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  • Print publication year: 2009
  • Online publication date: July 2016

Chapter 5 - Immune effector heterogeneity in multiple sclerosis and related CNS inflammatory demyelinating disorders

from Section 2: - Autoimmunity


Abdoul-Enein F, et al. Preferential loss of myelin-associated glycoprotein reflects hypoxia-like white matter damage in stroke and inflammatory brain diseases. J Neuropathol Exp Neurol 2003; 62(1): 25–33.
Abdoul-Enein F, et al. [Review] Mitochondrial damage and histotoxic hypoxia: A pathway of tissue injury in inflammatory brain disease? Acta Neuropathol (Berl) 2005; 109(1): 49–55.
Aktas O, et al. Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL. Neuron 2005; 46(3): 421–32.
Albert M, et al. Extensive cortical remyelination in patients with chronic multiple sclerosis. Brain Path Brain Pathol 2007; 17(2): 129–38.
Allen IV, McKeown SR. A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis. J Neurol Sci 1979; 41(1): 81–91.
Ambrosini E, Aloisi F. Chemokines and glial cells: A complex network in the central nervous system. Neurochem Res 2004; 29: 1017–38.
Amiry-Moghaddam M, et al. An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain. Proc Natl Acad Sci USA 2003; 100(4): 2106–11.
Anthony DC, et al. Differential matrix metalloproteinase expression in cases of MS and stroke. Neuropath Appl Neurobiol 1997; 23: 406–15.
Babbe H, et al. Clonal expansions 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(3): 393–404.
Baig S, et al. Multiple sclerosis: Cells secreting antibodies against myelin-associated glycoprotein are present in cerebrospinal fluid. Scand J Immunol 1991; 33(1): 73–9.
Balashov KE, et al. CCR5(+) and CXCR3(+) T cells are increased in multiple sclerosis and their ligands MIP-1alpha and IP-10 are expressed in demyelinating brain lesions. Proc Natl Acad Sci USA 1999; 96(12): 6873–8.
Barnett MH, Prineas JW. Pathological Heterogeneity in Multiple Sclerosis: A Reflection of Lesion Stage? Ann Neurol 2004; 56(2): 309.
Bechtold DA, Smith KJ. Sodium-mediated axonal degeneration in inflammatory demyelinating disease. J Neurol Sci 2005; 233(1–2): 27–35. Review.
Berger T, et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 2003; 349(2): 139–45.
Bezzi P, Volterra A. A neuron–glia signaling network in the active brain. Curr Opin Neurobiol 2001; 11(3): 387–94.
Bezzi P, et al. Prostaglandins stimulate calcium-dependent glutamate release in astrocytes. Nature 1998; 391(6664): 281–5.
Bjartmar CWJ, Trapp BD. Axonal loss in the pathology of MS: Consequences for understanding the progressive phase of the disease. J Neurol Sci 2003; 206(2): 165–71.
Bieber A, et al. Genetically dominant spinal cord repair in a murine model of chronic progressive multiple sclerosis. J Neuropathol Exp Neurol 2005; 64(1): 46–57.
Bitsch A, et al. Lesion development in Marburg’s type of acute multiple sclerosis: From inflammation to demyelination. Mult Scler 1999; 5: 138–46.
Bitsch A, et al. Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain 2000; 123 (Pt 6): 1174–83.
Bitsch A, et al. A longitudinal MRI study of histopathologically defined hypointense multiple sclerosis lesions. Ann Neurol 2001; 49(6): 793–6.
Blakemore WF, et al. The presence of astrocytes in areas of demyelination influences remyelination following transplantation of oligodendrocyte progenitors. Exp Neurol 2003; 184(2): 955–63.
Bo L, et al. Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann Neurol 1994; 36(5): 778–86.
Bo L, et al. Subpial demyelination in the cerebral cortex of multiple sclerosis patients. J Neuropathol Exp Neurol 2003a; 62(7): 723–32.
Bo L, et al. Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration. Mult Scler 2003b; 9(4): 323–31.
