Lipoic acid decreases inflammation and confers neuroprotection in experimental autoimmune optic neuritis

被引:54
作者
Chaudhary, Priya [1 ]
Marracci, Gail [1 ]
Yu, Xiaolin [1 ]
Galipeau, Danielle [1 ]
Morris, Brooke [1 ]
Bourdette, Dennis [1 ,2 ]
机构
[1] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA
[2] Dept Vet Affairs Med Ctr, Neurol Serv, Portland, OR USA
关键词
Lipoic acid; Optic neuritis; EAON; Multiple sclerosis; Neuroprotection; T-CELL MIGRATION; MULTIPLE-SCLEROSIS; AXONAL DEGENERATION; SPINAL-CORD; MODEL; ENCEPHALOMYELITIS; CAMP; NEURODEGENERATION; ACTIVATION;
D O I
10.1016/j.jneuroim.2010.12.002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Lipoic acid (LA) is an antioxidant that is effective in treating experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). C57BL/6 mice with EAE develop experimental autoimmune optic neuritis (EAON), which models acute optic neuritis in humans. Here we determined whether LA is therapeutically effective in EAON. We immunized C57BL/6 mice with MOG 35-55 peptide. Mice received either daily subcutaneous injections of LA (100 mg/kg) or saline in early or late suppression paradigms. In the early suppression paradigm, optic nerve cross-sections showed 14.9 +/- 3.8% (mean +/- SEM) damage in mice receiving saline (n = 7) and 2.0 +/- 0.4% damage in mice given LA (n = 7, p = 0.001). In the late suppression paradigm, optic nerve sections showed 24.6 +/- 3.5% damage in mice treated with saline (n = 7) and 8.4 +/- 2.5% in mice treated with LA (n = 7, p = 0.004). Thus a dramatic reduction in axonal injury was seen after LA administration in both experimental paradigms. Compared with saline treated mice with EAON, optic nerves from mice receiving LA had significantly fewer CD4+ and CD11b+ cells in both paradigms. This study provides a rationale for investigating the therapeutic efficacy of IA in acute optic neuritis in humans. Published by Elsevier B.V.
引用
收藏
页码:90 / 96
页数:7
相关论文
共 38 条
[1]
Acute inflammatory demyelinating optic neuritis - Evidence-based visual and neurological considerations [J].
Abou Zeid, Nuhad ;
Matti, M. Tariq .
NEUROLOGIST, 2008, 14 (04) :207-223
[2]
Age related optic nerve axonal loss in adult Brown Norway rats [J].
Cepurna, WO ;
Kayton, RJ ;
Johnson, EC ;
Morrison, JC .
EXPERIMENTAL EYE RESEARCH, 2005, 80 (06) :877-884
[3]
Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis [J].
Chaudhary, P ;
Marracci, GH ;
Bourdette, DN .
JOURNAL OF NEUROIMMUNOLOGY, 2006, 175 (1-2) :87-96
[4]
Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients [J].
Dutta, R ;
McDonough, J ;
Yin, XG ;
Peterson, J ;
Chang, A ;
Torres, T ;
Gudz, T ;
Macklin, EB ;
Lewis, DA ;
Fox, RJ ;
Rudick, R ;
Mirnics, K ;
Trapp, BD .
ANNALS OF NEUROLOGY, 2006, 59 (03) :478-489
[5]
Cyclophilin D inactivation protects axons in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis [J].
Forte, Michael ;
Gold, Bruce G. ;
Marracci, Gail ;
Chaudhary, Priya ;
Basso, Emy ;
Johnsen, Dustin ;
Yu, Xiaolin ;
Fowlkes, Jonathan ;
Bernardi, Paolo ;
Bourdette, Dennis .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (18) :7558-7563
[6]
Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research [J].
Gold, Ralf ;
Linington, Christopher ;
Lassmann, Hans .
BRAIN, 2006, 129 :1953-1971
[7]
Effect of geranylgeranylacetone on optic neuritis in experimental autoimmune encephalomyelitis [J].
Guo, Xiaoli ;
Harada, Chikako ;
Namekata, Kazuhiko ;
Kikushima, Kenji ;
Mitamura, Yoshinori ;
Yoshida, Hiroshi ;
Matsumoto, Yoh ;
Harada, Takayuki .
NEUROSCIENCE LETTERS, 2009, 462 (03) :281-285
[8]
Optic nerve degeneration in experimental autoimmune encephalomyelitis [J].
Guy, John .
OPHTHALMIC RESEARCH, 2008, 40 (3-4) :212-216
[9]
Behavioral and pathological outcomes in MOG 35-55 experimental autoimmune encephalomyelitis [J].
Jones, M. V. ;
Nguyen, T. T. ;
DeBoy, C. A. ;
Gniffin, J. W. ;
Whartenby, K. A. ;
Kerr, D. A. ;
Calabresi, P. A. .
JOURNAL OF NEUROIMMUNOLOGY, 2008, 199 (1-2) :83-93
[10]
MYELIN BASIC PROTEIN-SPECIFIC T-CELLS INDUCE DEMYELINATING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN BUFFALO RATS [J].
JONES, RE ;
BOURDETTE, DN ;
OFFNER, H ;
VANDENBARK, AA .
JOURNAL OF NEUROIMMUNOLOGY, 1990, 30 (01) :61-69