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Neuroinflammation in Neurological Disorders

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Neuron-Glia Interaction in Neuroinflammation

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 7))

Abstract

Neuroglial inflammation is a pathological hallmark of neuroimmunological disorders, such as multiple sclerosis, as well as neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease. Activated microglia and reactive astroglia accompany the loss of neurons and myelin in these conditions. Both microglia and astroglia can exert neuroprotective and neurotoxic functions, which are stage-dependent. Both cell types can switch from an anti-inflammatory/neuroprotective to a proinflammatory/neurotoxic phenotype according to the surrounding environmental stimuli. Deciphering glial dual actions may provide insights for the management of neuroglial inflammation and the future development of new drugs targeting glia in neuroimmunological and neurodegenerative diseases.

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References

  • Alexianu ME, Kozovska M, Appel SH (2001) Immune reactivity in a mouse model of familial ALS correlates with disease progression. Neurology 57:1282–1289

    PubMed  CAS  Google Scholar 

  • Allaman I, Bélanger M, Magistretti PJ (2011) Astrocyte-neuron metabolic relationships: for better and for worse. Trends Neurosci 34:76–87

    PubMed  CAS  Google Scholar 

  • Almer G, Guegan C, Teismann P et al (2001) Increased expression of the pro-inflammatory enzyme cyclooxygenase-2 in amyotrophic lateral sclerosis. Ann Neurol 49:176–185

    PubMed  CAS  Google Scholar 

  • Antony JM, van Marle G, Opii W et al (2004) Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination. Nat Neurosci 7:1088–1095

    PubMed  CAS  Google Scholar 

  • Appel SH, Engelhardt JI, Henkel JS et al (2008) Hematopoietic stem cell transplantation in patients with sporadic amyotrophic lateral sclerosis. Neurology 71:1326–1334

    PubMed  CAS  Google Scholar 

  • Azzouz M, Ralph GS, Storkebaum E et al (2004) VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model. Nature 429:413–417

    PubMed  CAS  Google Scholar 

  • Babbe H, Roers A, Waisman A et al (2000) 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 192:393–404

    PubMed  CAS  Google Scholar 

  • Banerjee R, Mosley RL, Reynolds AD et al (2008) Adaptive immune neuroprotection in G93A-SOD1 amyotrophic lateral sclerosis mice. PLoS One 3:e2740

    PubMed  Google Scholar 

  • Barnett MH, Prineas JW (2004) Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol 55:458–468

    PubMed  Google Scholar 

  • Bechmann I, Mor G, Nilsen J et al (1999) FasL (CD95L, Apo1L) is expressed in the normal rat and human brain: evidence for the existence of an immunological brain barrier. Glia 27:62–74

    PubMed  CAS  Google Scholar 

  • Bechmann I, Steiner B, Gimsa U et al (2002) Astrocyte-induced T cell elimination is CD95 ligand dependent. J Neuroimmunol 132:60–65

    PubMed  CAS  Google Scholar 

  • Bechmann I, Galea I, Perry VH (2007) What is the blood-brain barrier (not)? Trends Immunol 28:5–11

    PubMed  CAS  Google Scholar 

  • Beers DR, Henkel JS, Zhao W, Wang J, Appel SH (2008) CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc Natl Acad Sci U S A 105:15558–15563

    PubMed  CAS  Google Scholar 

  • Beers DR, Henkel JS, Zhao W et al (2011) Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain 134:1293–1314

    PubMed  Google Scholar 

  • Benarroch EE (2009) Oligodendrocytes. Susceptibility to injury and involvement in neurologic disease. Neurology 72:1779–1785

    PubMed  Google Scholar 

  • Bjartmar C, Kidd G, Mörk S, Rudick R, Trapp BD (2000) Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 48:893–901

    PubMed  CAS  Google Scholar 

  • Bö L, Vedeler CA, Nyland H, Trapp BD, Mörk SJ (2003) Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration. Mult Scler 9:323–331

    PubMed  Google Scholar 

  • Boillée S, Yamanaka K, Lobsiger CS et al (2006) Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312:1389–1392

    PubMed  Google Scholar 

  • Bonati U, Fisniku LK, Altmann DR et al (2011) Cervical cord and brain grey matter atrophy independently associate with long-term MS disability. J Neurol Neurosurg Psychiatry 82:471–472

    PubMed  CAS  Google Scholar 

  • Boor PK, de Groot K, Waisfisz Q et al (2005) MLC1: a novel protein in distal astroglial processes. J Neuropathol Exp Neurol 64:412–419

    PubMed  CAS  Google Scholar 

  • Booss J, Esiri MM, Tourtellotte WW, Mason DY (1983) Immunohistological analysis of T lymphocyte subsets in the central nervous system in chronic progressive multiple sclerosis. J Neurol Sci 62:219–232

