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Cited by 177Complement system in diseasesNeuroinflammation and Neurodegeneration MechanismsBiomarkers in Disease Mechanisms

The complement cascade: Yin-Yang in neuroinflammation—neuro-protection and -degeneration

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Alexander, Jessy John, Anderson, Aileen Judith, Barnum, Scott Robert, Stevens, Beth, Tenner, Andrea Joan·2008·Journal of Neurochemistry
DOI 10.1111/j.1471-4159.2008.05668.xPMC PMC4038542
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Abstract

The complement cascade has long been recognized to play a key role in inflammatory and degenerative diseases. It is a ‘double edged’ sword as it is necessary to maintain health, yet can have adverse effects when unregulated, often exacerbating disease. The contrasting effects of complement, depending on whether in a setting of health or disease, is the price paid to achieve flexibility in scope and degree of a protective response for the host from infection and injury. Loss or even decreased efficiency of critical regulatory control mechanisms can result in aggravated inflammation and destruction of self‐tissue. The role of the complement cascade is poorly understood in the nervous system and neurological disorders. Novel studies have demonstrated that the expression of complement proteins in brain varies in different cell types and the effects of complement activation in various disease settings appear to differ. Understanding the functioning of this cascade is essential, as it has therapeutic implications. In this review, we will attempt to provide insight into how this complex cascade functions and to identify potential strategic targets for therapeutic intervention in chronic diseases as well as acute injury in the CNS.

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  • Abnormal microglia function and complement cascade activation have been associated with neurodegeneration of the CNS.

    “Consistent with this idea, abnormal microglia function and complement cascade activation have been associated with neurodegeneration of the CNS (Alexander et al., 2008; Beggs and Salter, 2010; Rosen and Stevens, 2010; Schafer and Stevens, 2010; Stephan et al. 2012).”

    From Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner (2012) · cites this paper as Alexander et al., 2008

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  1. Abbott NJ Mendonca LL Dolman DE 2003 The blood–brain barrier in systemic lupus erythematosus Lupus 12 908 915 14714910
  2. Afagh A Cummings BJ Cribbs DH Cotman CW Tenner AJ 1996 Localization and cell association of C1q in Alzheimer’s disease brain Exp Neurol 138 22 32 8593893
  3. Ahmed F Brown KM Stephan DA Morrison JC Johnson EC Tomarev SI 2004 Microarray analysis of changes in mRNA levels in the rat retina after experimental elevation of intraocular pressure Invest Ophthalmol Vis Sci 45 1247 1258 15037594
  4. Alexander JJ Quigg RJ 2007 Systemic lupus erythematosus and the brain: what mice are telling us Neurochem Int 50 5 11 16989923
  5. Alexander JJ Bao L Jacob A Kraus DM Holers VM Quigg RJ 2003 Administration of the soluble complement inhibitor, Crry-Ig, reduces inflammation and aquaporin 4 expression in lupus cerebritis Biochim Biophys Acta 1639 169 176 14636948
  6. Alexander JJ Zwingmann C Quigg R 2005a MRL/lpr mice have alterations in brain metabolism as shown with [1H-13C] NMR spectroscopy Neurochem Int 47 143 151 15893408
  7. Alexander JJ Jacob A Bao L Macdonald RL Quigg RJ 2005b Complement-dependent apoptosis and inflammatory gene changes in murine lupus cerebritis J Immunol 175 8312 8319 16339572
  8. Alexander JJ Jacob A Vezina P Sekine H Gilkeson GS Quigg RJ 2007 Absence of functional alternative complement pathway alleviates lupus cerebritis Eur J Immunol 37 1691 1701 17523212