Bonetti B, Raine CS. Multiple sclerosis: Oligodendrocytes display cell death-related molecules in situ but do not undergo apoptosis. Ann Neurol 1997; 42(1): 74–84.
Booss J, et al. Immunohistological analysis of T lymphocyte subsets in the central nervous system in chronic progressive multiple sclerosis. J Neurol Sci 1983; 62(1–3): 219–32.
Bostock H, Sears T. The internodal axon membrane: Electrical excitability and continuous conduction in segmental demyelination. J Physiol (Lond) 1978; 280: 273–301.
Bourquin C, et al. Myelin oligodendrocyte glycoprotein-DNA vaccination induces antibody-mediated autoaggression in experimental autoimmune encephalomyelitis. Eur J Immunol 2000; 30(12): 3663–71.
Boven LA, et al. Myelin-laden macrophages are anti-inflammatory, consistent with foam cells in multiple sclerosis. Brain 2006; 129(2): 517–26.
Brink BP, et al. The pathology of multiple sclerosis is location-dependent: no significant complement activation is detected in purely cortical lesions. J Neuropathol Exp Neurol 2005; 64(2): 147–55.
Broman T. Blood–brain barrier damage in multiple sclerosis supravital test-observations. Acta Neurol Scand 1964; 40: 21–4.
Brown GC. Nitric oxide inhibition of mitochondrial respiration and its role in cell death. Free Rad Biol Med 2002; 33(11): 1440–50.
Brown GC, et al. Interactions between nitric oxide, oxygen, reactive oxygen species and reactive nitrogen species. Biochem Soc Trans 2006; 34(5): 953–6.
Bruck W, et al. Monocyte/macrophage differentiation in early multiple sclerosis lesions. Ann Neurol 1995; 38(5): 788–96.
Bruck W, et al. Inflammatory central nervous system demyelination: Correlation of magnetic resonance imaging findings with lesion pathology. Ann Neurol 1997; 42(5): 783–93.
Brueck W, et al. Oligodendrocytes in the early course of multiple sclerosis. Ann Neurol 1994; 35(1): 65–73.
Burgoon MP, Owens GP. B cells in multiple sclerosis. Front Biosci 2004; 9(3): 786–96.
Chang A, et al. Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med 2002; 346(3): 165–73.
Christians ES, et al. Heat shock factor 1 and heat shock proteins: Critical partners in protection against acute cell injury. Crit Care Med 2002; 30(Suppl. 1): S43–50.
Coleman M. Axon degeneration mechanisms: Commonality amid diversity. Nat Rev Neurosci 2005; 6(11): 889–98.
Conde JR, Streit WJ. Microglia in the aging brain. J Neuropathol Exp Neurol 2006; 65(3): 199–203.
Confavreux C, et al. Relapses and progression of disability in multiple sclerosis. N Engl J Med 2000; 343(20): 1430–8.
Corcione A, et al. Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis. Proc Natl Acad Sci USA 2004; 101: 11064–9.
Craner MJ, et al. Co-localization of sodium channel Nav1.6 and the sodium–calcium exchanger at sites of axonal injury in the spinal cord in EAE. Brain 2004a; 127(2): 294–303.
Craner, MJ, et al. 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 USA 2004b; 101(21): 8168–73.
Crocker SJ, et al. Persistent macrophage/microglial activation and myelin disruption after experimental autoimmune encephalomyelitis in tissue inhibitor of metalloproteinase-1-deficient mice. Am J Pathol 2006; 169: 2104–16.
Cross A, et al. B cells and antibodies in CNS demyelinating disease. J Neuroimmunol 2001; 112: 1–14.
Cuzner M, et al. The expression of tissue-type plasminogen activator, matrix metalloproteinases and endogenous inhibitors in the central nervous system in multiple sclerosis: Comparison of stages in lesion evolution. J Neuropathol Exp Neurol 1996; 55: 1194–204.
De Rosbo NK, Ben-Nun A. T-cell responses to myelin antigens in multiple sclerosis; relevance of the predominant autoimmune reactivity to myelin oligodendrocyte glycoprotein. J Autoimmunol 1998; 11(4): 287–99.
