Abstract
Astrocytes are the most abundant and heterogeneous type of glial cell in the Central Nervous System. In addition to their role maintaining physiological conditions stable in the CNS, they are recognized as early and highly active players in immune responses in the CNS, and their dysfunction is believed to contribute to neuroimmune disease.
Perhaps one of the most important discoveries in recent years has been the identification of IgG-NMO, a specific pathogenic antibody directed against water channel aquaporin-4 (AQP4). IgG-NMO has not only made neuromyelitis optica diagnosis easier but has allowed differential diagnoses to be established more clearly and lead to the design of better therapeutic alternatives. Likewise, a novel autoantibody directed against GFAP has been identified as biomarker of a relapsing autoimmune form of meningoencephalomyelitis, responsive to steroids, often associated with tumors. Similarly, in Rasmussen’s encephalitis, CD8+ T lymphocytes cause astrocyte apoptosis and loss in affected areas, altering normal neuron function. Reactive astrocytes also play an important role in different CNS infections, not only during acute phases of disease but also long term, and may condition the development of post-infectious sequelae. Finally, multiple mechanisms mediated by astrocytes are known to participate in both the genesis and the progression of MS and in processes of remyelination. Overall, these observations indicate astrocytes actively participate in both pathological and in repair mechanisms, observed in CNS neuroimmune diseases.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- AMPA:
-
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
- AQP4:
-
Aquaporin 4
- ATP:
-
Adenosine triphosphate
- B4GALT5:
-
4-Galactosyltransferase 5
- BAFF:
-
B-cell activating factor
- BBB:
-
Blood–brain barrier
- C1q:
-
Complement component subunit 1q
- CNS:
-
Central Nervous System
- CNTF:
-
Ciliary neurotrophic factor
- CSPGs:
-
Chondroitin sulfate proteoglycans
- Cx:
-
Connexin
- DAMPS:
-
Danger-associated molecules patterns
- EAAT2:
-
Excitatory amino acid transporter 2
- EAE:
-
Experimental autoimmune encephalomyelitis
- ECM:
-
Extracellular matrix
- EPH:
-
Ephrins
- Fas-L:
-
Fas ligand
- FGF:
-
Fibroblast growth factor
- FoxP3:
-
Forkhead box P3
- GAG:
-
Glycosaminoglycan
- GFAP:
-
Glial fibrillary acidic protein
- GLAST:
-
Glutamate/aspartate transporter
- GLT-1:
-
Glutamate transporter-1
- GluR3:
-
Glutamate receptor 3
- GM-CSF:
-
Granulocyte macrophage colony-stimulating factor
- GS:
-
Glutamine synthetase
- HMGB1:
-
High-mobility box-1
- ICAM 1:
-
Intercellular adhesion molecule 1
- IFNs:
-
Interferons
- iNOS:
-
Inducible nitric oxide synthase
- IRF-1:
-
Interferon regulatory factor 1
- ISGs:
-
Interferon-stimulated genes
- LacCer:
-
Lactosylceramide
- LFA-1:
-
Lymphocyte function-associated antigen
- LIF:
-
Leukemia inhibitory factor
- LPS:
-
Lipopolysaccharide
- M-CSF:
-
Macrophage colony-stimulating factor
- MMPs:
-
Matrix metalloproteinases
- NF-κB:
-
Nuclear factor kappa-light-chain-enhancer of activated B cells
- NG2:
-
Neuron-glial antigen 2
- NMDA:
-
N-methyl-D-aspartate
- NMO:
-
Neuromyelitis optica
- NMOSD:
-
Neuromyelitis optica spectrum disorders
- NO:
-
Nitric oxide
- ONOO−:
-
Peroxinitrate
- OPCs:
-
Oligodendrocyte progenitor cells
- PAMPs:
-
Pathogen-associated molecular patterns
- PRRs:
-
Pattern recognition receptors
- RAGE:
-
Receptor for advanced glycation end products
- RE:
-
Rasmussen’s encephalitis
- RLRs:
-
Retinoic acid-inducible gene-like receptors
- S100β:
-
S100 calcium-binding protein
- TGF:
-
Transforming growth factor
- Th:
-
T helper cell
- Tim-3:
-
T cell immunoglobulin and mucin domain 3
- TIMPs:
-
Tissue inhibitors of metalloproteinases
- TLR:
-
Toll-like receptor
- Tr1:
-
Type 1 regulatory T cells
- VCAM-1:
-
Vascular cell adhesion protein 1
- VLA-4:
-
Very late antigen 4
References
Banker GA. Trophic interactions between astroglial cells and hippocampal neurons in culture. Science. 1980;209(4458):809–10.