  9. Allen NJ Barres BA 2005 Signaling between glia and neurons: focus on synaptic plasticity Curr Opin Neurobiol 15 542 548 16144764
  10. Ambrus JLJr Peters MG Fauci AS Brown EJ 1990 The Ba fragment of complement factor B inhibits human B lymphocyte proliferation J Immunol 144 1549 1553 2307833
  11. Anderson AJ 2002 Mechanisms and pathways of inflammatory responses in CNS trauma: spinal cord injury J Spinal Cord Med 25 70 79 12137220
  12. Anderson AJ Robert S Huang W Young W Cotman CW 2004 Activation of complement pathways as a components of the inflammatory response after contusion-induced spinal cord injury J Neurotrauma 21 1831 1836 15684772
  13. Anderson AJ Robert S Huang W Young W Cotman CW 2005 Upregulation of complement inhibitors in association with vulnerable cells following acute contusion-induced spinal cord injury J Neurotrauma 22 382 397 15785233
  14. Antel J Bar-Or A 2006 Roles of immunoglobulins and B cells in multiple sclerosis: from pathogenesis to treatment J Neuroimmunol 180 3 8 16934338
  15. Aringer M Feierl E Steiner G Stummvoll GH Hofler E Steiner CW Radda I Smole JS Graninger WB 2002 Increased bioactive TNF in human systemic lupus erythematosus: associations with cell death Lupus 11 102 108 11958572
  16. Ashe KH 2001 Learning and memory in transgenic mice modeling Alzheimer’s disease Learn Mem 8 301 308 11773429
  17. Atkinson C Song H Lu B Qiao F Burns TA Holers VM Tsokos GC Tomlinson S 2005 Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection J Clin Invest 115 2444 2453 16127466 PMC1190375
  18. Atkinson C Zhu H Qiao F Varela JC Yu J Song H Kindy MS Tomlinson S 2006 Complement-dependent P-selectin expression and injury following ischemic stroke J Immunol 177 7266 7274 17082645
  19. Atkinson C Qiao F Song H Gilkeson GS Tomlinson S 2008 Low-dose targeted complement inhibition protects against renal disease and other manifestations of autoimmune disease in MRL/lpr mice J Immunol 180 1231 1238 18178863
  20. Baca V Lavalle C Garcia R Catalan T Sauceda JM Sanchez G Martinez I Ramirez ML Marquez LM Rojas JC 1999 Favorable response to intravenous methylprednisolone and cyclophosphamide in children with severe neuropsychiatric lupus J Rheumatol 26 432 439 9972981
  21. Barnett MH Prineas JW 2004 Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion Ann Neurol 55 458 468 15048884
  22. Barnum SR Bondy SC Campbell A 2001 The complement system in demyelinating disease: new insights from transgenic and complement-deficient mice Inflammatory Events in Neurodegeneration 139 156 Prominent Press Scottsdale
  23. Barnum SR Szalai AJ 2006 Complement and demyelinating disease: no MAC needed? Brain Res Rev 52 58 68 16443278
  24. Belegu V Oudega M Gary DS McDonald JW 2007 Restoring function after spinal cord injury: promoting spontaneous regeneration with stem cells and activity-based therapies Neurosurg Clin N Am 18 143 168 17244561
  25. Belmont HM Hopkins P Edelson HS Kaplan HB Ludewig R Weissmann G Abramson S 1986 Complement activation during systemic lupus erythematosus. C3a and C5a anaphylatoxins circulate during exacerbations of disease Arthritis Rheum 29 1085 1089 3489467
  26. Belmont HM Abramson SB Lie JT 1996 Pathology and pathogenesis of vascular injury in systemic lupus erythematosus. Interactions of inflammatory cells and activated endothelium Arthritis Rheum 39 9 22 8546744
  27. Bensa JC Reboul A Colomb MG 1983 Biosynthesis in vitro of complement subcomponents C1q, C1s and C1 inhibitor by resting and stimulated human monocytes Biochem J 216 385 392 6318736 PMC1152515
  28. Bergamaschini L Rossi E Storini C Pizzimenti S Distaso M Perego C De Luigi A Vergani C De Simoni MG 2004 Peripheral treatment with enoxaparin, a low molecular weight heparin, reduces plaques and beta-amyloid accumulation in a mouse model of Alzheimer’s disease J Neurosci 24 4181 4186 15115813 PMC6729286
