Taysi S, Sen N, Aksoy H, Akçay F (2001) Effect of corticosteroid therapy on serum and CSF malondialdehyde and antioxidant proteins in multiple sclerosis. Can J Neurol Sci 28(2):141–143

    Article  CAS  PubMed  Google Scholar 

  113. Sbardella E, Greco A, Stromillo ML, Prosperini L, Puopolo M, Cefaro LA, Pantano P, De Stefano N, Minghetti L, Pozzilli C (2012) Isoprostanes in clinically isolated syndrome and early multiple sclerosis as biomarkers of tissue damage and predictors of clinical course. Mult Scler J. doi:10.1177/1352458512457721

    Google Scholar 

  114. Joseph JA, Shukitt-Hale B, Casadesus G, Fisher D (2005) Oxidative stress and inflammation in brain aging: nutritional considerations. Neurochem Res 30(6–7):927–935

    Article  CAS  PubMed  Google Scholar 

  115. Ferretti G, Bacchetti T, Principi F, Di Ludovico F, Viti B, Angeleri VA, Danni M, Provinciali L (2005) Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity. Mult Scler J 11:677–682

    Article  CAS  Google Scholar 

  116. Tsuda K (2012) Associations of oxidative stress and inflammation and their role in the regulation of membrane fluidity of red blood cells in hypertensive and normotensive men: an electron spin resonance investigation. Adv Biosci Biotechnol 3:1020–1027

    Article  CAS  Google Scholar 

  117. Hon GM, Hassan MS, van Rensburg SJ, Abel S, Marais DW, van Jaarsveld P, Smuts CM, Henning F, Erasmus RT, Matsha T (2009) Erythrocyte membrane fatty acids in patients with multiple sclerosis. Mult Scler J 15(6):759–762

    Article  CAS  Google Scholar 

  118. Koch M, Ramsaransing GS, Arutjunyan AV, Stepanov M, Teelken A, Heersema DJ, De Keyser J (2006) Oxidative stress in serum and peripheral blood leukocytes in patients with different disease courses of multiple sclerosis. J Neurol 253:483–487

    Article  CAS  PubMed  Google Scholar 

  119. de Freitas MV, de Oliveira MR, dos Santos DF, de Cássia Mascarenhas Netto R, Fenelon SB, Penha-Silva N (2010) Influence of the use of statin on the stability of erythrocyte membranes in multiple sclerosis. J Membr Biol 233(1–3):127–134

    Article  CAS  PubMed  Google Scholar 

  120. Pasichna EP, Morozova RP, Donchenko HV, Vinychuk SM, Kopchak OO (2007) Lipid peroxidation and antioxidant defence enzyme activity in multiple sclerosis. Ukr Biokhim Zh 79(5):165–174

    CAS  Google Scholar 

  121. Miler E, Walczak A, Majsterek I, Kędziora J (2013) Melatonin reduces oxidative stress in the erythrocytes of multiple sclerosis patients with secondary progressive clinical course. J Neuroimmunol. doi:10.1016/j.jneuroim.2013.02.012

    Google Scholar 

  122. Vani R, Shiva CS, Devi SA (2002) Oxidative stress in erythrocytes: a study on the effect of antioxidant mixtures during intermittent exposures to high altitude. Int J Biometeorol 54(5):553–562

    Article  Google Scholar 

  123. Acar A, Ugur Cevik M, Evliyaoglu O, Uzar E, Tamam Y, Arıkanoglu A, Yucel Y, Varol S, Onder H, Taşdemir N (2012) Evaluation of serum oxidant/antioxidant balance in multiple sclerosis. Acta Neurol Belg 112(3):275–280

    Article  PubMed  Google Scholar 

  124. Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, Jungers P, Descamps-Latscha B (1996) Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 49:1304–1313

    Article  CAS  PubMed  Google Scholar 

  125. Ghafourifar P, Mousavizadeh K, Parihar MS, Nazarewicz RR, Parihar A, Zenebe WJ (2008) Mitochondria in multiple sclerosis. Front Biosci 13:3116–3126