Diemel LT, et al. Macrophages in CNS remyelination: Friend or foe? Neurochem Res 1998; 23(3): 341–7.
Dowling P, et al. Involvement of the CD95 (APO-1/Fas) receptor/ligand system in multiple sclerosis brain. J Exp Med 1996; 184(4): 1513–8.
D’Souza S, et al. Multiple sclerosis: Fas signaling in oligodendrocyte cell death. J Exp Med 1996; 184: 2361–70.
Dutta R, et al. Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann Neurol 2006; 59: 478–89.
Egg R, et al. Anti-MOG and anti-MBP antibody subclasses in multiple sclerosis. Mult Scler 2001; 7(5): 285–9.
Evangelou N, et al. Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis. Ann Neurol 2000; 47(3): 391–5.
Ferguson B, et al. Axonal damage in acute multiple sclerosis lesions. Brain 1997; 120: 393–9.
Flavin MP, et al. Soluble macrophage factors trigger apoptosis in cultured hippocampal neurons. Neuroscience 1997; 80: 437–448.
Flavin MP, et al. Microglial tissue plasminogen activator (tPA) triggers neuronal apoptosis in vitro. Glia 2000; 29: 347–54.
Fogdell A, et al. Linkage analysis of HLA class II genes in Swedish multiplex families with multiple sclerosis. Neurology 1997; 48(3): 758–62.
Foote AK, Blakemore WF. Inflammation stimulates remyelination in areas of chronic demyelination. Brain 2005; 128(3): 528–39.
Forstermann U, et al. Nitric oxide synthase: Expression and expressional control of the three isoforms. Naunyn Schmiedebergs Arch Pharmacol 1995; 352(4): 351–64.
Foster R, et al. Reorganization of the axon membrane in demyelinated peripheral nerve fibers: Morphological evidence. Science 1980; 210: 661–3.
Franklin RJ. Why does remyelination fail in multiple sclerosis? Nat Rev Neurosci 2002; 3(9): 705–14.
Friede RL, Bruck W. Macrophage functional properties during myelin degradation. Adv Neurol 1993; 59: 327–36.
Friese M, et al. Humanized mouse models for organ-specific autoimmune diseases. Curr Opin Immunol 2006; 18(6): 704–09.
Friese M, Fugger L. Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy? Brain 2005; 128(8): 1747–63.
Gay FW, et al. The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of the primary demyelinating lesion. Brain 1997; 120: 1461–83.
Gaertner S, et al. Antibodies against glycosylated native MOG are elevated in patients with multiple sclerosis. Neurology 2004; 63(12): 2381–3.
Geurts JJ, et al. Altered expression patterns of group I and II metabotropic glutamate receptors in multiple sclerosis. Brain 2003; 126(8): 1755–66.
Giordana MT, et al. Abnormal ubiquitination of axons in normally myelinated white matter in multiple sclerosis brain. Neuropathol Appl Neurobiol 2002; 28(1): 35–41.
Giovannoni G, et al. The potential role of nitric oxide in multiple sclerosis. Mult Scler 1998; 4: 212–6.
Glabinski AR, Ransohoff RM. Chemokines and chemokine receptors in CNS pathology. J Neurovirol 1999a; 5(1): 3–12.
Glabinski AR, Ransohoff RM. Sentries at the gate: Chemokines and the blood–brain barrier. J Neurovirol 1999b; 5(6): 623–34.
Gold R, et al. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 2006; 129(8): 1953–71.
Hafler DA, et al. Multiple sclerosis. Immunol Rev 2005; 204: 208–31.
Haase CG, et al. The fine specificity of the myelin oligodendrocyte glycoprotein autoantibody response in patients with multiple sclerosis and normal healthy controls. J Neuroimmunol 2001; 114(1–2): 220–5.
Hill KE, et al. Inducible nitric oxide synthase in chronic active multiple sclerosis plaques: Distribution, cellular expression and association with myelin damage. J Neuroimmunol 2004; 151(1–2): 171–9.