  29. Blalock EM Geddes JW Chen KC Porter NM Markesbery WR Landfield PW 2004 Incipient Alzheimer’s disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses Proc Natl Acad Sci USA 101 2173 2178 14769913 PMC357071
  30. Bohlson SS Fraser DA Tenner AJ 2007 Complement proteins C1q and MBL are pattern recognition molecules that signal immediate and long-term protective immune functions Mol Immunol 44 33 43 16908067
  31. Boos L Campbell IL Ames R Wetsel RA Barnum SR 2004 Deletion of the complement anaphylatoxin C3a receptor attenuates, whereas ectopic expression of C3a in the brain exacerbates, experimental autoimmune encephalomyelitis J Immunol 173 4708 4714 15383607
  32. Boos LA Szalai AJ Barnum SR 2005 Murine complement C4 is not required for experimental autoimmune encephalomyelitis Glia 49 158 160 15390104
  33. Botto M Dell’Agnola C Bygrave AE Thompson EM Cook HT Petry F Loos M Pandolfi PP Walport MJ 1998 Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies Nat Genet 19 56 59 9590289
  34. Bradt BM Kolb WP Cooper NR 1998 Complement-dependent proinflammatory properties of the Alzheimer’s disease beta-peptide J Exp Med 188 431 438 9687521 PMC2212467
  35. Brey RL Amato AA Kagan-Hallet K Rhine CB Stallworth CL 1997 Anti-intercellular adhesion molecule-1 (ICAM-1) antibody treatment prevents central and peripheral nervous system disease in autoimmune-prone mice Lupus 6 645 651 9364423
  36. Brey RL Holliday SL Saklad AR 2002 Neuropsychiatric syndromes in lupus: prevalence using standardized definitions Neurology 58 1214 1220 11971089
  37. Brink BP Veerhuis R Breij EC van der Valk P Dijkstra CD Bo L 2005 The pathology of multiple sclerosis is location-dependent: no significant complement activation is detected in purely cortical lesions J Neuropathol Exp Neurol 64 147 155 15751229
  38. Brooks WM Sabet A Sibbitt WLJr Barker PB van Zijl PC Duyn JH Moonen CT 1997 Neurochemistry of brain lesions determined by spectroscopic imaging in systemic lupus erythematosus J Rheumatol 24 2323 2329 9415636
  39. Brück W Friede RL 1990 Anti-macrophage CR3 antibody blocks myelin phagocytosis by macrophages in vitro Acta Neuropathol 80 415 418 2239153
  40. Bullard DC Hu X Schoeb TR Axtell RC Raman C Barnum SR 2005 Critical requirement of CD11b (Mac-1) on T cells and accessory cells for development of experimental autoimmune encephalomyelitis J Immunol 175 6327 6333 16272284
  41. Bullard DC Hu X Adams JE Schoeb TR Barnum SR 2007 p150,95 (CD11c/CD18) expression is required for the development of experimental autoimmune encephalomyelitis Am J Pathol 170 2001 2008 17525267 PMC1899456
  42. Buyon JP Tamerius J Ordorica S Young B Abramson SB 1992 Activation of the alternative complement pathway accompanies disease flares in systemic lupus erythematosus during pregnancy Arthritis Rheum 35 55 61 1731815
  43. Chaudhry N Filbin MT 2007 Myelin-associated inhibitory signaling and strategies to overcome inhibition J Cereb Blood Flow Metab 27 1096 1107 17033690
  44. Chen ZJ Ughrin Y Levine JM 2002 Inhibition of axon growth by oligodendrocyte precursor cells Mol Cell Neurosci 20 125 139 12056844
  45. Chinn RJ Wilkinson ID Hall-Craggs MA Paley MN Shortall E Carter S Kendall BE Isenberg DA Newman SP Harrison MJ 1997 Magnetic resonance imaging of the brain and cerebral proton spectroscopy in patients with systemic lupus erythematosus Arthritis Rheum 40 36 46 9008598
  46. Crowe MJ Bresnahan JC Shuman SL Masters JN Beattie MS 1997 Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys Nat Med 3 73 76 8986744
  47. Cudrici C Niculescu T Niculescu F Shin ML Rus H 2006a Oligodendrocyte cell death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from apoptosis by complement J Rehabil Res Dev 43 123 132 16847778
  48. Cudrici C Niculescu F Jensen T Zafranskaia E Fosbrink M Rus V Shin ML Rus H 2006b C5b-9 terminal complex protects oligodendrocytes from apoptotic cell death by inhibiting caspase-8 processing and up-regulating FLIP J Immunol 176 3173 3180 16493077