    PubMed  CAS  Google Scholar 

  • Brand-Schieber E, Werner P, Iacobas DA et al (2005) Connexin43, the major gap junction protein of astrocytes, is down-regulated in inflamed white matter in an animal model of multiple sclerosis. J Neurosci Res 80:798–808

    PubMed  CAS  Google Scholar 

  • Breij EC, Brink BP, Veerhuis R et al (2008) Homogeneity of active demyelinating lesions in established multiple sclerosis. Ann Neurol 63:16–25

    PubMed  CAS  Google Scholar 

  • Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A (2001) Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet 27:117–120

    PubMed  CAS  Google Scholar 

  • Brilot F, Dale RC, Selter RC et al (2009) Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease. Ann Neurol 66:833–842

    PubMed  CAS  Google Scholar 

  • Calabrese M, Filippi M, Gallo P (2010) Cortical lesions in multiple sclerosis. Nat Rev Neurol 6:438–444

    PubMed  Google Scholar 

  • Campbell GR, Ziabreva I, Reeve AK et al (2011) Mitochondrial DNA deletions and neurodegeneration in multiple sclerosis. Ann Neurol 69:481–492

    PubMed  CAS  Google Scholar 

  • Cardona AE, Pioro EP, Sasse ME et al (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9:917–924

    PubMed  CAS  Google Scholar 

  • Chang A, Nishiyama A, Peterson J, Prineas J, Trapp BD (2000) NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions. J Neurosci 20:6404–6412

    PubMed  CAS  Google Scholar 

  • Chang A, Tourtellotte WW, Rudick R, Trapp BD (2002) Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med 346:165–173

    PubMed  Google Scholar 

  • Charles P, Reynolds R, Seilhean D et al (2002) Re-expression of PSA-NCAM by demyelinated axons: an inhibitor of remyelination in multiple sclerosis? Brain 125:1972–1979

    PubMed  Google Scholar 

  • Chastain EM, Duncan DS, Rodgers JM, Miller SD (1812) The role of antigen presenting cells in multiple sclerosis. Biochim Biophys Acta 2011:265–274

    Google Scholar 

  • Chiu AY, Zhai P, Dal Canto MC, Peters TM, Kwon YW, Prattis SM, Gurney ME (1995) Age-dependent penetrance of disease in a transgenic mouse model of familial amyotrophic lateral sclerosis. Mol Cell Neurosci 6:349–362

    PubMed  CAS  Google Scholar 

  • Chiu IM, Chen A, Zheng Y et al (2008) T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS. Proc Natl Acad Sci U S A 105:17913–17918

    PubMed  CAS  Google Scholar 

  • Clement AM, Nguyen MD, Roberts EA et al (2003) Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science 302:113–117

    PubMed  CAS  Google Scholar 

  • Coisne C, Mao W, Engelhardt B (2009) Cutting edge: natalizumab blocks adhesion but not initial contact of human T cells to the blood-brain barrier in vivo in an animal model of multiple sclerosis. J Immunol 182:5909–5913

    PubMed  CAS  Google Scholar 

  • Confavreux C, Vukusic S (2006) Age at disability milestones in multiple sclerosis. Brain 129:595–605

    PubMed  Google Scholar 

  • Confavreux C, Vukusic S, Moreau T, Adeleine P (2000) Relapses and progression of disability in multiple sclerosis. N Engl J Med 343:1430–1438

    PubMed  CAS  Google Scholar 

  • Derfuss T, Parikh K, Velhin S et al (2009) Contctin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals. Proc Natl Acad Sci U S A 106:8302–8307

    PubMed  CAS  Google Scholar 

  • Desmazières A, Sol-Foulon N, Lubetzki C (2012) Changes at the nodal and perinodal axonal domains: a basis for multiple sclerosis pathology? Mult Scler 18:133–137

    PubMed  Google Scholar 

  • Dong Y, Benveniste EN (2001) Immune function of astrocytes. Glia 36:180–190

    PubMed  CAS  Google Scholar 

  • Drachman DB, Frank K, Dykes-Hoberg M et al (2002) Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALS. Ann Neurol 52:771–778

    PubMed  CAS  Google Scholar 

  • Dutta R, McDonough J, Yin X et al (2006) Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann Neurol 59:478–489

    PubMed  CAS  Google Scholar 

  • Dutta R, Chang A, Doud MK et al (2011) Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients. Ann Neurol 69:445–454

    PubMed  CAS  Google Scholar 

  • Engelhardt B (2010) T cell migration into the central nervous system during health and disease: different molecular keys allow access to different central nervous system compartments. Clin Exp Neuroimmunol 1:79–93

    CAS  Google Scholar 

  • Engelhardt JI, Tajti J, Appel SH (1993) Lymphocytic infiltrates in the spinal cord in amyotrophic lateral sclerosis. Arch Neurol 50:30–36

