Hypoxia-like tissue injury as a component of multiple sclerosis lesions

Hans Lassmann, Hans Lassmann

Abstract

Recent data suggest that the mechanisms of demyelination and tissue damage in multiple sclerosis (MS) are heterogenous. In this review, evidence is discussed, which show that in a subset of multiple sclerosis patients the central nervous system (CNS) lesions show profound similarities to tissue alterations found in acute white matter stroke, thus suggesting that a hypoxia-like metabolic injury is a pathogenetic component in a subset of inflammatory brain lesions. Both, vascular pathology as well as metabolic disturbances induced by toxins of activated macrophages and microglia may be responsible for such lesions in multiple sclerosis.

References

    1. Lucchinetti C., Brück W., Parisi J., Scheithauer B., Rodriguez M., Lassmann H. A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 117 cases. Brain. 1999;122:2279–2295.
    1. Lucchinetti C., Brück W., Parisi J., Scheithauer B., Rodriguez M., Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 2000;47:707–717.
    1. Lassmann H. Multiple sclerosis pathology. In: Compston A., editor. McAlpine's multiple sclerosis. 3rd ed. Churchill Livingstone; London: 1998. pp. 323–358.
    1. Gay F., Drye T., Dick G., Esiri M. The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of primary demyelinating lesion. Brain. 1997;120:1461–1483.
    1. Babbe H., Roers A., Waisman A., Lassmann H., Goebels N., Hohlfeld R. Clonal expansion of CD8+ T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. J. Exp. Med. 2000;192:393–404.
    1. Brueck W., Porada P., Poser S., Rieckmann P., Hanefeld F., Kretzschmar H.A. Monocyte/macrophage differentiation in early multiple sclerosis lesions. Ann. Neurol. 1995;38:788–796.
    1. Ferguson B., Matyszak M.K., Esiri M.M., Perry V.H. Axonal damage in acute multiple sclerosis lesions. Brain. 1997;120:393–399.
    1. Trapp B.D., Peterson J., Ransohoff R.M., Rudick R., Mork S., Bo L. Axonal transection in the lesions of multiple sclerosis. N. Engl. J. Med. 1998;338:278–285.
    1. Kornek B., Storch M., Weissert R., Wallstroem E., Stefferl A., Olsson T. Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive and remyelinated lesions. Am. J. Pathol. 2000;157:267–276.
    1. Prineas J.W., Graham J.S. Multiple sclerosis: capping of surface immunoglobulin G on macrophages engaged in myelin breakdown. Ann. Neurol. 1981;10:149–158.
    1. Storch M., Stefferl A., Brehm U., Weissert R., Wallström E., Kerschensteiner M. Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology. Brain Pathol. 1998;8:681–694.
    1. Genain C.P., Cannella B., Hauser S.L., Raine C.S. Autoantibodies to MOG mediate myelin damage in MS. Nat. Med. 1999;5:170–175.
    1. Lucchinetti C., Brück W., Rodriguez M., Lassmann H. Distinct patterns of multiple sclerosis pathology indicates heterogeneity in pathogenesis. Brain Pathol. 1996;6:259–274.
    1. Chataway J., Sawcer S., Coraddu F., Feakes R., Broadley S., Jones H. Evidence that allelic variants of the spinocerebellar ataxia type 2 gene influence susceptibility to multiple sclerosis. Neurogenetics. 1999;2:91–96.
    1. Fazekas F., Strasser-Fuchs S., Schmidt H., Enzinger C., Ropele S., Lechner A. Apolipoprotein E genotype related differences in brain lesions of multiple sclerosis. J. Neurol. Neurosurg. Psychiatry. 2000;69:25–28.
    1. Hogh O., Oturai A., Schreiber K., Blinkenberg M., Jorgensen O., Ryder L. Apolipoprotein E and multiple sclerosis: impact of the epsilon-4 allele on susceptibility, clinical type and progression. Mult. Scler. 2000;6:226–230.