  49. Dailey AT Avellino AM Benthem L Silver J Kliot M 1998 Complement depletion reduces macrophage infiltration and activation during Wallerian degeneration and axonal regeneration J Neurosci 18 6713 6722 9712643 PMC6792968
  50. Dalmau I Finsen B Zimmer J Gonzalez B Castellano B 1998 Development of microglia in the postnatal rat hippocampus Hippocampus 8 458 474 9825958
  51. Danchenko N Satia JA Anthony MS 2006 Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden Lupus 15 308 318 16761508
  52. Davies SJ Fitch MT Memberg SP Hall AK Raisman G Silver J 1997 Regeneration of adult axons in white matter tracts of the central nervous system Nature 390 680 683 9414159
  53. Davoust N Nataf S Reiman R Holers MV Campbell IL Barnum SR 1999 Central nervous system-targeted expression of the complement inhibitor sCrry prevents experimental allergic encephalomyelitis J Immunol 163 6551 6556 10586048
  54. De Jager PL Hafler DA 2007 New therapeutic approaches for multiple sclerosis Annu Rev Med 58 417 432 17217332
  55. Donnelly DJ Popovich PG 2007 Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury Exp Neurol 209 378 388 17662717 PMC2692462
  56. Echeverria V Cuello AC 2002 Intracellular A-beta amyloid, a sign for worse things to come? Mol Neurobiol 26 299 316 12428762
  57. Eikelenboom P Stam FC 1984 An immunohistochemical study on cerebral vascular and senile plaque amyloid in Alzheimer’s dementia Virchows Arch B Cell Pathol Incl Mol Pathol 47 17 25 6151285
  58. Eng LF Ghirnikar RS 1994 GFAP and astrogliosis Brain Pathol 4 229 237 7952264
  59. Estes D Christian CL 1971 The natural history of systemic lupus erythematosus by prospective analysis Medicine (Baltimore) 50 85 95 4109481
  60. Faulkner JR Herrmann JE Woo MJ Tansey KE Doan NB Sofroniew MV 2004 Reactive astrocytes protect tissue and preserve function after spinal cord injury J Neurosci 24 2143 2155 14999065 PMC6730429
  61. Fawcett JW 2006 Overcoming inhibition in the damaged spinal cord J Neurotrauma 23 371 383 16629623
  62. Fawcett JW Asher RA 1999 The glial scar and central nervous system repair Brain Res Bull 49 377 391 10483914
  63. Fiske BK Brunjes PC 2000 Microglial activation in the developing rat olfactory bulb Neuroscience 96 807 815 10727798
  64. Fitch MT Doller C Combs CK Landreth GE Silver J 1999 Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma J Neurosci 19 8182 8198 10493720 PMC6783021
  65. Fleming JC Norenberg MD Ramsay DA Dekaban GA Marcillo AE Saenz AD Pasquale-Styles M Dietrich WD Weaver LC 2006 The cellular inflammatory response in human spinal cords after injury Brain 129 3249 3269 17071951
  66. Fox RJ Ransohoff RM 2004 New directions in MS therapeutics: vehicles of hope Trends Immunol 25 632 636 15530830
  67. Fraser DA Bohlson SS Jasinskiene N Rawal N Palmarini G Ruiz S Rochford R Tenner AJ 2006 C1q and MBL, components of the innate immune system, influence monocyte cytokine expression J Leukoc Biol 80 107 116 16617157
  68. Fujio Y Walsh K 1999 Akt mediates cytoprotection of endothelial cells by vascular endothelial growth factor in an anchorage-dependent manner J Biol Chem 274 16349 16354 10347193 PMC3624707
  69. Galvan M Anderson AJ 2008 Deficiency in complement C1q improves histological and functional locomotor outcome after SCI J Neurosci (in press) PMC2680920 19091977
  70. Gasque P Fontaine M Morgan BP 1995 Complement expression in human brain. Biosynthesis of terminal pathway components and regulators in human glial cells and cell lines J Immunol 154 4726 4733 7536777
  71. Gasque P Dean YD McGreal EP VanBeek J Morgan BP 2000 Complement components of the innate immune system in health and disease in the CNS Immunopharmacology 49 171 186 10904116
  72. Gonzenbach RR Schwab ME 2008 Disinhibition of neurite growth to repair the injured adult CNS: focusing on Nogo Cell Mol Life Sci 65 161 176 17975707 PMC11131900