    PubMed  CAS  Google Scholar 

  • Ezan P, André P, Cisternino S et al (2012) Deletion of astroglial connexins weakens the blood-brain barrier. J Cereb Blood Flow Metab 32:1457–1467

    PubMed  CAS  Google Scholar 

  • Ferguson B, Matyszak MK, Esiri MM, Perry VH (1997) Axonal damage in acute multiple sclerosis lesions. Brain 120:393–399

    PubMed  Google Scholar 

  • Fischer LR, Culver DG, Tennant P et al (2004) Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp Neurol 185:232–240

    PubMed  Google Scholar 

  • Fisher E, Lee JC, Nakamura K, Rudick RA (2008) Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol 64:255–265

    PubMed  Google Scholar 

  • Fisniku LK, Chard DT, Jackson JS et al (2008) Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol 64:247–254

    PubMed  Google Scholar 

  • Friese MA, Fugger L (2009) Pathogenic CD8(+) T cells in multiple sclerosis. Ann Neurol 66:132–141

    PubMed  CAS  Google Scholar 

  • Frischer JM, Bramow S, Dal-Bianco A et al (2009) The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain 132:1175–1189

    PubMed  Google Scholar 

  • Gallo V, Armstrong RC (2008) Myelin repair strategies: a cellular view. Curr Opin Neurol 21:278–283

    PubMed  Google Scholar 

  • Geurts JJ, Pouwels PJ, Uitdehaag BM, Polman CH, Barkhof F, Castelijns JA (2005) Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging. Radiology 236:254–260

    PubMed  Google Scholar 

  • Gimenez MA, Sim JE, Russell JH (2004) TNFR1-dependent VCAM-1 expression by astrocytes exposes the CNS to destructive inflammation. J Neuroimmunol 151:116–125

    PubMed  CAS  Google Scholar 

  • Gowing G, Dequen F, Soucy G, Julien JP (2006) Absence of tumor necrosis factor-alpha does not affect motor neuron disease caused by superoxide dismutase I mutations. J Neurosci 26:11397–11402

    PubMed  CAS  Google Scholar 

  • Gowing G, Philips T, Van Wijmeersch B et al (2008) Ablation of proliferating microglia does not affect motor neuron degeneration in amyotrophic lateral sclerosis caused by mutant superoxide dismutase. J Neurosci 28:10234–10244

    PubMed  CAS  Google Scholar 

  • Hauser SL, Waubant E, Arnold DL et al (2008) B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 358:676–688

    PubMed  CAS  Google Scholar 

  • Hayashi S, Sakurai A, Amari M, Okamoto K (2001) Pathological study of the diffuse myelin pallor in the anterolateral columns of the spinal cord in amyotrophic lateral sclerosis. J Neurol Sci 188:3–7

    PubMed  CAS  Google Scholar 

  • Henkel JS, Engelhardt JI, Siklos L et al (2004) Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Ann Neurol 55:221–235

    PubMed  CAS  Google Scholar 

  • Henkel JS, Beers DR, Siklos L, Apple SH (2005) The chemokine MCP-1 and the dendritic and myeloid cells it attracts are increased in the mSOD1 mouse model of ALS. Mol Cell Neurosci 31:427–437

    PubMed  Google Scholar 

  • Howland DS, Liu J, She Y et al (2002) Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc Natl Acad Sci U S A 99:1604–1609

    PubMed  CAS  Google Scholar 

  • Ince PG, Highley JR, Kirby J, Wharton SB, Takahashi H, Strong MJ, Shaw PJ (2011) Molecular pathology and genetic advances in amyotrophic lateral sclerosis: an emerging molecular pathway and the significance of glial pathology. Acta Neuropathol 122:657–671

    PubMed  CAS  Google Scholar 

  • Ishizu T, Osoegawa M, Mei FJ et al (2005) Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis. Brain 128:988–1002

    PubMed  Google Scholar 

  • Janzer RC, Raff MC (1987) Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 325:253–257

    PubMed  CAS  Google Scholar 

  • Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA (2002) Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci U S A 99:11946–11950

    PubMed  CAS  Google Scholar 

  • John GR, Shankar SL, Shafit-Zagardo B et al (2002) Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nat Med 8:1115–1121

    PubMed  CAS  Google Scholar 

  • Kaspar BK, Llado J, Sherkat N, Rothstein JD, Gage FH (2003) Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model. Science 301:839–842

    PubMed  CAS  Google Scholar 

  • Kawajiri M, Mogi M, Osoegawa M et al (2008) Reduction of angiotensin II in the cerebrospinal fluid of patients with multiple sclerosis. Mult Scler 14:557–560

    PubMed  CAS  Google Scholar 

  • Kawajiri M, Mogi M, Higaki N et al (2009) Angiotensin-converting enzyme (ACE) and ACE2 levels in the cerebrospinal fluid of patients with multiple sclerosis. Mult Scler 15:262–265