Kettenmann H, Verkhratsky A. Neuroglia: the 150 years after. Trends Neurosci. 2008;31(12):653–9. https://doi.org/10.1016/j.tins.2008.09.003.
Butt AM, Duncan A, Berry M. Astrocyte associations with nodes of Ranvier: ultrastructural analysis of HRP-filled astrocytes in the mouse optic nerve. J Neurocytol. 1994;23(8):486–99.
Bushong EA, Martone ME, Ellisman MH. Maturation of astrocyte morphology and the establishment of astrocyte domains during postnatal hippocampal development. Int J Dev Neurosci. 2004;22(2):73–86. https://doi.org/10.1016/j.ijdevneu.2003.12.008.
Witcher MR, Kirov SA, Harris KM. Plasticity of perisynaptic astroglia during synaptogenesis in the mature rat hippocampus. Glia. 2007;55(1):13–23. https://doi.org/10.1002/glia.20415.
Foo LC, Allen NJ, Bushong EA, Ventura PB, Chung WS, Zhou L, et al. Development of a method for the purification and culture of rodent astrocytes. Neuron. 2011;71(5):799–811. https://doi.org/10.1016/j.neuron.2011.07.022.
Farmer WT, Murai K. Resolving astrocyte heterogeneity in the CNS. Front Cell Neurosci. 2017;11:300. https://doi.org/10.3389/fncel.2017.00300.
Wolburg H, Noell S, Mack A, Wolburg-Buchholz K, Fallier-Becker P. Brain endothelial cells and the glio-vascular complex. Cell Tissue Res. 2009;335(1):75–96. https://doi.org/10.1007/s00441-008-0658-9.
Milosevic A, Goldman JE. Potential of progenitors from postnatal cerebellar neuroepithelium and white matter: lineage specified vs. multipotent fate. Mol Cell Neurosci. 2004;26(2):342–53. https://doi.org/10.1016/j.mcn.2004.02.008.
Wang DD, Bordey A. The astrocyte odyssey. Prog Neurobiol. 2008;86(4):342–67. https://doi.org/10.1016/j.pneurobio.2008.09.015.
Molofsky AV, Krencik R, Ullian EM, Tsai HH, Deneen B, Richardson WD, et al. Astrocytes and disease: a neurodevelopmental perspective. Genes Dev. 2012;26(9):891–907. https://doi.org/10.1101/gad.188326.112.
Tsai HH, Li H, Fuentealba LC, Molofsky AV, Taveira-Marques R, Zhuang H, et al. Regional astrocyte allocation regulates CNS synaptogenesis and repair. Science. 2012;337(6092):358–62. https://doi.org/10.1126/science.1222381.
Lundgaard I, Osorio MJ, Kress BT, Sanggaard S, Nedergaard M. White matter astrocytes in health and disease. Neuroscience. 2014;276:161–73. https://doi.org/10.1016/j.neuroscience.2013.10.050.
Sun D, Jakobs TC. Structural remodeling of astrocytes in the injured CNS. Neuroscientist. 2012;18(6):567–88. https://doi.org/10.1177/1073858411423441.
Bo L. The histopathology of grey matter demyelination in multiple sclerosis. Acta Neurol Scand Suppl. 2009;120(189):51–7. https://doi.org/10.1111/j.1600-0404.2009.01216.x.
Seifert G, Schilling K, Steinhauser C. Astrocyte dysfunction in neurological disorders: a molecular perspective. Nat Rev Neurosci. 2006;7(3):194–206. https://doi.org/10.1038/nrn1870.
Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 2006;7(1):41–53. https://doi.org/10.1038/nrn1824.
Iadecola C, Nedergaard M. Glial regulation of the cerebral microvasculature. Nat Neurosci. 2007;10(11):1369–76. https://doi.org/10.1038/nn2003.
Chesler M, Kaila K. Modulation of pH by neuronal activity. Trends Neurosci. 1992;15(10):396–402.