  73. Griffin RS Costigan M Brenner GJ Ma CH Scholz J Moss A Allchorne AJ Stahl GL Woolf CJ 2007 Complement induction in spinal cord microglia results in anaphylatoxin C5a-mediated pain hypersensitivity J Neurosci 27 8699 8708 17687047 PMC6672952
  74. Handa R Sahota P Kumar M Jagannathan NR Bal CS Gulati M Tripathi BM Wali JP 2003 In vivo proton magnetic resonance spectroscopy (MRS) and single photon emission computerized tomography (SPECT) in systemic lupus erythematosus (SLE) Magn Reson Imaging 21 1033 1037 14684208
  75. Hemmer B Kieseier B Cepok S Hartung HP 2003 New immunopathologic insights into multiple sclerosis Curr Neurol Neurosci Rep 3 246 255 12691630 PMC7088761
  76. Hemmer B Stuve O Kieseier B Schellekens H Hartung HP 2005 Immune response to immunotherapy: the role of neutralising antibodies to interferon beta in the treatment of multiple sclerosis Lancet Neurol 4 403 412 15963443
  77. Hjelmstrom P Juedes AE Fjell J Ruddle NH 1998 B-cell-deficient mice develop experimental allergic encephalomyelitis with demyelination after myelin oligodendrocyte glycoprotein sensitization J Immunol 161 4480 4483 9794370
  78. Hooks BM Chen C 2006 Distinct roles for spontaneous and visual activity in remodeling of the retinogeniculate synapse Neuron 52 281 291 17046691
  79. Hopkins P Belmont HM Buyon J Philips M Weissmann G Abramson SB 1988 Increased levels of plasma anaphylatoxins in systemic lupus erythematosus predict flares of the disease and may elicit vascular injury in lupus cerebritis Arthritis Rheum 31 632 641 3259882
  80. van Horssen J Bo 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 16106221
  81. Howell GR Libby RT Marchant JK Wilson LA Cosma IM Smith RS Anderson MG John SW 2007 Absence of glaucoma in DBA/2J mice homozygous for wild-type versions of Gpnmb and Tyrp1 BMC Genet 8 45 17608931 PMC1937007
  82. Hsiao K Chapman P Nilsen S Eckman C Harigaya Y Younkin S Yang F Cole G 1996 Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice Science 274 99 102 8810256
  83. Hua JY Smith SJ 2004 Neural activity and the dynamics of central nervous system development Nat Neurosci 7 327 332 15048120
  84. Huber-Lang M Sarma V Zetoune FS 2006 Generation of C5a in the absence of C3: a new complement activation pathway Nat Med 12 682 687 16715088
  85. Husebye ES Sthoeger ZM Dayan M Zinger H Elbirt D Levite M Mozes E 2005 Autoantibodies to a NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus Ann Rheum Dis 64 1210 1213 15708887 PMC1755620
  86. Jakobs TC Libby RT Ben Y John SW Masland RH 2005 Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice J Cell Biol 171 313 325 16247030 PMC2171185
  87. John SW Anderson MG Smith RS 1999 Mouse genetics: a tool to help unlock the mechanisms of glaucoma J Glaucoma 8 400 412 10604301
  88. Jones TB McDaniel EE Popovich PG 2005 Inflammatory-mediated injury and repair in the traumatically injured spinal cord Curr Pharm Des 11 1223 1236 15853679
  89. Jongen PJ Doesburg WH Ibrahim-Stappers JL Lemmens WA Hommes OR Lamers KJ 2000 Cerebrospinal fluid C3 and C4 indexes in immunological disorders of the central nervous system Acta Neurol Scand 101 116 121 10685859
  90. Katschke KJJr Helmy KY Steffek M 2007 A novel inhibitor of the alternative pathway of complement reverses inflammation and bone destruction in experimental arthritis J Exp Med 204 1319 1325 17548523 PMC2118595
  91. Katz LC Shatz CJ 1996 Synaptic activity and the construction of cortical circuits Science 274 1133 1138 8895456
  92. Kigerl KA McGaughy VM Popovich PG 2006 Comparative analysis of lesion development and intraspinal inflammation in four strains of mice following spinal contusion injury J Comp Neurol 494 578 594 16374800 PMC2655318
  93. Klawiter EC Cross AH 2007 B cells: no longer the dominant arm of multiple sclerosis Curr Neurol Neurosci Rep 7 231 238 17488589
  94. Lambert WC Cohen PJ Klein KM Lambert MW 1984 Cellular and molecular mechanisms in wound healing: selected concepts Clin Dermatol 2 17 23 6545766