    Article  CAS  PubMed  Google Scholar 

  126. Fernandez O, Vermersch P (2011) From the fundamentals of multiple sclerosis to clinical management. J Neurol Sci 311:S1–2

    Article  PubMed  Google Scholar 

  127. Pentón-Rol G, Cervantes-Llanos M, Martínez-Sánchez G, Cabrera-Gómez JA, Valenzuela-Silva CM, Ramírez-Nuñez O, Casanova-Orta M, Robinson-Agramonte MA, Lopategui-Cabezas I, López-Saura PA (2009) TNF-α and IL-10 downregulation and marked oxidative stress in neuromyelitis optica. J Inflamm 6:18

    Article  Google Scholar 

  128. Ljubisavljevic S, Stojanovic I, Vojinovic S, Stojanov D, Stojanovic S, Cvetkovic T, Savic D, Pavlovic D (2013) The patients with clinically isolated syndrome and relapsing remitting multiple sclerosis show different levels of advanced oxidation protein products and total thiol content in plasma and CSF. Neurochem Int 62(7):988–997

    Article  CAS  PubMed  Google Scholar 

  129. Park B, Lee S, Kim E, Cho K, Riddell SR, Cho S, Ahn K (2006) Redox regulation facilitates optimal peptide selection by MHC class I during antigen processing. Cell 127:369–382

    Article  CAS  PubMed  Google Scholar 

  130. Heinecke JW, Li W, Daehnke HD, Goldstein JA (1993) Dityrosine, a specific marker of oxidation, in synthesized by the myeloperoxidase hydrogen peroxide system of human neutrophils and macrophages. J Biol Chem 268:4069–4077

    CAS  PubMed  Google Scholar 

  131. Davies U (1987) Protein damage and degradation by oxygen radicals. I. General aspects. J Biol Chem 262:9895–9901

    CAS  PubMed  Google Scholar 

  132. Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707–717

    Article  CAS  PubMed  Google Scholar 

  133. Lucas M, Rodríguez MC, Gata JM, Zayas MD, Solano F, Izquierdo G (2003) Regulation by interferon beta-1a of reactive oxygen metabolites production by lymphocytes and monocytes and serum sulfhydryls in relapsing multiple sclerosis patients. Neurochem Int 42:67–71

    Article  CAS  PubMed  Google Scholar 

  134. Frohman EM, Racke MK, Raine CS (2006) Multiple sclerosis—the plaque and its pathogenesis. N Engl J Med 354:942–55

    Article  CAS  PubMed  Google Scholar 

  135. Bramow S, Frischer JM, Lassmann H, Koch-Henriksen N, Lucchinetti CF, Sorensen PS, Laursen H (2010) Demyelination versus remyelination in progressive multiple sclerosis. Brain 133:2983–2998

    Article  PubMed  Google Scholar 

  136. Bisaga GN, Odinak MM, Boiko AN, Melnik YB, Popova NF (2012) Treatment of exacerbations of multiple sclerosis without the use of corticosteroids: the role of metabolic and antioxidant therapy. Neurosci Behav Physiol 42(2):123–127

    Article  CAS  Google Scholar 

  137. Bjartmar C, Trapp BD (2001) Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences. Curr Opin Neurol 14:271–278

    Article  CAS  PubMed  Google Scholar 

  138. De Stefano N, Narayanan S, Francis GS, Arnaoutelis R, Tartaglia MC, Antel JP, Matthews PM, Arnold DL (2001) Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch Neurol 58:65–70

    Article  PubMed  Google Scholar 

  139. Pandey KB, Rizvi SI (2012) Markers of oxidative stress in erythrocytes and plasma during aging in humans. Oxid Med Cell Longev 3(1):2–12

