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2012 | 72 | 1 |

Tytuł artykułu

Correlation of nitric oxide levels in the cerebellum and spinal cord of experimental autoimmune encephalomyelitis rats with clinical symptoms

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Experimental autoimmune encephalomyelitis (EAE) is a well-established cell-mediated autoimmune inflammatory disease of the CNS, which has been used as a model of the human demyelinating disease. EAE is characterized by infiltration of the CNS by lymphocytes and mononuclear cells, microglial and astrocytic hypertrophy, and demyelination which cumulatively contribute to clinical expression of the disease. EAE was induced in female Sprague-Dawley rats, 3 months old (300 g ± 20 g), by immunization with myelin basic protein (MBP) in combination with Complete Freund's adjuvant (CFA). The animals were divided into 7 groups: control, EAE, CFA, EAE + aminoguanidine (AG), AG, EAE + N-acetyl-L-cysteine (NAC) and NAC. The animals were sacrificed 15 days after EAE induction, and the level of nitric oxide (NO') production was determined by measuring nitrite and nitrate concentrations in 10% homogenate of cerebellum and spinal cord. Obtained results showed that the level of NO' was significantly increased in all examined tissues of the EAE rats compared to the control and CFA groups. Also, AG and NAC treatment decreased the level of NO' in all tissues compared to the EAE group. The level of NO' is increased significantly in the spinal cord compared to the cerebellum. The clinical course of the EAE was significantly decreased in the EAE groups treated with AG and NAC during the development of the disease compared to EAE group and its correlates with the NO' level in cerebellum and spinal cord. The findings of our work suggest that NO' and its derivatives play an important role in multiple sclerosis (MS). It may be the best target for new therapies in human demyelinating disease and recommend the new therapeutic approaches based on a decreased level of NO' during the course of MS.

Słowa kluczowe

Wydawca

-

Rocznik

Tom

72

Numer

1

Opis fizyczny

p.33-39,fig.,ref.

Twórcy

  • Clinic of Neurology, University Clinical Centre of Nis, Nis, Serbia
  • Institute for Pathophysiology, Faculty of Medicine, University of Nis, Nis, Serbia
  • Institute for Biochemistry, Faculty of Medicine, Universty of Nis, Nis, Serbia
autor
  • Institute for Biochemistry, Faculty of Medicine, Universty of Nis, Nis, Serbia
  • Institute for Pathophysiology, Faculty of Medicine, University of Nis, Nis, Serbia
autor
  • Clinic of Neurology, University Clinical Centre of Nis, Nis, Serbia
autor
  • Institute for Biochemistry, Faculty of Medicine, Universty of Nis, Nis, Serbia
  • Military Medical Academy, Belgrade, Serbia