    1. Mojon D., Fujihara K., Hirano M., Miller C., Lincoff N., Jacobs D. Leber's hereditary optic neuropathy mitochondrial DNA mutations in familial multiple sclerosis. Graefes Arch. Clin. Exp. Ophthalmol. 1999;237:348–350.
    1. Giess R., Maurer M., Linker R., Gold R., Warmuth-Metz M., Toyka K.V. Association of a null mutation in the CNTF gene with early onset of multiple sclerosis. Arch. Neurol. 2002;59:407–409.
    1. Linker R.A., Maurer M., Gaupp S., Martini R., Holtmann B., Giess R. CNTF is a major protective factor in demyelinating CNS disease: a neurotrophic cytokine as modulator in neuroinflammation. Nat. Med. 2002;8:620–624.
    1. Itoyama Y., Sternberger N., Webster H., Quarles R., Cohen S., Richardson E. Immunocytochemical observation on the distribution of myelin-associated glycoprotein and myelin basic protein in multiple sclerosis lesions. Ann. Neurol. 1980;7:167–177.
    1. Ludwin S.K., Johnson E.S. Evidence of a “dying-back” gliopathy in demyelinating disease. Ann. Neurol. 1981;9:301–305.
    1. Webster H.deF., Shi H., Lassmann H. Immunocytochemical study of myelin associated glycoprotein (MAG), myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in chronic relapsing experimental allergic encephalomyelitis (EAE) Acta Neuropathol. (Berl.) 1985;65:177–189.
    1. Rodriguez M. Central nervous system demyelination and remyelination in multiple sclerosis and viral models of disease. J. Neuroimmunol. 1992;40:255–263.
    1. Itoyama Y., Webster H.deF., Sternberger N.H., Richardson E.P., Walker D.L., Quarles R.H. Distribution of papovavirus, myelin-associated glycoprotein and myelin basic protein in progressive multifocal leukoencephalopathy lesions. Ann. Neurol. 1982;11:396–407.
    1. Semenza G.L. Surviving ischemia: adaptive responses mediated by hypoxia-inducible factor 1. J. Clin. Invest. 2000;106:809–812.
    1. Aboul-Enein F, Rauschka H, Kornek B, Stadelmann C, Stefferl A, Brück W, et al. Preferential loss of myelin-associated glycoprotein reflects hypoxia-like white matter damage in stroke and inflammatory brain diseases. J Neuropathol Exp Neurol [in press].
    1. Broman T. Blood brain barrier damage in multiple sclerosis. Supra-vital test observations. Acta Neurol. Scand. 1964;10:21–24.
    1. Kwon E.E., Prineas J.W. Blood brain barrier abnormalities in longstanding multiple sclerosis lesions. An immunohistochemical study. J. Neuropathol. Exp. Neurol. 1994;53:625–636.
    1. Kermode A.G., Thompson A.J., Tofts B., MacManus D.G., Kendall B.E., Kingsley D.P. Breakdown of the blood brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. Brain. 1990;113:1477–1489.
    1. Prineas J.W., McDonald I.W. Demyelinating diseases. In: Graham D.I., Lantos P.L., editors. Greenfield's neuropathology. 6th ed. Arnold; London: 1997. pp. 813–896.
    1. Millan M.T., Geczy C., Stuhlmeier K.M., Goodman D.J., Ferran C., Bach F.H. Human monocytes activate porcine endothelial cells, resulting in increased E-selectin, interleukin-8, monocyte chemotactic protein-1 and plasminogen activator inhibitor-type 1 expression. Transplantation. 1997;63:421–429.
    1. Kopp C.W., Siegel J.B., Hancock W.W., Anrather J., Winkler H., Geczy C.L. Effect of porcine endothelial tissue factor pathway inhibitor on human coagulation factors. Transplantation. 1997;63:749–758.
    1. Huseby E.S., Liggitt D., Brabb T., Schnabel B., Ohlen C., Goverman J. A pathogenic role for myelin-specific CD8 (+) T-cells in a model for multiple sclerosis. J. Exp. Med. 2001;194:669–676.
    1. Vass K., Lassmann H. Intrathecal application of interferon gamma progressive appearance of MHC antigens within the rat nervous system. Am. J. Pathol. 1990;137:789–800.