    Article  Google Scholar 

  140. Fiorini A, Koudriavtseva T, Bucaj E, Coccia R, Foppoli C, Giorgi A, Schininà ME, Di Domenico F, De Marco F, Perluigi M (2013) Involvement of oxidative stress in occurrence of relapses in multiple sclerosis: the spectrum of oxidatively modified serum proteins detected by proteomics and redox proteomics analysis. PLoS One 8(6):e65184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Shelton MD, Mieyal JJ (2008) Regulation by reversible S-glutathionylation: molecular targets implicated in inflammatory diseases. Mol Cell 25:332–346

    CAS  Google Scholar 

  142. Garcia J, Han D, Sancheti H, Yap LP, Kaplowitz N, Cadenas E (2010) Regulation of mitochondrial glutathione redox status and protein glutathionylation by respiratory substrates. J Biol Chem 285:39646–39654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Lu SC (2009) Regulation of glutathione synthesis. Mol Aspects Med 30:42–59

  144. Castegna A, Palmieri L, Spera I, Porcelli V, Palmieri F, Fabis-Pedrini MJ, Kean RB, Barkhouse DA, Curtis MT, Hooper DC (2011) Oxidative stress and reduced glutamine synthetase activity in the absence of inflammation in the cortex of mice with experimental allergic encephalomyelitis. Neuroscience 185:97–105

  145. Tao F, Lu SD, Zhang LM, Huang YL, Sun FY (2001) Role of excitatory amino acid transporter 1 in neonatal rat neuronal damage induced by hypoxia-ischemia. Neuroscience 102(3):503–513

    Article  CAS  PubMed  Google Scholar 

  146. Albrecht P, Lewerenz J, Dittmer S, Noack R, Maher P, Methner A (2010) Mechanisms of oxidative glutamate toxicity: the glutamate/cystine antiporter system xc¯ as a neuroprotective drug target. CNS Neurol Disord Drug Targets 9(3):373–382

    Article  CAS  PubMed  Google Scholar 

  147. Werner P, Pitt D, Raine CS (2001) Multiple sclerosis: altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage. Ann Neurol 50(2):169–180

    Article  CAS  PubMed  Google Scholar 

  148. Calabrese V, Scapagnini G, Ravagna A, Bella R, Foresti R, Bates TE, Giuffrida Stella AM, Pennisi G (2002) Nitric oxide synthase is present in the cerebrospinal fluid of patients with active multiple sclerosis and is associated with increases in cerebrospinal fluid protein nitrotyrosine and S-nitrosothiols and with changes in glutathione levels. J Neurosci Res 70:580–587

    Article  CAS  PubMed  Google Scholar 

  149. Moss DW, Bates TE (2001) Activation of murine microglial cell lines by lipopolysaccharide and interferon-γ causes NO-mediated decreases in mitochondrial and cellular function. Eur J Neurosci 13:529–538

    Article  CAS  PubMed  Google Scholar 

  150. Kronke M, Adam-Klages S (2002) Role of caspases in TNF-mediated regulation of cPLA2. FEBS Lett 531:18–22

    Article  CAS  PubMed  Google Scholar 

  151. Pautz A, Art J, Hahn S, Nowag S, Voss C, Kleinert H (2010) Regulation of the expression of inducible nitric oxide synthase. Nitric Oxide 23(2):75–93

    Article  CAS  PubMed  Google Scholar 

  152. Steinert JR, Chernova T, Forsythe ID (2010) Nitric oxide signaling in brain function, dysfunction, and dementia. Neuroscientist 16:435–452

    Article  CAS  PubMed  Google Scholar 

  153. Ouyang M, Shen X (2006) Critical role of ASK1 in the 6- hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells. J Neurochem 97:234–244

    Article  CAS  PubMed  Google Scholar 

  154. Whiteman M, Chua YL, Zhang D, Duan W, Liou YC, Armstrong JS (2006) Nitric oxide protects against mitochondrial permeabilization induced by glutathione depletion: role of S-nitrosylation? Biochem Biophys Res Commun 339:255–262