    PubMed  CAS  Google Scholar 

  • Kawamata T, Akiyama H, Yamada T, McGeer PL (1992) Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am J Pathol 140:691–707

    PubMed  CAS  Google Scholar 

  • Kawamura MF, Yamasaki R, Kawamura N et al (2012) Impaired recruitment of neuroprotective microglia and T cells during acute neuronal injury coincides with increased neuronal vulnerability in an amyotrophic lateral sclerosis model. Exp Neurol 234:437–445

    PubMed  CAS  Google Scholar 

  • Kondo T, Takahashi K, Kohara N et al (2002) Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms. Neurology 59:1105–1107

    PubMed  CAS  Google Scholar 

  • Kooi EJ, Geurts JJ, van Horssen J, Bø L, van der Valk P (2009) Meningeal inflammation is not associated with cortical demyelination in chronic multiple sclerosis. J Neuropathol Exp Neurol 68:1021–1028

    PubMed  CAS  Google Scholar 

  • Kornek B, Lassmann H (1999) Axonal pathology in multiple sclerosis. A historical note. Brain Pathol 9:651–656

    PubMed  CAS  Google Scholar 

  • Kotter MR, Li WW, Zhao C, Franklin RJ (2006) Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation. J Neurosci 26:328–332

    PubMed  CAS  Google Scholar 

  • Kremenchutzky M, Rice GP, Baskerville J, Wingerchuk DM, Ebers GC (2006) The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease. Brain 129:584–594

    PubMed  CAS  Google Scholar 

  • Kroenke MA, Carlson TJ, Andjelkovic AV, Segal BM (2008) IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition. J Exp Med 205:1535–1541

    PubMed  CAS  Google Scholar 

  • Kuhlmann T, Lingfeld G, Bitsch A, Schuchardt J, Brück W (2002) Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain 125:2202–2212

    PubMed  Google Scholar 

  • Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452

    PubMed  CAS  Google Scholar 

  • Kushner PD, Stephenson DT, Wright S (1991) Reactive astrogliosis is widespread in the subcortical white matter of amyotrophic lateral sclerosis brain. J Neuropathol Exp Neurol 50:63–277

    Google Scholar 

  • Kutzelnigg A, Lucchinetti CF, Stadelmann C et al (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128:2705–2712

    PubMed  Google Scholar 

  • Lassmann H, Raine CS, Antel J, Prineas JW (1998) Immunopathology of multiple sclerosis: report on an international meeting held at the institute of neurology of the University of Vienna. J Neuroimmunol 86:213–217

    PubMed  CAS  Google Scholar 

  • Leegwater PA, Yuan BQ, van der Steen J et al (2001) Mutations of MLC1 (KIAA0027) encoding a putative membrane protein cause megalencepahlic leukoencephalopathy with subcortical cysts. Am J Hum Genet 68:831–838

    PubMed  CAS  Google Scholar 

  • Lennon VA, Wingerchuk DM, Kryzer TJ et al (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364:2106–2112

    PubMed  CAS  Google Scholar 

  • Lennon VA, Kryzer TJ, Pittock SJ et al (2005) IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202:473–477

    PubMed  CAS  Google Scholar 

  • Li R, Johnson AB, Salomons G et al (2005) Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease. Ann Neurol 57:310–326

    PubMed  Google Scholar 

  • Liem RK, Messing A (2009) Dysfunctions of neuronal and glial intermediate filaments in disease. J Clin Invest 119:1814–1824

    PubMed  CAS  Google Scholar 

  • Lucchinetti C (2007) Multiple sclerosis pathology during early and late disease phases: pathogenic and clinical relevance. In: Zhang J (ed) Immune regulation and immunotherapy in autoimmune disease. Springer, New York, pp 214–264

    Google Scholar 

  • Lucchinetti C, Brück 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

    PubMed  CAS  Google Scholar 

  • Lutz SE, Zhao Y, Gulinello M, Lee SC, Raine CS, Brosnan CF (2009) Deletion of astrocyte connexins 43 and 30 leads to a dysmyelinating phenotype and hippocampal CA1 vacuolation. J Neurosci 29:7743–7752

    PubMed  CAS  Google Scholar 

  • Magliozzi R, Howell O, Vora A et al (2007) Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 130:1089–1104

    PubMed  Google Scholar 

  • Magliozzi R, Howell OW, Reeves C et al (2010) A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol 68:477–493

    PubMed  CAS  Google Scholar 

  • Magnotti LM, Goodenough DA, Paul DL (2011) Deletion of oligodendrocyte Cx32 and astrocyte Cx43 causes white matter vacuolation, astrocyte loss and early mortality. Glia 59:1064–1074