  95. Libby RT Anderson MG Pang IH 2005 Inherited glaucoma in DBA/2J mice: pertinent disease features for studying the neurodegeneration Vis Neurosci 22 637 648 16332275
  96. Liu L Lioudyno M Tao R Eriksson P Svensson M Aldskogius H 1999 Hereditary absence of complement C5 in adult mice influences Wallerian degeneration, but not retrograde responses, following injury to peripheral nerve J Peripher Nerv Syst 4 123 133 10442688
  97. Loeffler DA Camp DM Schonberger MB Singer DJ LeWitt PA 2004 Early complement activation increases in the brain in some aged normal subjects Neurobiol Aging 25 1001 1007 15212824
  98. Loeffler DA Camp DM Bennett DA 2008 Plaque complement activation and cognitive loss in Alzheimer’s disease J Neuroinflammation 5 9 18334032 PMC2292690
  99. Lucchinetti C Bruck 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 10852536
  100. Maier M Peng Y Jiang L Seabrook TJ Carroll MC Lemere CA 2008 Complement C3 deficiency leads to accelerated amyloid beta plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice J Neurosci 28 6333 6341 18562603 PMC3329761
  101. Maslinska D Laure-Kamionowska M Kaliszek A 1998 Morphological forms and localization of microglial cells in the developing human cerebellum Folia Neuropathol 36 145 151 9833391
  102. Mastellos D Andronis C Persidis A Lambris JD 2005 Novel biological networks modulated by complement Clin Immunol 115 225 235 15893689
  103. Matsuoka Y Picciano M Malester B 2001 Inflammatory responses to amyloidosis in a transgenic mouse model of Alzheimer’s disease Am J Pathol 158 1345 1354 11290552 PMC1891893
  104. McFarland HF Martin R 2007 Multiple sclerosis: a complicated picture of autoimmunity Nat Immunol 8 913 919 17712344
  105. Mead RJ Singhrao SK Neal JW Lassmann H Morgan BP 2002 The membrane attack complex of complement causes severe demyelination associated with acute axonal injury J Immunol 168 458 465 11751993
  106. Milligan CE Cunningham TJ Levitt P 1991 Differential immunochemical markers reveal the normal distribution of brain macrophages and microglia in the developing rat brain J Comp Neurol 314 125 135 1797868
  107. Miyahara T Kikuchi T Akimoto M Kurokawa T Shibuki H Yoshimura N 2003 Gene microarray analysis of experimental glaucomatous retina from cynomologous monkey Invest Ophthalmol Vis Sci 44 4347 4356 14507879
  108. Morariu MA Dalmasso AP 1978 Experimental allergic encephalomyelitis in cobra venom factor-treated and C4-deficient guinea pigs Ann Neurol 4 427 430 83812
  109. Morgan BP Campbell AK Compston DA 1984 Terminal component of complement (C9) in cerebrospinal fluid of patients with multiple sclerosis Lancet 2 251 254 6146808
  110. Mukherjee P Pasinetti GM 2001 Complement anaphylatoxin C5a neuroprotects through mitogen-activated protein kinase-dependent inhibition of caspase 3 J Neurochem 77 43 49 11279260
  111. Mukherjee P Thomas S Pasinetti GM 2008 Complement anaphylatoxin C5a neuroprotects through regulation of glutamate receptor subunit 2 in vitro and in vivo J Neuroinflammation 5 5 18230183 PMC2246107
  112. Nataf S Carroll SL Wetsel RA Szalai AJ Barnum SR 2000 Attenuation of experimental autoimmune demyelination in complement-deficient mice J Immunol 165 5867 5873 11067947
  113. Nauta AJ Daha MR Tijsma O van de Water B Tedesco F Roos A 2002 The membrane attack complex of complement induces caspase activation and apoptosis Eur J Immunol 32 783 792 11870622
  114. Nauta AJ Roos A Daha MR 2004 A regulatory role for complement in innate immunity and autoimmunity Int Arch Allergy Immunol 134 310 323 15218334
  115. Nguyen MD Julien JP Rivest S 2002 Innate immunity: the missing link in neuroprotection and neurodegeneration? Nat Rev Neurosci 3 216 227 11994753
  116. Nguyen HX O’Barr TJ Anderson AJ 2007 Polymorphonuclear leukocytes promote neurotoxicity through release of matrix metalloproteinases, reactive oxygen species, and TNF-alpha J Neurochem 102 900 912 17561941