    Article  CAS  PubMed  Google Scholar 

  155. Paige JS, Xu G, Stancevic B, Jaffrey SR (2008) Nitrosothiol reactivity profiling identifies S-nitrosylated proteins with unexpected stability. Chem Biol 15:1307–1316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Romero JM, Bizzozero OA (2009) Intracellular glutathione mediates the denitrosylation of protein nitrosothiols in the rat spinal cord. J Neurosci Res 87:701–709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Marozkina NV, Gaston B (2011) S-Nitrosylation signaling regulates cellular protein interactions. Biochim Biophys Acta. doi:10.1016/j.bbagen.2011.06.017

    PubMed  PubMed Central  Google Scholar 

  158. Motterlini R, Foresti R, Bassi R, Calabrese V, Clark JE, Green CJ (2000) Endothelial heme oxygenase-1 induction by hypoxia. Modulation by inducible nitric-oxide synthase and S-nitrosothiols. J Biol Chem 275:13613–13620

    Article  CAS  PubMed  Google Scholar 

  159. Muller B, Kleschyov AL, Alencar JL, Vanin A, Stoclet JC (2002) Nitric oxide transport and storage in the cardiovascular system. Ann NY Acad Sci 962:131–139

    Article  CAS  PubMed  Google Scholar 

  160. Kim SF, Huri DA, Snyder SH (2005) Inducible nitric oxide synthase binds, S-nitrosylates and activates cyclooxygenase-2. Science 310:1966–1970

    Article  CAS  PubMed  Google Scholar 

  161. Knott AB, Bossy-Wetzel E (2009) Nitric oxide in health and disease of the nervous system. Antioxid Redox Signal 11:541–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Liu L, Yan Y, Zeng M, Zhang J, Hanes MA, Ahearn G, McMahon TJ, Dickfeld T, Marshall HE, Que LG, Stamler JS (2004) Essential roles of S-nitrosothiols in vascular homeostasis and endotoxic shock. Cell 116:617–628

    Article  CAS  PubMed  Google Scholar 

  163. Foster MW, McMahon TJ, Stamler JS (2003) S-Nitrosylation in health and disease. Trends Mol Med 9:160–168

    Article  CAS  PubMed  Google Scholar 

  164. Witherick J, Wilkins A, Scolding N, Kemp K (2010) Mechanisms of oxidative damage in multiple sclerosis and a cell therapy approach to treatment. Autoimmune Diseases. doi:10.4061/2011/164608

    PubMed  PubMed Central  Google Scholar 

  165. Liu JS, Zhao ML, Brosnan CF, Lee SC (2001) Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions. Am J Pathol 158:2057–2066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Sparaco M, Gaeta LM, Tozzi G, Bertini E, Pastore A, Simonati A, Santorelli FM, Piemonte F (2006) Protein glutathionylation in human central nervous system: potential role in redox regulation of neuronal defense against free radicals. J Neurosci Res 83:256–263

    Article  CAS  PubMed  Google Scholar 

  167. Boullerne AI, Rodrıguez JJ, Touil T, Brochet B, Schmidt S, Abrous NR, Le Moal M, Pua JR, Jensen MA, Mayo W, Arnason BGW, Petry KG (2002) Anti-S-nitrosocysteine antibodies are a predictive marker for demyelination in experimental autoimmune encephalomyelitis: implications for multiple sclerosis. J Neurosci 22(1):123–132

    CAS  PubMed  Google Scholar 

  168. Khan M, Sekhon B, Giri S, Jatana M, Gilg AG, Ayasolla K, Elango C, Singh AK, Singh I (2005) S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke. J Cereb Blood Flow Metab 25(2):177–192

    Article  CAS  PubMed  Google Scholar 

  169. Hendriks JJ, Teunissen CE, De Vries HE, Dijkstra CD (2005) Macrophages and neurodegeneration. Brain Res Rev 48:185–195