    PubMed  Google Scholar 

  • Mahad DJ, Ransohoff RM (2003) The role of MCP-1 (CCL2) and CCR2 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Semin Immunol 15:23–32

    PubMed  CAS  Google Scholar 

  • Mahad DJ, Howell SJ, Woodroofe MN (2002) Expression of chemokines in the CSF and correlation with clinical disease activity in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 72:498–502

    PubMed  CAS  Google Scholar 

  • Markoullis K, Sargiannidou I, Gardner C, Hadjisavvas A, Reynolds R, Kleopa KA (2012) Disruption of oligodendrocyte gap junctions in experimental autoimmune encephalomyelitis. Glia 60:1053–1066

    PubMed  Google Scholar 

  • Markovic M, Miljkovic D, Momcilovic M et al (2009) Strain difference in susceptibility to experimental autoimmune encephalomyelitis in rats correlates with T(H)1 and T(H)17-inducing cytokine profiles. Mol Immunol 47:141–146

    PubMed  CAS  Google Scholar 

  • Masaki K, Suzuki SO, Matsushita T et al (2012) Extensive loss of connexins in Baló’s disease: evidence for an auto-antibody-independent astrocytopathy via impaired astrocyte-oligodendrocyte/myelin interaction. Acta Neuropathol 123:887–900

    PubMed  Google Scholar 

  • Masaki K, Suzuki SO, Matsushita T et al (2013) Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica. PLoS One (in press)

    Google Scholar 

  • Mathey EK, Derfuss T, Storch MK et al (2007) Neurofascin as a novel target for autoantibody-mediated axonal injury. J Exp Med 204:2363–2372

    PubMed  CAS  Google Scholar 

  • Matsuoka T, Suzuki SO, Suenaga T, Iwaki T, Kira J (2011) Reappraisal of aquaporin-4 astrocytopathy in Asian neuromyelitis optica and multiple sclerosis patients. Brain Pathol 11:516–532

    Google Scholar 

  • Matsushita T, Isobe N, Kawajiri M et al (2010) CSF angiotensin II and angiotensin-converting enzyme levels in anti-aquaporin-4 autoimmunity. J Neurol Sci 291:37–43

    PubMed  CAS  Google Scholar 

  • Matsushita T, Tateishi T, Isobe N, Yonekawa T, Yamasaki R, Murai H, Kira J (2013) Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis. PLoS One 8(4):e61835

    PubMed  CAS  Google Scholar 

  • Meinl E, Krumbholz M, Hohlfeld R (2006) B lineage cells in the inflammatory central nervous system environment: migration, maintenance, local antibody production, and therapeutic modulation. Ann Neurol 59:880–892

    PubMed  CAS  Google Scholar 

  • Meissner F, Molawi K, Zychlinsky A (2010) Mutant superoxide dismutase 1-induced IL-1beta accelerates ALS pathogenesis. Proc Natl Acad Sci U S A 107:13046–13050

    PubMed  CAS  Google Scholar 

  • Menichella DM, Goodenough DA, Sirkowski E, Scherer SS, Paul DL (2003) Connexins are critical for normal myelination in the CNS. J Neurosci 23:5963–5973

    PubMed  CAS  Google Scholar 

  • Mi S, Miller RH, Lee X et al (2005) LINGO-1 negatively regulates myelination by oligodendrocytes. Nat Neurosci 8:745–751

    PubMed  CAS  Google Scholar 

  • Miljković D, Timotijević G, Mostarica Stojković M (2011) Astrocytes in the tempest of multiple sclerosis. FEBS Lett 585:3781–3788

    PubMed  Google Scholar 

  • Miller RH, Raff MC (1984) Fibrous and protoplasmic astrocytes are biochemically and developmentally distinct. J Neurosci 4:585–592

    PubMed  CAS  Google Scholar 

  • Mistry N, Dixon J, Tallantyre E et al (2013) Central veins in brain lesions visualized with high-field magnetic resonance imaging: a pathologically specific diagnostic biomarker for inflammatory demyelination in the brain. JAMA Neurol 70:1–6

    Google Scholar 

  • Mitchell RM, Freeman WM, Randazzo WT, Stephens HE, Beard JL, Simmons Z, Connor JR (2009) A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis. Neurology 72:14–19

    PubMed  CAS  Google Scholar 

  • Moore CS, Abdullah SL, Brown A, Arulpragasam A, Crocker SJ (2011) How factors secreted from astrocytes impact myelin repair. J Neurosci Res 89:13–21

    PubMed  CAS  Google Scholar 

  • Nagara Y, Tateishi T, Yamasaki R, et al (2013) Impaired cytoplasmic-nuclear transport of hypoxia-inducible factor-1α in amyotrophic lateral sclerosis. Brain Pathol. doi: 10.1111/bpa.12040. [Epub ahead of print]