Hochmeister S, et al. Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis. J Neuropathol Exp Neurol 2006; 65(9): 855–65.
Hoftberger R, et al. Expression of major histocompatibility complex class I molecules on the different cell types in multiple sclerosis lesions. Brain Pathol 2004; 14: 43–50.
Hohlfeld R, Wekerle H. Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines. Proc Natl Acad Sci USA 2004; 101(Suppl 2): 14599–606.
Holley JE, et al. Astrocyte characterization in the multiple sclerosis glial scar. Neuropathol Appl Neurobiol 2003; 29(5): 434–44.
Hollsberg P, et al. Induction of anergy in CD8 T cells by B cell presentation of antigen. J Immunol 1996; 157(12): 5269–76.
Huseby ES, et al. A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple sclerosis. J Exp Med 2001; 194: 669–76.
Jung J, et al. Molecular characterization of an aquaporin cDNA from brain: Candidate osmoreceptor and regulator of water balance. Proc Natl Acad Sci USA 1994; 91: 13052–6.
Kabat EA, et al. Quantitative estimation of albumin and gamma globulin in normal and pathological cerebrospinal fluid by immunochemical methods. Am J Med 1948; 4: 653–62.
Karni A, et al. Elevated levels of antibody to myelin oligodendrocyte glycoprotein is not specific for patients with multiple sclerosis. Arch Neurol 1999; 56(3): 311–5.
Keegan M, et al. Relation between humoral pathological changes in multiple sclerosis and response to therapeutic plasma exchange. Lancet 2005; 366(9485): 579–82.
Kerlero De Rosbo N, et al. Predominance of the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis: Reactivity to the extracellular domain of MOG is directed against three main regions. Eur J Immunol 1997; 27(11): 3059–69.
Kermode AG, et al. Heterogeneity of blood-brain barrier changes in multiple sclerosis. An MRI study with gadolinium-DTPA enhancement. Neurology 1990; 40: 229.
Kerschensteiner M, et al. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: A neuroprotective role of inflammation? J Exp Med 1999; 189(5): 865–70.
Kidd D, et al. Cortical lesions in multiple sclerosis. Brain 1999; 122(Pt 1): 17–26.
Kivisakk P, et al. High numbers of perforin mRNA expressing CSF cells in MS with gadolinium-enhancing brain MRI lesions. Acta Neurol Scand 1999; 100(1): 18–24.
Kornek B, et al. Multiple sclerosis and chronic autoimmune encephalomyelitis: A comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am J Pathol 2000; 157(1): 267–76.
Kotter MR, et al. Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination. Glia 2001; 35(3): 204–12.
Kuhlmann T et al. Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain 2002; 125(10): 2202–12.
Kutzelnigg A, Lassmann H. Cortical demyelination in multiple sclerosis: A substrate for cognitive deficits? J Neurol Sci 2006; 245(1–2): 123–6.
Kutzelnigg A, et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 2005; 128(11): 2705–12.
Kwon EE, Prineas JW. Blood–brain barrier abnormalities in longstanding multiple sclerosis lesions. An immunohistochemical study. J Neuropathol Exp Neurol 1994; 53(6): 625–36.
Lalive PH, Genain CP. Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis. Proc Natl Acad Sci USA 2006; 103(7): 2280–5.
Lampasona V, et al. Similar low frequency of anti-MOG IgG and IgM in MS patients and healthy subjects. Neurology 2004; 62: 2092–4.
Lassmann H, et al. Experimental allergic encephalomyelitis: The balance between encephalitogenic T lymphocytes and demyelinating antibodies determines size and structure of demyelinated lesions. Acta Neuropathol (Berl) 1988; 75(6): 566–76.
Lassmann H. Axonal injury in multiple sclerosis. J Neurol Neurosurg Psychiatry 2003; 74: 695–7.
Lassmann H, Ransohoff RM. The CD4-Th1 model for multiple sclerosis: A critical re-appraisal. Trends Immunol 2004; 25(3): 132–7.