    Article  CAS  PubMed  Google Scholar 

  170. Ischiropoulos H, Beckman JS (2003) Oxidative stress and nitration in neurodegeneration: cause, effect, or association? J Clin Invest 111:163–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Foster MW, Hess DT, Stamler JS (2009) Protein S-nitrosylation in health and disease: a current perspective. Trends Mol Med 15:391–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Ljubisavljevic S, Stojanovic I, Pavlovic R, Stojnev S, Stevanovic I, Sokolovic D, Pavlovic D (2012) The reduced glutathione and S-nitrosothiols levels in acute phase of experimental demyelination—pathophysiological approach and possible clinical relevancy. Neuroscience 219:175–182

    Article  CAS  PubMed  Google Scholar 

  173. Prasad R, Giri S, Nath N, Singh I, Singh AK (2007) GSNO attenuates EAE disease by S-nitrosylation-mediated modulation of endothelial-monocyte interactions. Glia 55:65–77

    Article  PubMed  Google Scholar 

  174. Richter-Addo GB, Legzdins P, Burstyn J (2002) Introduction: nitric oxide chemistry. Chem Rev 102(4):857–860

    Article  CAS  PubMed  Google Scholar 

  175. Jomova K, Vondrakova D, Lawson M, Valko M (2010) Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem 345(1–2):91–104

    Article  CAS  PubMed  Google Scholar 

  176. Kidd PM (2001) Multiple sclerosis, an autoimmune inflammatory disease: prospects for its integrative management. Altern Med Rev 6:54066

    Google Scholar 

  177. Grinberg L, Fibach E, Amer J, Atlas D (2005) N-acetylcysteine amide, a novel cell-permeating thiol, restores cellular glutathione and protects human red blood cells from oxidative stress. Free Radical Bio Med 38:1136–1145

    Article  CAS  Google Scholar 

  178. Deneke SM (2000) Thiol-based antioxidants. Curr Top Cell Regul 36:151–180

    Article  CAS  PubMed  Google Scholar 

  179. Hvaring C, Vujicic S, Aasly JO, Feinstein DL, White LR, Boullerne AI (2013) IgM to S-nitrosylated protein is found intrathecally in relapsing-remitting multiple sclerosis. J Neuroimmunol 256(1–2):77–83

    Article  CAS  PubMed  Google Scholar 

  180. Lin SX, Lisi L, Dello Russo C, Polak PE, Sharp A, Weinberg G, Kalinin S, Feinstein DL (2011) The anti-inflammatory effects of dimethyl fumarate in astrocytes involve glutathione and haem oxygenase-1. ASN Neuro 3(2):75–84. doi:10.1042/AN20100033

    Article  CAS  Google Scholar 

  181. Nath N, Morinaga O, Singh I (2010) S-nitrosoglutathione a physiologic nitric oxide carrier attenuates experimental autoimmune encephalomyelitis. J Neuroimmune Pharm 2:240–251

    Article  Google Scholar 

  182. Staron A, Makosa G, Koter-Michalak M (2012) Oxidative stress in erythrocytes from patients with rheumatoid arthritis. Rheumatol Int 32:331–334

    Article  CAS  PubMed  Google Scholar 

  183. Calabrese V, Scapagnini G, Ravagna A, Bella R, Butterfield DA, Calvani M, Pennisi G, Giuffrida Stella AM (2003) Disruption of thiol homeostasis and nitrosative stress in the cerebrospinal fluid of patients with active multiple sclerosis: evidence for a protective role of acetylcarnitine. Neurochem Res 28(9):1321–1328

    Article  CAS  PubMed  Google Scholar 

  184. Scapagnini G, Foresti R, Calabrese V, Giuffrida Stella AM, Green CJ, Motterlini R (2002) Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-l inducers. Mol Pharmacol 61:554–561

    Article  CAS  PubMed  Google Scholar 

  185. Stojanovic I, Ljubisavljevic S, Stevanovic I, Pavlovic R, Cvetkovic T, Djordjevic V, Pavlovic D, Vojinovic S, Basic J (2012) Nitric oxide-mediated signalization and nitrosative stress in neuropathology. J Med Biochem 31(4):295–300

    Article  CAS  Google Scholar 

  186. van Meeteren ME, Teunissen CE, Dijkstra CD, van Tol EAF (2005) Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur J Clin Nutr 59:1347–1361