  • Nagy D, Kato T, Kushner PD (1994) Reactive astrocytes are widespread in the cortical gray matter of amyotrophic lateral sclerosis. J Neurosci Res 38:336–347

    PubMed  CAS  Google Scholar 

  • Nakahara J, Kanekura K, Nawa M, Aiso S, Suzuki N (2009) Abnormal expression of TIP30 and arrested nucleocytoplasmic transport within oligodendrocyte precursor cells in multiple sclerosis. J Clin Invest 119:169–181

    PubMed  CAS  Google Scholar 

  • Nguyen MD, Julien JP, Rivest S (2001) Induction of proinflammatory molecules in mice with amyotrophic lateral sclerosis: no requirement for proapoptotic interleukin-1beta in neurodegeneration. Ann Neurol 50:630–639

    PubMed  CAS  Google Scholar 

  • Odoardi F, Sie C, Streyl K et al (2012) T cells become licensed in the lung to enter the central nervous system. Nature 488:675–679

    PubMed  CAS  Google Scholar 

  • Otero K, Turnbull IR, Poliani PL et al (2009) Macrophage colony-stimulating factor induces the proliferation and survival of macrophages via a pathway involving DAP12 and beta-catenin. Nat Immunol 10:734–743

    PubMed  CAS  Google Scholar 

  • Paloneva J, Kestilä M, Wu J et al (2000) Loss-of-function mutations in TYROBP (DAP12) results in a presenile dementia with bone cysts. Nat Genet 25:357–361

    PubMed  CAS  Google Scholar 

  • Paloneva J, Manninen T, Christman G et al (2002) Mutations in two genes encoding different subunits of a receptor signalling complex result in an identical disease phenotype. Am J Hum Genet 71:656–662

    PubMed  CAS  Google Scholar 

  • Patani R, Balaratnam M, Vora A, Reynolds R (2007) Remyelination can be extensive in multiple sclerosis despite a long disease course. Neuropathol Appl Neurobiol 33:277–287

    PubMed  CAS  Google Scholar 

  • Patrikios P, Stadelmann C, Kutzelnigg A et al (2006) Remyelination is extensive in a subset of multiple sclerosis patients. Brain 129:3165–3172

    PubMed  Google Scholar 

  • Pellkofer HL, Krumbholz M, Berthele A et al (2011) Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximab. Neurology 76:1310–1315

    PubMed  CAS  Google Scholar 

  • Peterson JW, Bö L, Mörk S, Chang A, Trapp BD (2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50:389–400

    PubMed  CAS  Google Scholar 

  • Philips T, Robberecht W (2011) Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol 10:253–263

    PubMed  CAS  Google Scholar 

  • Philips T, Bento-Abreu A, Nonneman A et al (2013) Oligodendrocyte dysfunction in the pathogenesis of amyotrophic lateral sclerosis. Brain 136:471–482

    PubMed  Google Scholar 

  • Pitt D, Nagelmeier IE, Wilson HC, Raine CS (2003) Glutamate uptake by oligodendrocytes: implications for excitotoxicity in multiple sclerosis. Neurology 61:1113–1120

    PubMed  CAS  Google Scholar 

  • Pompl PN, Ho L, Bianchi M, McManus T, Qin W, Pasinetti GM (2003) A therapeutic role for cyclooxygenase-2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis. FASEB J 17:725–727

    PubMed  CAS  Google Scholar 

  • Pramatarova A, Laganière J, Roussel J, Brisebois K, Rouleau GA (2001) Neuron-specific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor impairment. J Neurosci 21:3369–3374

    PubMed  CAS  Google Scholar 

  • Prineas JW, Barnard RO, Revesz T, Kwon EE, Sharer L, Cho ES (1993) Multiple sclerosis. Pathology of recurrent lesions. Brain 116:681–693

    PubMed  Google Scholar 

  • Quinlan RA, Brenner M, Goldman JE, Messing A (2007) GFAP and its role in Alexander disease. Exp Cell Res 313:2077–2087

    PubMed  CAS  Google Scholar 

  • Rademakers R, Baker M, Nicholson AM et al (2012) Mutations in colony stimulating factor 1 (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat Genet 44:200–205

    CAS  Google Scholar 

  • Ransohoff RM, Cardona AE (2010) The myeloid cells of the central nervous system parenchyma. Nature 468:253–262

    PubMed  CAS  Google Scholar 

  • Ransohoff RM, Engelhardt B (2012) The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol 12:623–635

    PubMed  CAS  Google Scholar 

  • Ratcliffe CF, Westenbroek RE, Curtis R, Catterall WA (2001) Sodium channel beta1 and beta3 subunits associate with neurofascin through their extracellular immunoglobulin-like domain. J Cell Biol 154:427–434

    PubMed  CAS  Google Scholar 

  • Reynolds R, Roncaroli F, Nicholas R, Radotra B, Gveric D, Howell O (2011) The neuropathological basis of clinical progression in multiple sclerosis. Acta Neuropathol 122:155–170