Bibliografia

  • Beckman JS, Chen J, Crow JP, Ye YZ (1994) Reactions of nitric oxide, superoxide and peroxynitrite with superox¬ide dismutase in neurodegeneration. Prog Brain Res 103: 371-380.
  • Beckman JS, Koppenol WH (1996) Nitric oxide, superox¬ide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271: C1424-C37.
  • Bishop A, Hobbs K, Eguchi A, Jeffrey S, Smallwood L, Pennie C, Anderson J, Estevez A (2009) Differential sensi¬tivity of oligodendrocytes and motor neurons to reactive nitrogen species: implications for multiple sclerosis. J Neurochem 109: 93-104.
  • Blanco S, Molina FJ, Castro L, Del Moral ML, Hernandez R, Jimenez A, Alma Rus A, Martinez-Lara E, Siles E, Peinado MA (2010) Study of the nitric oxide system in the rat cerebellum during aging. BMC Neurosci 11: 78.
  • Bo L, Dawson TM, Wesselingh S, Mork S, Choi S, Kong PA, Hanley D, Trapp BD (1994) Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann Neurol 36: 778-786.
  • Boullerne AI, Petry KG, Meynard M, Geffard M (1995) Indirect evidence for nitric oxide involvement in multiple sclerosis by characterization of circulating antibodies directed against conjugated S-nitrosocysteine. J Neuroimmunol 60: 117-124.
  • Brenner T, Brocke S, Szafer F, Sobel RA, Parkinson JF, Perez DH, Steinman L (1997) Inhibition of nitric oxide synthase for treatment of experimental autoimmune encephalomyelitis. J Immunol 158: 2940-2946.
  • Brown G, Bal-Price AM (2003) Inflammatory neurodegen¬eration mediated by nitric oxide, glutamate and mito¬chondria. Mol Neurobiol 27: 325-355.
  • Buchwalow IB (2001) Increasing the power of immunohis- tochemistry. Proc Roy Microsc Soc 36: 57-59.
  • 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 lev¬els. J Neurosci Res 70: 580-587.
  • Cross AH, Manning PT, Keeling RM, Schmidt RE, Misko TP (1998) Peroxynitrite formation within the central ner¬vous system in active multiple sclerosis. J Neuroimmunol 88: 45-56.
  • De Groot CJ, Ruuls SR, Theeuwes JW, Dijkstra CD, Van Der Valk P (1997) Immunocytochemical characterization of the expression of inducible and constitutive isoforms of nitric oxide synthase in demyelinating multiple sclero¬sis lesions. J Neuropathol Exp Neurol 56: 10-20.
  • Farias AS, de la Hoz C, Castro FR, Oliveira EC, Ribeiro dos Reis JR, Silva JS, Langone F, Santos LM (2007) Nitric oxide and TNFa effects in experimental autoimmune encephalomyelitis demyelination. Neuroimmuno- modulation 14: 32-38.
  • Fenyk-Melody JE, Garrison AE, Brunnert SR, Weidner JR, Shen F, Shelton BA, Mudgett JS (1998) Experimental autoimmune encephalomyelitis is exacerbated in mice lacking the NOS2 gene. J Immunol 160: 2940-2946.
  • Henderson A, Barnett M, Parratt J, Prineas J (2009) Multiple sclerosis: Distribution of inflammatory cells in newly forming lesions. Ann Neurol 66: 739-753.
  • Jack C, Ruffini F, Bar-Or A, Antel JP (2005) Microglia and multiple sclerosis. J Neurosci Res 81: 363-373.
  • Kahl KG, Zielasek J, Uttenthal LO, Rodrigo J, Toyka KV, Schmidt HH (2003) Protective role of the cytokine-inducible isoform of nitric oxide synthase induction and nitrosative stress in experimental autoimmune encephalomy- elitis of the DA rat. J Neurosci Res 73: 198-205.
  • Kim JH, Budde MD, Liang HF, Klein RS, Russell JH, Cross AH, Song SK (2006) Detecting axon damage in spinal cord from a mouse model of multiple sclerosis. Neurobiol Dis 21: 626-632.
  • Knowles RG, Moncada S (1994) Nitric oxide synthases in mammals. Biochem J 298: 249-248.
  • Kornek B, Storch MK, 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. Am J Pathol 157: 267-276.
  • Lin RF, Lin TS, Tilton RG, Cross AH (1993) Nitric oxide localized to spinal cords of mice with experimental aller¬gic encephalomyelitis: an electron paramagnetic reso¬nance study. J Exp Med 178: 643-648.
  • Ljubisavljevic S, Stojanovic I, Pavlovic D, Sokolovic D, Stevanovic I (2011) Aminoguanidine and N-Acetyl- Cysteine supress oxidative and nitrosative stress in EAE rat brains. Redox Rep 16: 166-172.