Dietschy JM, Turley SD. Thematic review series: brain lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J Lipid Res. 2004;45(8):1375–97. https://doi.org/10.1194/jlr.R400004-JLR200.
Magistretti PJ. Neuron-glia metabolic coupling and plasticity. J Exp Biol. 2006;209.(Pt 12:2304–11. https://doi.org/10.1242/jeb.02208.
Akwa Y, Sananes N, Gouezou M, Robel P, Baulieu EE, Le Goascogne C. Astrocytes and neurosteroids: metabolism of pregnenolone and dehydroepiandrosterone. Regulation by cell density. J Cell Biol. 1993;121(1):135–43.
Allen NJ, Eroglu C. Cell biology of astrocyte-synapse interactions. Neuron. 2017;96(3):697–708. https://doi.org/10.1016/j.neuron.2017.09.056.
Gimenez MA, Sim JE, Russell JH. TNFR1-dependent VCAM-1 expression by astrocytes exposes the CNS to destructive inflammation. J Neuroimmunol. 2004;151(1–2):116–25. https://doi.org/10.1016/j.jneuroim.2004.02.012.
Sobel RA, Mitchell ME, Fondren G. Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system. Am J Pathol. 1990;136(6):1309–16.
Dong Y, Benveniste EN. Immune function of astrocytes. Glia. 2001;36(2):180–90.
Miljkovic D, Momcilovic M, Stojanovic I, Stosic-Grujicic S, Ramic Z, Mostarica-Stojkovic M. Astrocytes stimulate interleukin-17 and interferon-gamma production in vitro. J Neurosci Res. 2007;85(16):3598–606. https://doi.org/10.1002/jnr.21453.
Zhou Y, Sonobe Y, Akahori T, Jin S, Kawanokuchi J, Noda M, et al. IL-9 promotes Th17 cell migration into the central nervous system via CC chemokine ligand-20 produced by astrocytes. J Immunol. 2011;186(7):4415–21. https://doi.org/10.4049/jimmunol.1003307.
Saikali P, Antel JP, Pittet CL, Newcombe J, Arbour N. Contribution of astrocyte-derived IL-15 to CD8 T cell effector functions in multiple sclerosis. J Immunol. 2010;185(10):5693–703. https://doi.org/10.4049/jimmunol.1002188.
Zhu C, Anderson AC, Kuchroo VK. TIM-3 and its regulatory role in immune responses. Curr Top Microbiol Immunol. 2011;350:1–15. https://doi.org/10.1007/82_2010_84.
Krumbholz M, Theil D, Derfuss T, Rosenwald A, Schrader F, Monoranu CM, et al. BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. J Exp Med. 2005;201(2):195–200. https://doi.org/10.1084/jem.20041674.
DeWitt DA, Perry G, Cohen M, Doller C, Silver J. Astrocytes regulate microglial phagocytosis of senile plaque cores of Alzheimer’s disease. Exp Neurol. 1998;149(2):329–40. https://doi.org/10.1006/exnr.1997.6738.
Chastain EM, Duncan DS, Rodgers JM, Miller SD. The role of antigen presenting cells in multiple sclerosis. Biochim Biophys Acta. 2011;1812(2):265–74. https://doi.org/10.1016/j.bbadis.2010.07.008.
Satoh J, Lee YB, Kim SU. T-cell costimulatory molecules B7-1 (CD80) and B7-2 (CD86) are expressed in human microglia but not in astrocytes in culture. Brain Res. 1995;704(1):92–6.
Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017;541(7638):481–7. https://doi.org/10.1038/nature21029.
Jha MK, Jo M, Kim JH, Suk K. Microglia-astrocyte crosstalk: an intimate molecular conversation. Neuroscientist. 2019;25(3):227–40. https://doi.org/10.1177/1073858418783959.
Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106–12. https://doi.org/10.1016/S0140-6736(04)17551-X.
Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol. 2007;6(9):805–15. https://doi.org/10.1016/S1474-4422(07)70216-8.
Agre P, Sasaki S, Chrispeels MJ. Aquaporins: a family of water channel proteins. Am J Phys. 1993;265(3. Pt 2):F461. https://doi.org/10.1152/ajprenal.1993.265.3.F461.
Zelenina M. Regulation of brain aquaporins. Neurochem Int. 2010;57(4):468–88. https://doi.org/10.1016/j.neuint.2010.03.022.