    PubMed  Google Scholar 

  • Rothstein JD, Martin LJ, Kuncl RW (1992) Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl J Med 326:1464–1468

    PubMed  CAS  Google Scholar 

  • Rothstein JD, Van Kammen M, Levey AI, Martin LJ, Kuncl RW (1995) Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol 38:73–84

    PubMed  CAS  Google Scholar 

  • Saha RN, Pahan K (2006) Regulation of inducible nitric oxide synthase gene in glial cells. Antioxid Redox Signal 8:929–947

    PubMed  CAS  Google Scholar 

  • Saiga T, Tateishi T, Torii T et al (2012) Inflammatory radiculoneuropathy in an ALS4 patient with a novel SETX mutation. J Neurol Neurosurg Psychiatry 83:763–764

    PubMed  Google Scholar 

  • Saikali P, Antel JP, Pittet CL, Newcombe J, Arbour N (2010) Contribution of astrocyte-derived IL-15 to CD8 T cell effector functions in multiple sclerosis. J Immunol 185:5693–5703

    PubMed  CAS  Google Scholar 

  • Saitoh B, Yamasaki R, Hayashi S et al (2013) A case of hereditary diffuse leukoencephalopathy with spheroids caused by a de novo mutation in CSFIR masquerading as primary progressive multiple sclerosis. Mult Scler (in press)

    Google Scholar 

  • Sasaki S, Warita H, Abe K, Iwata M (2001) Inducible nitric oxide synthase (iNOS) and nitrotyrosine immunoreactivity in the spinal cords of transgenic mice with a G93A mutant SOD1 gene. J Neuropathol Exp Neurol 60:839–846

    PubMed  CAS  Google Scholar 

  • Satoh J, Tabunoki H, Yamamura T, Arima K, Konno H (2007) TROY and LINGO-1 expression in astrocytes and macrophages/microglia in multiple sclerosis lesions. Neuropathol Appl Neurobiol 33:99–107

    PubMed  CAS  Google Scholar 

  • Sawaishi Y (2009) Review of Alexander disease: beyond the classical concept of leukodystrophy. Brain Dev 31:493–498

    PubMed  Google Scholar 

  • Schiffer D, Cordera S, Cavalla P, Migheli A (1996) Reactive astrogliosis of the spinal cord in amyotrophic lateral sclerosis. J Neurol Sci 139(suppl):27–33

    PubMed  Google Scholar 

  • Scott S, Kranz JE, Cole J et al (2008) Design, power, and interpretation of studies in the standard murine model of ALS. Amyotroph Lateral Scler 9:4–15

    PubMed  CAS  Google Scholar 

  • Sherman DL, Tait S, Melrose S et al (2005) Neurofascins are required to establish axonal domains for saltatory conduction. Neuron 48:737–742

    PubMed  CAS  Google Scholar 

  • Simard AR, Soulet D, Gowing G, Julien JP, Rivest S (2006) Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 16:489–502

    Google Scholar 

  • Skripuletz T, Hackstette D, Bauer K et al (2013) Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination. Brain 136:147–167

    PubMed  Google Scholar 

  • Srinivasan R, Sailasuta N, Hurd R, Nelson S, Pelletier D (2005) Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T. Brain 128:1016–1025

    PubMed  Google Scholar 

  • Srivastava R, Aslam M, Kalluri SR et al (2012) Potassium channel KIR4.1 as an immune target in multiple sclerosis. N Engl J Med 367:115–123

    PubMed  CAS  Google Scholar 

  • Stadelmann C, Wegner C, Brück W (2011) Inflammation, demyelination, and degeneration—recent insights from MS pathology. Biochim Biophys Acta 1812:275–282

    Google Scholar 

  • Stoffels JM, de Jonge JC, Stancic M et al (2013) Fibronectin aggregation in multiple sclerosis lesions impairs remyelination. Brain 136:116–131

    PubMed  Google Scholar 

  • Storkebaum E, Lambrechts D, Dewerchin M et al (2005) Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS. Nat Neurosci 8:85–92

    PubMed  CAS  Google Scholar 

  • Tanaka M, Kikuchi H, Ishizu T et al (2006) Intrathecal upregulation of granulocyte colony stimulating factor and its neuroprotective actions on motor neurons in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 65:816–825

    PubMed  CAS  Google Scholar 

  • Tanaka M, Matsushita T, Tateishi T et al (2008) Distinct CSF cytokine/chemokine profiles in atopic myelitis and other causes of myelitis. Neurology 71:974–981

    PubMed  CAS  Google Scholar 

  • Tateishi T, Yamasaki R, Tanaka M et al (2010) CSF chemokine alterations related to the clinical course of amyotrophic lateral sclerosis. J Neuroimmunol 222:76–81