Lassman H. Multiple sclerosis pathology: Evolution of pathogenetic concepts. Brain Pathol 2005; 15(3): 217–22.
Lennon V, et al. A serum autoantibody marker of neuromyelitis optica: Distinction from multiple sclerosis. Lancet 2004; 364(9451): 2106–12.
Lennon V, et al. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005; 202(4): 473–7.
Lim ET, et al. Anti-myelin antibodies do not allow earlier diagnosis of multiple sclerosis. Mult Scler 2005; 11(4): 492–4.
Linberg RL, et al. The expression profile of matrix metalloproteinases and their inhibitors in lesions and normal appearing white matter of multiple sclerosis. Brain 2001; 124: 1743–53.
Lindert RB, et al. Multiple sclerosis: B- and T-cell responses to the extracellular domain of the myelin oligodendrocyte glycoprotein. Brain 1999; 122 (Pt 11): 2089–100.
Linington C, et al. Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am J Pathol 1988; 130(3): 443–54.
Linker RA, et al. CNTF is a major protective factor in demyelinating CNS disease: A neurotrophic cytokine as modulator in neuroinflammation. Nat Med 2002; 8: 620–4.
Liu J, et al. Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions. Am J Pathol 2001; 158: 2057–66.
Lovas G, et al. Axonal changes in chronic demyelinated cervical spinal cord plaques. Brain 2000; 123(2): 308–17.
Lu W, et al. Involvment of tissue plasminogen activator in onset and effector phases of experimental allergic encephalomyelitis. J Neurosci 2002; 22: 10781–9.
Lucchinetti C, et al. A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases. Brain 1999; 122 (12): 2279–95.
Lucchinetti C, et al. Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination. Ann Neurol 2000; 47(6): 707–17.
Lucchinetti CF, et al. A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain 2002; 125(7): 1450–61.
Lucchinetti CF, et al. Evidence for pathogenic heterogeneity in multiple sclerosis. Ann Neurol 2004; 56(2): 308.
Lucchinetti CF, et al. The pathology of multiple sclerosis. Neurol Clin 2005; 23(1): 77–105, vi.
Ludwin S, et al. Evidence of a “dying back” gliopathy in demyelinating disease. Ann Neurol 1981; 9: 301–05.
Luster AD. Chemokines – chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338(7): 436–45.
Mahad DJ, et al. Expression of chemokine receptors CCR1 and CCR5 reflects differential activation of mononuclear phagocytes in pattern II and pattern III multiple sclerosis lesions. J Neuropathol Exp Neurol 2004; 63(3): 262–73.
Mahad D, et al. Modulating CCR2 and CCL2 at the blood–brain barrier: Relevance for multiple sclerosis pathogenesis. Brain 2006; 129(Pt 1): 212–23.
Mandler RN, et al. Devic’s neuromyelitis optica: A clinicopathological study of 8 patients. Ann Neurol 1993; 34(2): 162–8.
Mantegazza R, et al. Anti-MOG autoantibodies in Italian multiple sclerosis patients: Specificity, sensitivity and clinical association. Int Immunol 2004; 16(4): 559–65.
Mantovani A, et al. Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 2002; 23: 549–55.
Mantovani A, et al. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 2004; 25(12): 677–86.
Mantovani A, et al. Macrophage polarization comes of age. Immunity 2005; 23(4): 344–6.
Marta CB, et al. Pathogenic myelin oligodendrocyte glycoprotein antibodies recognize glycosylated epitopes and perturb oligodendrocyte physiology. Proc Natl Acad Sci USA 2005a; 102(39): 13992–7.
Marta CB, et al. Signaling cascades activated upon antibody cross-linking of myelin oligodendrocyte glycoprotein: potential implications for multiple sclerosis. J Biol Chem 2005b; 280(10): 8985–93.
Martino G, et al. Cells producing antibodies specific for myelin basic protein region 70–89 are predominant in cerebrospinal fluid from patients with multiple sclerosis. Eur J Immunol 1991; 12: 2971–6.