  117. Nguyen HX Galvan MD Anderson AJ 2008 Neutrophils express the early components of the complement system J Neuroinflammation 5 26 38 18578885 PMC2443364
  118. Ong GL Mattes MJ 1989 Mouse strains with typical mammalian levels of complement activity J Immunol Methods 125 147 158 2607149
  119. Ong GL Baker AE Mattes MJ 1992 Analysis of high complement levels in Mus hortulanus and BUB mice J Immunol Methods 154 37 45 1401942
  120. Osaka H Mukherjee P Aisen PS Pasinetti GM 1999 Complement-derived anaphylatoxin C5a protects against glutamate-mediated neurotoxicity J Cell Biochem 73 303 311 10321830
  121. Osmers I Szalai AJ Tenner AJ Barnum SR 2006 Complement in BuB/BnJ mice revisited: serum C3 levels and complement opsonic activity are not elevated Mol Immunol 43 1722 1725 16310250
  122. Owens T 2003 The enigma of multiple sclerosis: inflammation and neurodegeneration cause heterogeneous dysfunction and damage Curr Opin Neurol 16 259 265 12858060
  123. Peters MG Ambrus JL Jr Fauci AS Brown EJ 1988 The Bb fragment of complement factor B acts as a B cell growth factor J Exp Med 168 1225 1235 3262708 PMC2189078
  124. Pisalyaput K Tenner AJ 2008 Complement component C1q inhibits beta-amyloid- and serum amyloid P-induced neurotoxicity via caspase- and calpain-independent mechanisms J Neurochem 104 696 707 17986223
  125. Popovich PG Jones TB 2003 Manipulating neuroinflammatory reactions in the injured spinal cord: back to basics Trends Pharmacol Sci 24 13 17 12498725
  126. Qiao F Atkinson C Song H Pannu R Singh I Tomlinson S 2006 Complement plays an important role in spinal cord injury and represents a therapeutic target for improving recovery following trauma Am J Pathol 169 1039 1047 16936276 PMC1698827
  127. Rahpeymai Y Hietala MA Wilhelmsson U 2006 Complement: a novel factor in basal and ischemia-induced neurogenesis EMBO J 25 1364 1374 16498410 PMC1422160
  128. Ramaglia V King RH Nourallah M 2007 The membrane attack complex of the complement system is essential for rapid Wallerian degeneration J Neurosci 27 7663 7672 17634361 PMC6672891
  129. Ransohoff RM 2006 EAE: pitfalls outweigh virtues of screening potential treatments for multiple sclerosis Trends Immunol 27 167 168 16513422
  130. Rebhun J Botvin J 1980 Complement elevation in spinal cord injury Ann Allergy 44 287 288 6966477
  131. Reiman R Gerard C Campbell IL Barnum SR 2002 Disruption of the C5a receptor gene fails to protect against experimental allergic encephalomyelitis Eur J Immunol 32 1157 1163 11932923
  132. Reiman R Torres AC Martin BK Ting JP Campbell IL Barnum SR 2005 Expression of C5a in the brain does not exacerbate experimental autoimmune encephalomyelitis Neurosci Lett 390 134 138 16154690
  133. Reynolds DN Smith SA Zhang YP Mengsheng Q Lahiri DK Morassutti DJ Shields CB Kotwal GJ 2004 Vaccinia virus complement control protein reduces inflammation and improves spinal cord integrity following spinal cord injury Ann NY Acad Sci 1035 165 178 15681807
  134. Ricklin D Lambris JD 2007 Complement-targeted therapeutics Nat Biotechnol 25 1265 1275 17989689 PMC2966895
  135. Rodriguez M Wynn DR Kimlinger TK Katzmann JA 1990 Terminal component of complement (C9) in the cerebrospinal fluid of patients with multiple sclerosis and neurologic controls Neurology 40 855 857 2330118
  136. Rogers J Schultz J Brachova L Lue LF Webster S Bradt B Cooper NR Moss DE 1992 Complement activation and beta-amyloid-mediated neurotoxicity in Alzheimer’s disease Res Immunol 143 624 630 1455054
  137. Rozovsky I Morgan TE Willoughby DA Dugichi-Djordjevich MM Pasinetti GM Johnson SA Finch CE 1994 Selective expression of clusterin (SGP-2) and complement C1qB and C4 during responses to neurotoxins in vivo and in vitro Neuroscience 62 741 758 7870303