Rossi A, Pisani F, Nicchia GP, Svelto M, Frigeri A. Evidences for a leaky scanning mechanism for the synthesis of the shorter M23 protein isoform of aquaporin-4: implication in orthogonal array formation and neuromyelitis optica antibody interaction. J Biol Chem. 2010;285(7):4562–9. https://doi.org/10.1074/jbc.M109.069245.
Amiry-Moghaddam M, Williamson A, Palomba M, Eid T, de Lanerolle NC, Nagelhus EA, et al. Delayed K+ clearance associated with aquaporin-4 mislocalization: phenotypic defects in brains of alpha-syntrophin-null mice. Proc Natl Acad Sci U S A. 2003;100(23):13615–20. https://doi.org/10.1073/pnas.2336064100.
Arcienega II, Brunet JF, Bloch J, Badaut J. Cell locations for AQP1, AQP4 and 9 in the non-human primate brain. Neuroscience. 2010;167(4):1103–14. https://doi.org/10.1016/j.neuroscience.2010.02.059.
Popescu BF, Lennon VA, Parisi JE, Howe CL, Weigand SD, Cabrera-Gomez JA, et al. Neuromyelitis optica unique area postrema lesions: nausea, vomiting, and pathogenic implications. Neurology. 2011;76(14):1229–37. https://doi.org/10.1212/WNL.0b013e318214332c.
Lucchinetti CF, Guo Y, Popescu BF, Fujihara K, Itoyama Y, Misu T. The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica. Brain Pathol. 2014;24(1):83–97. https://doi.org/10.1111/bpa.12099.
Blanchard C, Rothenberg ME. Biology of the eosinophil. Adv Immunol. 2009;101:81–121. https://doi.org/10.1016/S0065-2776(08)01003-1.
Hinson SR, Romero MF, Popescu BF, Lucchinetti CF, Fryer JP, Wolburg H, et al. Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes. Proc Natl Acad Sci U S A. 2012;109(4):1245–50. https://doi.org/10.1073/pnas.1109980108.
Illarionova NB, Gunnarson E, Li Y, Brismar H, Bondar A, Zelenin S, et al. Functional and molecular interactions between aquaporins and Na,K-ATPase. Neuroscience. 2010;168(4):915–25. https://doi.org/10.1016/j.neuroscience.2009.11.062.
Hinson SR, Roemer SF, Lucchinetti CF, Fryer JP, Kryzer TJ, Chamberlain JL, et al. Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2. J Exp Med. 2008;205(11):2473–81. https://doi.org/10.1084/jem.20081241.
Iorio R, Lennon VA. Neural antigen-specific autoimmune disorders. Immunol Rev. 2012;248(1):104–21. https://doi.org/10.1111/j.1600-065X.2012.01144.x.
Fang B, McKeon A, Hinson SR, Kryzer TJ, Pittock SJ, Aksamit AJ, et al. Autoimmune glial fibrillary acidic protein astrocytopathy: a novel meningoencephalomyelitis. JAMA Neurol. 2016;73(11):1297–307. https://doi.org/10.1001/jamaneurol.2016.2549.
Flanagan EP, Hinson SR, Lennon VA, Fang B, Aksamit AJ, Morris PP, et al. Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: analysis of 102 patients. Ann Neurol. 2017;81(2):298–309. https://doi.org/10.1002/ana.24881.
Middeldorp J, Hol EM. GFAP in health and disease. Prog Neurobiol. 2011;93(3):421–43. https://doi.org/10.1016/j.pneurobio.2011.01.005.
Yang X, Liang J, Huang Q, Xu H, Gao C, Long Y, et al. Treatment of autoimmune glial fibrillary acidic protein astrocytopathy: follow-up in 7 cases. Neuroimmunomodulation. 2017;24(2):113–9. https://doi.org/10.1159/000479948.
Iorio R, Damato V, Evoli A, Gessi M, Gaudino S, Di Lazzaro V, et al. Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients. J Neurol Neurosurg Psychiatry. 2018;89(2):138–46. https://doi.org/10.1136/jnnp-2017-316583.
Dubey D, Hinson SR, Jolliffe EA, Zekeridou A, Flanagan EP, Pittock SJ, et al. Autoimmune GFAP astrocytopathy: prospective evaluation of 90 patients in 1 year. J Neuroimmunol. 2018;321:157–63. https://doi.org/10.1016/j.jneuroim.2018.04.016.