Martino G, et al; Cytokines and immunity in multiple sclerosis: The dual signal hypothesis. J Neuroimmunol 2000; 109(1): 3–9.
Matute C, et al. The link between excitotoxic oligodendroglial death and demyelinating diseases. Trends Neurosci 2001; 24(4): 224–30.
Medana I, et al. Transection of major histocompatibility complex class I-induced neurites by cytotoxic T lymphocytes. Am J Pathol 2001; 159(3): 809–15.
Merkler D, et al. Differential macrophage/microglia activation in neocortical EAE lesions in the marmoset monkey. Brain Pathol 2006; 16(2): 117–23.
Mew I, et al. Oligodendrocyte and axon pathology in clinically silent multiple sclerosis lesions. Mult Scler 1998; 4(2): 55–62.
Moalem G, et al. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med 1999; 5(1): 49–55.
Moalem G, et al. Production of neurotrophins by activated T cells: Implications for neuroprotective autoimmunity. J Autoimmun 2000; 15(3): 331–45.
Nedergaard M, et al. Beyond the role of glutamate as a neurotransmitter. Nat Rev Neurosci 2002; 3(9): 748–55.
Neumann H, et al. Cytotoxic T lymphocytes in autoimmune and degenerative CNS diseases. Trends Neurosci 2002; 25(6): 313–9.
Nitsch R, et al. Direct impact of T cells on neurons revealed by two-photon microscopy in living brain tissue. J Neurosci 2004; 24(10): 2458–64.
Olsson T, et al. Antimyelin basic protein and antimyelin antibody-producing cells in multiple sclerosis. Ann Neurol 1990; 27(2): 132–6.
O’Connor KC, et al. Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein. J Immunol 2005; 175(3): 1974–82.
Oleszak EL, et al. Inducible nitric oxide synthase and nitrotyrosine are found in monocytes/macrophages and/or astrocytes in acute, but not in chronic multiple sclerosis. Clin Diagn Lab Immunol 1998; 5: 438–45.
Ota K, et al. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 1990; 346(6280): 183–7.
Ozawa K, et al. Patterns of oligodendroglia pathology in multiple sclerosis. Brain 1994; 117: 1311–22.
Panitch HS, et al. Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet 1987a; 1: 893–5.
Panitch HS, et al. Treatment of multiple sclerosis with gamma interferon: Exacerbations associated with activation of the immune system. Neurology 1987b; 37: 1097–102.
Patrikios P et al. Remyelination is extensive in a subset of multiple sclerosis patients. Brain 2006; 129(12): 3165–72.
Peter H, et al. Matrix metalloproteinase-9 facilitates remyelination in part by processing the inhibitory NG2 proteoglycan. J Neurosci 2003; 23(35): 11127–35.
Peterson JW, et al. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 2001; 50(3): 389–400.
Peterson JW, rapp BD. Neuropathobiology of multiple sclerosis. Neurol Clin 2005; 23(1): 107–29.
Pette M, et al. Myelin basic protein-specific T lymphocyte lines from MS patients and healthy individuals. Neurology 1990; 40(11): 1770–6.
Piddlesden S, et al. The demyelinating potential of antibodies to myelin oligodendrocyte glycoprotein is related to their ability to fix complement. Am J Pathol 1993; 143(2): 555–64.
Pitt D, et al. Glutamate uptake by oligodendrocytes: Implications for excitotoxicity in multiple sclerosis. Neurology 2003; 61(8): 1113–20.
Pittock SJ, et al. Clinical course, pathological correlations, and outcome of biopsy proved inflammatory demyelinating disease. J Neurol Neurosurg Psychiatry 2005; 76(12): 1693–7.
Plumb J, et al. Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis. Brain Pathol 2002; 12(2): 154–69.
Pomeroy I, et al. Demyelinated neocortical lesions in marmoset autoimmune encephalomyelitis mimic those in multiple sclerosis. Brain 2005; 128(11): 2713–21.
Prineas JW, et al. Multiple sclerosis. Pathology of recurrent lesions. Brain 1993; 116(3): 681–93.