    1. Putnam T.J. The pathogenesis of multiple sclerosis: a possible vascular factor. N. Engl. J. Med. 1933;209:786–790.
    1. Wakefield A., More L., Difford J., McLaughlin J. Immunohistochemical study of vascular injury in acute multiple sclerosis. J. Clin. Pathol. 1994;47:129–133.
    1. Courville C.B. Concentric sclerosis. In: Vinken P.J., Bruyn G.W., editors. vol. 9. Elsevier; Amsterdam: 1970. pp. 437–451. (Handbook of clinical neurology).
    1. Lucchinetti C.F., Mandler R., McGavern D., Brück W., Gleich G., Ransohoff R.M. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain. 2002;125:1450–1461.
    1. Adams C.W. Perivascular iron deposition and other vascular damage in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry. 1988;51:260–265.
    1. Lipton S.A. Neuronal injury associated with HIV-1: approaches and treatment. Annu. Rev. Pharmacol. Toxicol. 1998;38:159–177.
    1. Werner P., Pitt P., Raine C.S. Multiple sclerosis: altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage. Ann. Neurol. 2001;50:169–180.
    1. Smith T., Groom A., Zhu B., Turski L. Autoimmune encephalomyelitis ameliorated by AMPA antagonists. Nat. Med. 2000;6:62–66.
    1. Pitt D., Werner P., Raine C.S. Glutamate excitotoxicity in a model of multiple sclerosis. Nat. Med. 2000;6:67–70.
    1. De Groot C.J., Ruuls S.R., Theeuwes J.W., Dijkstra C.D., van der Valk P. Immunocytochemical characterization of the expression of inducible and constitutive isoforms of nitric oxide synthase in demyelinating multiple sclerosis lesions. J. Neuropathol. Exp. Neurol. 1997;56:10–20.
    1. Liu J.S., Zhao M.L., Brosnan C.F., Lee S.C. Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions. Am. J. Pathol. 2001;158:2057–2066.
    1. Bitsch A., Wegener C., Da Costa C., Bunkowski S., Reimers C.D., Prange H.W. Lesion development in Marburg's type of acute multiple sclerosis: from inflammation to demyelination. Mult. Scler. 1999;5:138–146.
    1. Cross A.H., Manning P.T., Keeling R.M., Schmidt R.E., Misko T.P. Peroxynitrite formation within the central nervous system in active multiple sclerosis. J. Neuroimmunol. 1998;88:45–56.
    1. Merrill J.E., Ignarro L.J., Sherman M.P., Melinek J., Lane T.E. Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J. Immunol. 1993;151:2132–2141.
    1. Redford E.J., Kapoor R., Smith K.J. Nitric oxide donors reversibly block axonal conduction: demyelinated axons are especially susceptible. Brain. 1997;120:2149–2157.
    1. Smith K.J., Kapoor R., Hall S.M., Davies M. Electrically active axons degenerate when exposed to nitric oxide. Ann. Neurol. 2001;49:470–476.
    1. Li Z., Chapleau M.W., Bates J.N., Bielefeldt K., Lee H.-C., Abboud F.M. Nitric oxide as an autocrine regulator of sodium currents in baroreceptor neurons. Neuron. 1998;20:1039–1049.
    1. Mitrovic B., Ignarro L.J., Montestruque S., Smoll A., Merrill J.E. Nitric oxide as a potential pathological mechanism in demyelination: its differential effects on primary glial cells in vitro. Neuroscience. 1994;61:575–585.
    1. Brorson J.R., Schumacker P.T., Zhang H. Nitric oxide acutely inhibits neuronal energy production. J. Neurosci. 1999;19:147–158.
    1. Beltran B., Mathur A., Duchen M.R., Erusalimsky J.D., Moncada S. The effect of nitric oxide on cell respiration: a key to understanding its role in cell survival or death. Proc. Natl. Acad. Sci. U. S. A. 2000;97(26):14602–14607.
    1. Kimura H., Weisz A., Kurashima Y., Hashimoto K., Ogura T., D'Acquisto F. Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible factor 1 activity by nitric oxide. Blood. 2000;97:9082–9087.

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