  • Losy J, Niezgoda A, Wender M (1999) Increased serum levels of soluble PECAM-1 in multiple sclerosis patients with brain gadoliniumenhancing lesions. J Neuroimmunol 99: 169-172.
  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193: 265-275.
  • Malabendu J, Kalipada P (2005) Redox regulation of cytokine-mediated inhibition of myelin gene expression in human primary oligodendrocytes. Free Radic Biol Med 39: 823-831.
  • Marques C, Cheeran M, Palmquist J, Hu S, Lokensgard J (2008) Microglia are the major cellular source of inducible nitric oxide synthase during experimental herpes encephalitis. J Neurovirol 14: 229-238.
  • Mitrovic B, Ignarro LJ, Montestruque S, Smoll A, Merrill JE (1994) Nitric oxide as a potential pathological mecha¬nism in demyelination: Its differential effects on primary glial cells in vitro. Neuroscience 61: 575-585.
  • Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43: 109-142.
  • Muzhou WU, Tsirka SE (2009) Endothelial NOS-deficient mice reveal dual roles for nitric oxide during experimen¬tal autoimmune encephalomyelitis. Glia 57: 1204-1215.
  • Napoli I, Neumann H (2010) Protective effects of microglia in multiple sclerosis. Exp Neurol 225: 24-28.
  • Nathan C, Xie QW (1994) Nitric oxide synthase: roles, tolls and control. Cell 78: 919.
  • Navaro-Gonzalvez JA, Garcia-Benayas C, Arenas J (1998) Semiautomated measurement of nitrate in biological flu¬ids. Clin Chem 44: 679-681.
  • Okuda Y, Sakoda S, Fujimura H, Yanagihara T (1997) Nitric oxide via an inducible isoform of nitric oxide synthase is a possible factor to eliminate cells from the central ner¬vous system of mice with experimental allergic encepha¬lomyelitis. J. Neuroimmunol 73: 107.
  • Okuda Y, Sakoda S, Fujimura H, Yanagihara T (1998) Aminoguanidine, a selective inhibitor of the inducible nitric oxide synthase, has different effects on experimen¬tal allergic encephalomyelitis in the induction and pro¬gression phase. J Neuroimmunol 81: 201-210.
  • Pahan K, Sheikh FG, Namboodiri AM, Singh I (1998) N-acetyl cysteine inhibits induction of NO production by endotoxin or cytokine stimulated rat peritoneal mac- rophages, C6 glial cells and astrocytes. Free Radic Biol Med 24: 39-48.
  • 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: 75-93.
  • Raine CS, Barnett LA, Brown A, McFarlin DE (1980) Neuropathology of experimental allergic encephalomyelitis in bred strains of mice. Lab Invest 43: 150.
  • Ruuls SR, Van der Linden S, Sontrop K, Huitinga I, Dijkstra CD (1996) Aggravation of experimental allergic encephalomyelitis (EAE) by administration of nitric oxide (NO) synthase inhibitors. Clin Exp Immunol 103: 467-474.
  • Saito S, Kidd GJ, Trapp BD, Dawson TM, Bredt DS, Wilson DA, Traystman RJ, Snyder SH, Hanley DF (1994) Rat spinal cord neurons contain nitric oxide synthase. Neuroscience 59: 447-456.
  • Sajad M, Zargan J, Chawla R, Umar S, Sadaqat M, Khan H (2009) Hippocampal neurodegeneration in experimental autoimmune encephalomyelitis (EAE): potential role of inflammation activated myeloperoxidase. Mol Cell Biochem 328: 183-188.
  • Smith KJ, Kapoor R, Paul A (1999) Demyelination: The role of reactive oxygen and nitrogen species. Brain Pathol 9: 69-92.
  • Thiel VE, Audus KL (2001) Nitric oxide and blood-brain barrier integrity. Antioxid Redox Signal 3: 273-78.
  • Willenborg DO, Staykova MA (1998) Approaches to the treatment of central nervous system autoimmune disease using specific neuroantigen. Immunol Cell Biol 76: 91.
  • Xu LY, Yang JS, Link H, Xiao BG (2001) SIN-1, a nitric oxide donor, ameliorates experimental allergic encephalomyelitis in Lewis rats in the incipient phase: the importance of the time window. J Immunol 166: 5810¬5816.
  • Yamashita T, Ando Y, Obayashi K, Uchino M, Ando M (1997) Changes in nitrite and nitrate (NO2/-/NO3/-) lev¬els in cerebrospinal fluid of patients with multiple sclero¬sis. J Neurol Sci 153: 32-34.

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Bibliografia

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