Prineas JW, et al. Immunopathology of secondary-progressive multiple sclerosis. Ann Neurol 2001; 50(5): 646–5.
Proescholdt MA, et al. Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats. J Neuropathol Exp Neurol 2002; 61: 914–25.
Raff M, et al. Axonal self-destruction and neurodegeneration. Science 2002; 296(5569): 868–71.
Ransohoff RM, et al. Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol 2003; 3(7): 569–81.
Redford EJ, et al. Nitric oxide donors reversibly block axonal conduction: demyelinated axons are especially susceptible. Brain 1997; 120(12): 2149–57.
Reindl M, et al. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 1999; 122(11): 2047–56.
Rodriguez M. Virus-induced demyelination in mice: “Dying back” of oligodendrocytes. Mayo Clin Proc 1985; 60: 433–8.
Rodriguez M, Scheithauer B. Ultrastructure of multiple sclerosis. Ultrastruct Pathol 1994; 18(1–2): 3–13.
Roemer S, et al. Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis. Brain 2007; 130(5): 1194–205.
Rostagno A, et al. Complement activation in chromosome 13 dementias. Similarities with Alzheimer’s disease. J Biol Chem 2002; 277(51): 49782–90.
Rovaris M, et al. Correlation between MRI and short-term clinical activity in multiple sclerosis: Comparison between standard- and triple-dose Gd-enhanced MRI. Eur Neurol 1999; 41(3): 123–7.
Rovaris M, et al. Secondary progressive multiple sclerosis: current knowledge and future challenges. Lancet Neurol 2006; 5(4): 343–54.
Sadatipour BT, et al. Increased circulating antiganglioside antibodies in primary and secondary progressive multiple sclerosis. Ann Neurol 1998; 44: 980–3.
Saoudi A, et al. Prevention of experimental allergic encephalomyelitis in rats by targeting autoantigen to B cells: Evidence that the protective mechanism depends on changes in the cytokine response and migratory properties of the autoantigen-specific T cells. J Exp Med 1995; 182(2): 335–44.
Schwab C, McGeer PL. Complement activated C4d immunoreactive oligodendrocytes delineate small cortical plaques in multiple sclerosis. Exp Neurol 2002; 174(1): 81–8.
Schwartz M, et al. Microglial phenotype: Is the commitment reversible? Trends Neurosci 2006; 29(2): 68–74.
Simpson J, et al. Expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue. J Neuroimmunol 2000; 108 (1–2): 192–200.
Serafini B, et al. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 2004; 14(2): 164–74.
Sharp FR, Bernaudin M. HIF1 and oxygen sensing in the brain. Nat Rev Neurosci 2004; 5(6): 437–48.
Skou JC. Nobel Lecture. The identification of the sodium pump. Biosci Rep 1998; 18(4): 155–69.
Skulina C, et al. Multiple sclerosis: Brain-infiltrating CD8+ T cells persist as clonal expansions in the cerebrospinal fluid and blood. Proc Natl Acad Sci USA 2004; 101 (8): 2428–33.
Smith KJ, et al. Electrically active axons degenerate when exposed to nitric oxide. Ann Neurol 2001; 49(4): 470–6.
Smith KJ, et al. The role of nitric oxide in multiple sclerosis. Lancet Neurol 2002; 1(4): 232–41.
Sorensen TL, et al. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J Clin Invest 1999; 103(6): 807–15.
Stadelmann C, et al. BDNF and gp145trkB in multiple sclerosis brain lesions: Neuroprotective interactions between immune and neuronal cells? Brain 2002; 125(1): 75–85.
Stadelmann C, et al. Tissue preconditioning may explain concentric lesions in Balo’s type of multiple sclerosis. Brain 2005; 128(5): 979–87.
Steinman L. Multiple sclerosis: A coordinated immunological attack against myelin in the central nervous system. Cell 1996; 85(3): 299–302.
Storch MK, et al. Multiple sclerosis: In situ evidence for antibody- and complement-mediated demyelination. Ann Neurol 1998a; 43(4): 465–71.