Li J, Xu Y, Ren H, Zhu Y, Peng B, Cui L. Autoimmune GFAP astrocytopathy after viral encephalitis: a case report. Mult Scler Relat Disord. 2018;21:84–7. https://doi.org/10.1016/j.msard.2018.02.020.
Gresa-Arribas N, Titulaer MJ, Torrents A, Aguilar E, McCracken L, Leypoldt F, et al. Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol. 2014;13(2):167–77. https://doi.org/10.1016/S1474-4422(13)70282-5.
Majed M, Fryer JP, McKeon A, Lennon VA, Pittock SJ. Clinical utility of testing AQP4-IgG in CSF: guidance for physicians. Neurol Neuroimmunol Neuroinflamm. 2016;3(3):e231. https://doi.org/10.1212/NXI.0000000000000231.
Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7(12):1091–8. https://doi.org/10.1016/S1474-4422(08)70224-2.
Zekeridou A, Lennon VA. Aquaporin-4 autoimmunity. Neurol Neuroimmunol Neuroinflamm. 2015;2(4):e110. https://doi.org/10.1212/NXI.0000000000000110.
Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003;349(16):1543–54. https://doi.org/10.1056/NEJMra023009.
Sasaki K, Bean A, Shah S, Schutten E, Huseby PG, Peters B, et al. Relapsing-remitting central nervous system autoimmunity mediated by GFAP-specific CD8 T cells. J Immunol. 2014;192(7):3029–42. https://doi.org/10.4049/jimmunol.1302911.
Long Y, Liang J, Xu H, Huang Q, Yang J, Gao C, et al. Autoimmune glial fibrillary acidic protein astrocytopathy in Chinese patients: a retrospective study. Eur J Neurol. 2018;25(3):477–83. https://doi.org/10.1111/ene.13531.
Yang X, Xu H, Ding M, Huang Q, Chen B, Yang H, et al. Overlapping autoimmune syndromes in patients with glial fibrillary acidic protein antibodies. Front Neurol. 2018;9:251. https://doi.org/10.3389/fneur.2018.00251.
McKeon A, Lennon VA, LaChance DH, Klein CJ, Pittock SJ. Striational antibodies in a paraneoplastic context. Muscle Nerve. 2013;47(4):585–7. https://doi.org/10.1002/mus.23774.
Klein RS, Hunter CA. Protective and pathological immunity during central nervous system infections. Immunity. 2017;46(6):891–909. https://doi.org/10.1016/j.immuni.2017.06.012.
Stenzel W, Soltek S, Schluter D, Deckert M. The intermediate filament GFAP is important for the control of experimental murine Staphylococcus aureus-induced brain abscess and Toxoplasma encephalitis. J Neuropathol Exp Neurol. 2004;63(6):631–40.
Esen N, Shuffield D, Syed MM, Kielian T. Modulation of connexin expression and gap junction communication in astrocytes by the gram-positive bacterium S. aureus. Glia. 2007;55(1):104–17. https://doi.org/10.1002/glia.20438.
Wilson EH, Hunter CA. The role of astrocytes in the immunopathogenesis of toxoplasmic encephalitis. Int J Parasitol. 2004;34(5):543–8. https://doi.org/10.1016/j.ijpara.2003.12.010.
Medana IM, Day NP, Hien TT, Mai NT, Bethell D, Phu NH, et al. Axonal injury in cerebral malaria. Am J Pathol. 2002;160(2):655–66. https://doi.org/10.1016/S0002-9440(10)64885-7.
Crill EK, Furr-Rogers SR, Marriott I. RIG-I is required for VSV-induced cytokine production by murine glia and acts in combination with DAI to initiate responses to HSV-1. Glia. 2015;63(12):2168–80. https://doi.org/10.1002/glia.22883.
Daniels BP, Holman DW, Cruz-Orengo L, Jujjavarapu H, Durrant DM, Klein RS. Viral pathogen-associated molecular patterns regulate blood-brain barrier integrity via competing innate cytokine signals. MBio. 2014;5(5):e01476–14. https://doi.org/10.1128/mBio.01476-14.