    Article  PubMed  CAS  Google Scholar 

  187. Ljubisavljevic S, Stojanovic I, Cvetkovic T, Vojinovic S, Stojanov D, Stojanovic D, Bojanic V, Stokanovic D, Pavlovic D (2014) The glutathione homeostasis disruption of erythrocytes, but not glutathione peroxidase activity changes, is closely accompanied with neurological and radiological scoring of acute CNS inflammation. Neuroimmunomodulation 21:13–20

    Article  CAS  PubMed  Google Scholar 

  188. Adamczyksowa M, Sowa P, Pierzchala K, Polaniak R, Labuzroszak B (2012) Antioxidative enzymes activity and malondialdehyde concentration. During mitoxantrone therapy in multiple sclerosis patients. J Physiol Pharmacol 63(6):683–690

    CAS  Google Scholar 

  189. Miller E, Mrowicka M, Zołyński K, Kedziora J (2009) Oxidative stress in multiple sclerosis. Pol Merkur Lekarski 162:499–502

    Google Scholar 

  190. Straif D, Werz DO, Kellner R, Bahr U, Steinhilber D (2000) Glutathione peroxidase-1 but not -4 is involved in the regulation of cellular 5-lipoxygenase activity in monocytic cells. Biochem J 349:455–461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Jana A, Hogan EL, Pahan K (2009) Ceramide and neurodegeneration: susceptibility of neurons and oligodendrocytes to cell damage and death. J Neurol Sci 278(1):5–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Liu Y, Hao W, Letiembre M, Walter S, Kulanga M, Neumann H, Fassbender K (2006) Suppression of microglial inflammatory activity by myelin phagocytosis: role of p47-PHOX-mediated generation of reactive oxygen species. J Neurosci 26(50):12904–12913

    Article  CAS  PubMed  Google Scholar 

  193. van Horssen J, Witte ME, Schreibelt G, de Vries HE (2011) Radical changes in multiple sclerosis pathogenesis. BBA – Mol Basis Dis 1812(2):141–150

    Article  CAS  Google Scholar 

  194. Tajouri L, Mellick AS, Ashton KJ, Tannenberg AEG, Nagra RM, Tourtellotte WW, Griffiths LR (2003) Quantitative and qualitative changes in gene expression patterns characterize the activity of plaques in multiple sclerosis. Mol Brain Res 119(2):170–183

    Article  CAS  PubMed  Google Scholar 

  195. Yoshida E, Mokunoa K, Aoki S, Takahashi A, Riku S, Murayama T, Yanagi T, Kato K (1994) Cerebrospinal fluid levels of superoxide dismutases in neurological diseases detected by sensitive enzyme immunoassays. J Neurol Sci 124:25–31

    Article  CAS  PubMed  Google Scholar 

  196. Gallan PM, Carrascosa A, Gussinye M, Dominguez C (2003) Biomarkers of diabetes associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complication. Free Radical Bio Med 34:1563–1574

    Article  CAS  Google Scholar 

  197. Zagórski T, Dudek I, Berkan L, Mazurek M, Kedziora J, Chmielewski H (1991) Superoxide dismutase (SOD-1) activity in erythrocytes of patients with multiple sclerosis. Neurol Neurochir Pol 25(6):725–730

    PubMed  Google Scholar 

  198. Rowiński R, Kozakiewicz M, Kędziora-Kornatowska K, Hübner-Woźniak E, Kędziora J (2013) Markers of oxidative stress and erythrocyte antioxidant enzyme activity in older men and women with differing physical activity. Exp Gerontol 48:1141–1146

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the grant from the scientific project number 41018 financed by the Ministry of Education and Science, Republic of Serbia.

Conflict of Interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Srdjan Ljubisavljevic.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ljubisavljevic, S. Oxidative Stress and Neurobiology of Demyelination. Mol Neurobiol 53, 744–758 (2016). https://doi.org/10.1007/s12035-014-9041-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-014-9041-x

Keywords

Navigation