Storch MK, et al. Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology. Brain Pathol 1998b; 8(4): 681–94.
Streit W. Microglial senescence: Does the brain’s immune system have an expiration date? Trends Neurosci 2006; 29(9): 506–10.
Stys PK, et al. Axonal degeneration in multiple sclerosis: Is it time for neuroprotective strategies? Ann Neurol 2004; 55(5): 601–3.
Sun J, et al. T and B cell responses to myelin-oligodendrocyte glycoprotein in multiple sclerosis. J Immunol 1991; 146(5): 1490–5.
Tavolato BF. Immunoglobulin G distribution in multiple sclerosis brain. An immunofluorescence study. Neurol Sci 1975; 24(1): 1–11.
The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. TNF neutralization in MS: Results of a randomized, placebo-controlled multicenter study, 1998.
Trapp BD, et al. Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998; 338(5): 278–85.
Trebst C, et al. CCR1+/CCR5+ mononuclear phagocytes accumulate in the central nervous system of patients with multiple sclerosis. Am J Pathol 2001; 159(5): 1701–10.
Trebst C, et al. Chemokine receptors on infiltrating leucocytes in inflammatory pathologies of the central nervous system (CNS). Neuropathol Appl Neurobiol 2003; 29(6): 584–95.
Urich E, et al. Autoantibody-mediated demyelination depends on complement activation but not activatory Fc-receptors. Proc Natl Acad Sci USA 2006; 103(49): 18697–702.
Van Horssen J, et al. Matrix metalloproteinase-19 is highly expressed in active multiple sclerosis lesions. Neuropathol Appl Neurobiol 2006; 32(6): 585–93.
van Walderveen MA, et al. Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis. Neurology 1998; 50: 1282–8.
Vass K, et al. Localization of 70-kDa stress protein induction in gerbil brain after ischemia. Acta Neuropathol (Berl) 1988; 77(2): 128–35.
Vercellino M, et al. Grey matter pathology in multiple sclerosis. J Neuropathol Exp Neurol 2005; 64(12): 1101–7.
Vos CM, et al. Matrix metalloproteinase-12 is expressed in phagocytotic macrophages in active multiple sclerosis lesions. J Neuroimmunol 2003; 138(1–2): 106–14.
Warrington AE, et al. Human monoclonal antibodies reactive to oligodendrocytes promote remyelination in a model of multiple sclerosis. Proc Natl Acad Sci USA 2000; 97(12): 6820–5.
Washington R, et al. Expression of immunologically relevant endothelial cell activation antigens on isolated central nervous system microvessels from patients with multiple sclerosis. Ann Neurol 1994; 35: 89–97.
Waxman SG. Ions, energy and axonal injury: Towards a molecular neurology of multiple sclerosis. Trends Mol Med 2006a; 12(5): 192–5.
Waxman SG. Axonal conduction and injury in multiple sclerosis: The role of sodium channels. Nat Rev Neurosci 2006b; 7(12): 932–41.
Wegner C, et al. Neocortical neuronal, synaptic, and glial loss in multiple sclerosis. Neurology 2006; 67(6): 960–7.
Werner P, et al. Multiple sclerosis: Altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage. Ann Neurol 2001; 50(2): 169–80.
Wolswijk G, et al. Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells. J Neuroscience 1998; 18(2): 601–9.
Xiao BG, et al. Antibodies to myelin-oligodendrocyte glycoprotein in cerebrospinal fluid from patients with multiple sclerosis and controls. J Neuroimmunol 1991; 31(2): 91–6.
Yamashita T, et al. Changes in nitrite and nitrate (NO2/NO3) levels in cerebrospinal fluid of patients with multiple sclerosis. J Neurol Sci 1997; 153(1): 32–4.
Yasojima K, et al. Up-regulated production and activation of the complement system in Alzheimer’s disease brain. Am J Pathol 1999; 154(3): 927–36.
Yednock TA, et al. Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 1992; 356(6364): 63–6.
Zhou D, et al. Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein in multiple sclerosis. Proc Natl Acad Sci USA 2006; 103(50): 19057–62.