Cisneros IE, Ghorpade A. HIV-1, methamphetamine and astrocyte glutamate regulation: combined excitotoxic implications for neuro-AIDS. Curr HIV Res. 2012;10(5):392–406.
Hu X, Chakravarty SD, Ivashkiv LB. Regulation of interferon and toll-like receptor signaling during macrophage activation by opposing feedforward and feedback inhibition mechanisms. Immunol Rev. 2008;226:41–56. https://doi.org/10.1111/j.1600-065X.2008.00707.x.
Lin MT, Hinton DR, Marten NW, Bergmann CC, Stohlman SA. Antibody prevents virus reactivation within the central nervous system. J Immunol. 1999;162(12):7358–68.
Hamo L, Stohlman SA, Otto-Duessel M, Bergmann CC. Distinct regulation of MHC molecule expression on astrocytes and microglia during viral encephalomyelitis. Glia. 2007;55(11):1169–77. https://doi.org/10.1002/glia.20538.
Rasmussen T, Olszewski J, Lloydsmith D. Focal seizures due to chronic localized encephalitis. Neurology. 1958;8(6):435–45.
Farrell MA, Droogan O, Secor DL, Poukens V, Quinn B, Vinters HV. Chronic encephalitis associated with epilepsy: immunohistochemical and ultrastructural studies. Acta Neuropathol. 1995;89(4):313–21.
Bien CG, Granata T, Antozzi C, Cross JH, Dulac O, Kurthen M, et al. Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain. 2005;128(Pt 3):454–71. https://doi.org/10.1093/brain/awh415.
Bauer J, Elger CE, Hans VH, Schramm J, Urbach H, Lassmann H, et al. Astrocytes are a specific immunological target in Rasmussen’s encephalitis. Ann Neurol. 2007;62(1):67–80. https://doi.org/10.1002/ana.21148.
Rogers SW, Andrews PI, Gahring LC, Whisenand T, Cauley K, Crain B, et al. Autoantibodies to glutamate receptor GluR3 in Rasmussen’s encephalitis. Science. 1994;265(5172):648–51.
Andrews PI, Dichter MA, Berkovic SF, Newton MR, McNamara JO. Plasmapheresis in Rasmussen’s encephalitis. Neurology. 1996;46(1):242–6.
Twyman RE, Gahring LC, Spiess J, Rogers SW. Glutamate receptor antibodies activate a subset of receptors and reveal an agonist binding site. Neuron. 1995;14(4):755–62.
Whitney KD, McNamara JO. GluR3 autoantibodies destroy neural cells in a complement-dependent manner modulated by complement regulatory proteins. J Neurosci. 2000;20(19):7307–16.
Levite M, Hermelin A. Autoimmunity to the glutamate receptor in mice – a model for Rasmussen’s encephalitis? J Autoimmun. 1999;13(1):73–82. https://doi.org/10.1006/jaut.1999.0297.
Schwab N, Bien CG, Waschbisch A, Becker A, Vince GH, Dornmair K, et al. CD8+ T-cell clones dominate brain infiltrates in Rasmussen encephalitis and persist in the periphery. Brain. 2009;132.(Pt 5:1236–46. https://doi.org/10.1093/brain/awp003.
Mantegazza R, Bernasconi P, Baggi F, Spreafico R, Ragona F, Antozzi C, et al. Antibodies against GluR3 peptides are not specific for Rasmussen’s encephalitis but are also present in epilepsy patients with severe, early onset disease and intractable seizures. J Neuroimmunol. 2002;131(1–2):179–85.
Luan G, Gao Q, Zhai F, Chen Y, Li T. Upregulation of HMGB1, toll-like receptor and RAGE in human Rasmussen’s encephalitis. Epilepsy Res. 2016;123:36–49. https://doi.org/10.1016/j.eplepsyres.2016.03.005.
Bianchi ME, Manfredi AA. Immunology. Dangers in and out. Science. 2009;323(5922):1683–4. https://doi.org/10.1126/science.1172794.
Park JS, Arcaroli J, Yum HK, Yang H, Wang H, Yang KY, et al. Activation of gene expression in human neutrophils by high mobility group box 1 protein. Am J Physiol Cell Physiol. 2003;284(4):C870–9. https://doi.org/10.1152/ajpcell.00322.2002.
Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002;418(6894):191–5. https://doi.org/10.1038/nature00858.