    PubMed  CAS  Google Scholar 

  • Tolosa L, Mir M, Asensio VJ, Olmos G, Llado J (2008) Vascular endothelial growth factor protects spinal cord motoneurons against glutamate-induced excitotoxicity via phosphatidylinositol 3-kinase. J Neurochem 105:1080–1090

    PubMed  CAS  Google Scholar 

  • Tran EH, Hoekstra K, van Rooijen N, Dijkstra CD, Owens T (1998) Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice. J Immunol 161:3767–3775

    PubMed  CAS  Google Scholar 

  • Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278–285

    PubMed  CAS  Google Scholar 

  • Turner MR, Cagnin A, Turkheimer FE et al (2004) Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol Dis 15:601–609

    PubMed  CAS  Google Scholar 

  • van der Laan LJ, De Groot CJ, Elices MJ, Dijkstra CD (1997) Extracellular matrix proteins expressed by human adult astrocytes in vivo and in vitro: an astrocyte surface protein containing the CS1 domain contributes to binding of lymphoblasts. J Neurosci Res 50:539–548

    PubMed  Google Scholar 

  • van Horssen J, Bö L, Vos CM, Virtanen I, de Vries HE (2005) Basement membrane proteins in multiple sclerosis-associated inflammatory cuffs: potential role in influx and transport of leukocytes. J Neuropathol Exp Neurol 64:722–729

    PubMed  Google Scholar 

  • van Horssen J, Dijkstra CD, de Vries HE (2007) The extracellular matrix in multiple sclerosis pathology. J Neurochem 103:1293–1301

    PubMed  Google Scholar 

  • Vercellino M, Plano F, Votta B, Mutani R, Giordana MT, Cavalla P (2005) Grey matter pathology in multiple sclerosis. J Neuropathol Exp Neurol 64:1101–1107

    PubMed  Google Scholar 

  • Voskuhl RR, Peterson RS, Song B et al (2009) Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS. J Neurosci 29:11511–11522

    PubMed  CAS  Google Scholar 

  • Wang Y, Szretter KJ, Vermi W et al (2012) IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat Immunol 13:753–760

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Weydt P, Yuen EC, Ransom BR, Moller T (2004) Increased cytotoxic potential of microglia from ALS-transgenic mice. Glia 48:179–182

    PubMed  Google Scholar 

  • Xu J, Drew PD (2007) Peroxisome proliferator-activated receptor-gamma agonists suppress the production of IL-12 family cytokines by activated glia. J Immunol 178:1904–1913

    PubMed  CAS  Google Scholar 

  • Yamanaka K, Chun SJ, Boillée S et al (2008) Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci 11:251–253

    PubMed  CAS  Google Scholar 

  • Yamasaki R, Tanaka M, Fukunaga M et al (2010) Restoration of microglial function by granulocyte-colony stimulating factor in ALS model mice. J Neuroimmunol 229:51–62

    PubMed  CAS  Google Scholar 

  • Yamasaki R, Liu LP, Lin J, Ransohoff RM (2012) Role of CCR2 in immunobiology and neurobiology. Clin Exp Neuroimmunol 3:16–29

    CAS  Google Scholar 

  • Yang Y, Gozen O, Watkins A et al (2009) Presynaptic regulation of astroglial excitatory neurotransmitter transporter GLT1. Neuron 61:880–894

    PubMed  CAS  Google Scholar 

  • Zhu S, Stavrovskaya IG, Drozda M et al (2002) Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 417:74–78

    PubMed  CAS  Google Scholar 

  • Zimmermann DR, Dours-Zimmermann MT (2008) Extracellular matrix of the central nervous system: from neglect to challenge. Histochem Cell Biol 130:635–653

    PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by a Health and Labour Sciences Research Grant on Intractable Diseases from the Ministry of Health, Labour and Welfare, Japan, and a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Conflict of interest Dr. Kira is an advisory board member for Merck Serono and a consultant for Biogen Idec Japan. He has received payment for lectures from Bayer Schering Pharma, Cosmic Cooperation, and Biogen Idec Japan.

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  1. Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Jun-ichi Kira M.D., Ph.D.

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  1. Jun-ichi Kira M.D., Ph.D.
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Correspondence to Jun-ichi Kira M.D., Ph.D. .

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  1. Department of Neuroimmunology Research Inst. of Environmental Medicine, Nagoya University, Nagoya, Japan

    Akio Suzumura

  2. Div of Neurobiology & Neuroinformatics, National Inst of Physiological Science, Aichi, Japan

    Kazuhiro Ikenaka

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Kira, Ji. (2013). Neuroinflammation in Neurological Disorders. In: Suzumura, A., Ikenaka, K. (eds) Neuron-Glia Interaction in Neuroinflammation. Advances in Neurobiology, vol 7. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8313-7_2

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