Maroso M, Balosso S, Ravizza T, Liu J, Aronica E, Iyer AM, et al. Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat Med. 2010;16(4):413–9. https://doi.org/10.1038/nm.2127.
Walker L, Sills GJ. Inflammation and epilepsy: the foundations for a new therapeutic approach in epilepsy? Epilepsy Curr. 2012;12(1):8–12. https://doi.org/10.5698/1535-7511-12.1.8.
Brosnan CF, Raine CS. The astrocyte in multiple sclerosis revisited. Glia. 2013;61(4):453–65. https://doi.org/10.1002/glia.22443.
Pham H, Ramp AA, Klonis N, Ng SW, Klopstein A, Ayers MM, et al. The astrocytic response in early experimental autoimmune encephalomyelitis occurs across both the grey and white matter compartments. J Neuroimmunol. 2009;208(1–2):30–9. https://doi.org/10.1016/j.jneuroim.2008.12.010.
Ponath G, Ramanan S, Mubarak M, Housley W, Lee S, Sahinkaya FR, et al. Myelin phagocytosis by astrocytes after myelin damage promotes lesion pathology. Brain. 2017;140(2):399–413. https://doi.org/10.1093/brain/aww298.
Michel L, Touil H, Pikor NB, Gommerman JL, Prat A, Bar-Or A. B cells in the multiple sclerosis central nervous system: trafficking and contribution to CNS-compartmentalized inflammation. Front Immunol. 2015;6:636. https://doi.org/10.3389/fimmu.2015.00636.
Bal-Price A, Brown GC. Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity. J Neurosci. 2001;21(17):6480–91.
Hamby ME, Hewett JA, Hewett SJ. TGF-beta1 potentiates astrocytic nitric oxide production by expanding the population of astrocytes that express NOS-2. Glia. 2006;54(6):566–77. https://doi.org/10.1002/glia.20411.
Kumar S, Singh BK, Prasad AK, Parmar VS, Biswal S, Ghosh B. Ethyl 3′,4′,5′-trimethoxythionocinnamate modulates NF-kappaB and Nrf2 transcription factors. Eur J Pharmacol. 2013;700(1–3):32–41. https://doi.org/10.1016/j.ejphar.2012.12.004.
Rossi S, Motta C, Studer V, Barbieri F, Buttari F, Bergami A, et al. Tumor necrosis factor is elevated in progressive multiple sclerosis and causes excitotoxic neurodegeneration. Mult Scler. 2014;20(3):304–12. https://doi.org/10.1177/1352458513498128.
Matute C, Sanchez-Gomez MV, Martinez-Millan L, Miledi R. Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes. Proc Natl Acad Sci U S A. 1997;94(16):8830–5.
Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, et al. Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron. 1996;16(3):675–86.
Ouardouz M, Coderre E, Basak A, Chen A, Zamponi GW, Hameed S, et al. Glutamate receptors on myelinated spinal cord axons: I. GluR6 kainate receptors. Ann Neurol. 2009;65(2):151–9. https://doi.org/10.1002/ana.21533.
Ouardouz M, Coderre E, Zamponi GW, Hameed S, Yin X, Trapp BD, et al. Glutamate receptors on myelinated spinal cord axons: II. AMPA and GluR5 receptors. Ann Neurol. 2009;65(2):160–6. https://doi.org/10.1002/ana.21539.
Salter MG, Fern R. NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury. Nature. 2005;438(7071):1167–71. https://doi.org/10.1038/nature04301.
Pitt D, Werner P, Raine CS. Glutamate excitotoxicity in a model of multiple sclerosis. Nat Med. 2000;6(1):67–70. https://doi.org/10.1038/71555.
Franke H, Illes P. Pathological potential of astroglial purinergic receptors. Adv Neurobiol. 2014;11:213–56. https://doi.org/10.1007/978-3-319-08894-5_11.
Narcisse L, Scemes E, Zhao Y, Lee SC, Brosnan CF. The cytokine IL-1beta transiently enhances P2X7 receptor expression and function in human astrocytes. Glia. 2005;49(2):245–58. https://doi.org/10.1002/glia.20110.
Matute C, Torre I, Perez-Cerda F, Perez-Samartin A, Alberdi E, Etxebarria E, et al. P2X(7) receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis. J Neurosci. 2007;27(35):9525–33. https://doi.org/10.1523/JNEUROSCI.0579-07.2007.
Mayo L, Trauger SA, Blain M, Nadeau M, Patel B, Alvarez JI, et al. Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nat Med. 2014;20(10):1147–56. https://doi.org/10.1038/nm.3681.
Bundesen LQ, Scheel TA, Bregman BS, Kromer LF. Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. J Neurosci. 2003;23(21):7789–800.
Robel S, Berninger B, Gotz M. The stem cell potential of glia: lessons from reactive gliosis. Nat Rev Neurosci. 2011;12(2):88–104. https://doi.org/10.1038/nrn2978.
Balasingam V, Tejada-Berges T, Wright E, Bouckova R, Yong VW. Reactive astrogliosis in the neonatal mouse brain and its modulation by cytokines. J Neurosci. 1994;14(2):846–56.
Sherman LS, Struve JN, Rangwala R, Wallingford NM, Tuohy TM, Kuntz C. Hyaluronate-based extracellular matrix: keeping glia in their place. Glia. 2002;38(2):93–102.
Soilu-Hanninen M, Laaksonen M, Hanninen A, Eralinna JP, Panelius M. Downregulation of VLA-4 on T cells as a marker of long term treatment response to interferon beta-1a in MS. J Neuroimmunol. 2005;167(1–2):175–82. https://doi.org/10.1016/j.jneuroim.2005.06.022.
Back SA, Tuohy TM, Chen H, Wallingford N, Craig A, Struve J, et al. Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation. Nat Med. 2005;11(9):966–72. https://doi.org/10.1038/nm1279.
Johnson-Green PC, Dow KE, Riopelle RJ. Characterization of glycosaminoglycans produced by primary astrocytes in vitro. Glia. 1991;4(3):314–21. https://doi.org/10.1002/glia.440040309.
Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN, et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature. 2002;416(6881):636–40. https://doi.org/10.1038/416636a.
Yin HH, Knowlton BJ. The role of the basal ganglia in habit formation. Nat Rev Neurosci. 2006;7(6):464–76. https://doi.org/10.1038/nrn1919.
Zhu X, Bergles DE, Nishiyama A. NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development. 2008;135(1):145–57. https://doi.org/10.1242/dev.004895.
Fidler PS, Schuette K, Asher RA, Dobbertin A, Thornton SR, Calle-Patino Y, et al. Comparing astrocytic cell lines that are inhibitory or permissive for axon growth: the major axon-inhibitory proteoglycan is NG2. J Neurosci. 1999;19(20):8778–88.
Sobel RA. Ephrin A receptors and ligands in lesions and normal-appearing white matter in multiple sclerosis. Brain Pathol. 2005;15(1):35–45.
Wahl S, Barth H, Ciossek T, Aktories K, Mueller BK. Ephrin-A5 induces collapse of growth cones by activating Rho and Rho kinase. J Cell Biol. 2000;149(2):263–70.
Satoh J, Tabunoki H, Yamamura T, Arima K, Konno H. TROY and LINGO-1 expression in astrocytes and macrophages/microglia in multiple sclerosis lesions. Neuropathol Appl Neurobiol. 2007;33(1):99–107. https://doi.org/10.1111/j.1365-2990.2006.00787.x.
Fujita Y, Takashima R, Endo S, Takai T, Yamashita T. The p75 receptor mediates axon growth inhibition through an association with PIR-B. Cell Death Dis. 2011;2:e198. https://doi.org/10.1038/cddis.2011.85.
Williams A, Piaton G, Lubetzki C. Astrocytes – friends or foes in multiple sclerosis? Glia. 2007;55(13):1300–12. https://doi.org/10.1002/glia.20546.
Soung A, Klein RS. Viral encephalitis and neurologic diseases: focus on astrocytes. Trends Mol Med. 2018;24:950–62.
Acknowledgments
This work was supported by an unrestricted grant from FLENI.
The authors thank Dr. Ismael Calandri for preparation of some figures.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Correale, J., Gaitán, M.I. (2019). Autoimmune Astrocytopathy. In: Mitoma, H., Manto, M. (eds) Neuroimmune Diseases. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-030-19515-1_10
Download citation
DOI: https://doi.org/10.1007/978-3-030-19515-1_10
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-19514-4
Online ISBN: 978-3-030-19515-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)