  138. Rus H Cudrici C Niculescu F 2005 C5b-9 complement complex in autoimmune demyelination and multiple sclerosis: dual role in neuroinflammation and neuroprotection Ann Med 37 97 104 16026117
  139. Rus H Cudrici C Niculescu F 2006a C5b-9 complement complex in autoimmune demyelination: dual role in neuroinflammation and neuroprotection Adv Exp Med Biol 586 139 151 16893070
  140. Rus H Cudrici C David S Niculescu F 2006b The complement system in central nervous system diseases Autoimmunity 39 395 402 16923539
  141. Sakic B Szechtman H Keffer M Talangbayan H Stead R Denburg JA 1992 A behavioral profile of autoimmune lupusprone MRL mice Brain Behav Immun 6 265 285 1392101
  142. Sari RA Taysi S Erdem F Yilmaz O Keles S Kiziltunc A Odabas AR Cetinkaya R 2002 Correlation of serum levels of soluble intercellular adhesion molecule-1 with disease activity in systemic lupus erythematosus Rheumatol Int 21 149 152 11843170
  143. Segurado OG Gomez-Reino J Arnaiz-Villena A 1990 Factor B activation in systemic lupus erythematosus Arthritis Rheum 33 1598 1599 2222545
  144. Selkoe DJ 2002 Alzheimer’s disease is a synaptic failure Science 298 789 791 12399581
  145. Shen Y Meri S 2003 Yin and Yang: complement activation and regulation in Alzheimer’s disease Prog Neurobiol 70 463 472 14568360
  146. Shen Y Lue L Yang L 2001 Complement activation by neurofibrillary tangles in Alzheimer’s disease Neurosci Lett 305 165 168 11403931
  147. Shin ML Koski CL Martenson RE 1992 The complement system in demyelination Myelin: Biology and Chemistry 1 801 831 CRC Press Boca Raton, FL
  148. Silver J Miller JH 2004 Regeneration beyond the glial scar Nat Rev Neurosci 5 146 156 14735117
  149. Soane L Rus H Niculescu F Shin ML 1999 Inhibition of oligodendrocyte apoptosis by sublytic C5b-9 is associated with enhanced synthesis of bcl-2 and mediated by inhibition of caspase-3 activation J Immunol 163 6132 6138 10570303
  150. Sofroniew MV 2005 Reactive astrocytes in neural repair and protection Neuroscientist 11 400 407 16151042
  151. Spitzer D Wu X Ma X Xu L Ponder KP Atkinson JP 2006 Cutting edge: treatment of complement regulatory protein deficiency by retroviral in vivo gene therapy J Immunol 177 4953 4956 17015675
  152. Stahel PF Barnum SR 2006 The role of the complement system in CNS inflammatory diseases Expert Rev Clin Immunol 2 445 456 20476915
  153. Stasi K Nagel D Yang X Wang RF Ren L Podos SM Mittag T Danias J 2006 Complement component 1Q (C1Q) upregulation in retina of murine, primate, and human glaucomatous eyes Invest Ophthalmol Vis Sci 47 1024 1029 16505037
  154. Steele MR Inman DM Calkins DJ Horner PJ Vetter ML 2006 Microarray analysis of retinal gene expression in the DBA/2J model of glaucoma Invest Ophthalmol Vis Sci 47 977 985 16505032
  155. Stevens B Allen NJ Vazquez LE 2007 The classical complement cascade mediates CNS synapse elimination Cell 131 1164 1178 18083105
  156. Stojanovich L Stojanovich R Kostich V Dzjolich E 2003 Neuropsychiatric lupus favourable response to low dose i.v cyclophosphamide and prednisolone (pilot study) Lupus 12 3 7 12587819
  157. Stoltzner SE Grenfell TJ Mori C Wisniewski KE Wisniewski TM Selkoe DJ Lemere CA 2000 Temporal accrual of complement proteins in amyloid plaques in Down’s syndrome with Alzheimer’s disease Am J Pathol 156 489 499 10666378 PMC1850044
  158. Storch MK Piddlesden S Haltia M Iivanainen M Morgan P Lassmann H 1998 Multiple sclerosis: in situ evidence for antibody- and complement- mediated demyelination Ann Neurol 43 465 471 9546327
  159. Strey CW Markiewski M Mastellos D Tudoran R Spruce LA Greenbaum LE Lambris JD 2003 The proinflammatory mediators C3a and C5a are essential for liver regeneration J Exp Med 198 913 923 12975457 PMC2194207
  160. Tanihara H Hangai M Sawaguchi S Abe H Kageyama M Nakazawa F Shirasawa E Honda Y 1997 Up-regulation of glial fibrillary acidic protein in the retina of primate eyes with experimental glaucoma Arch Ophthalmol 115 752 756 9194727
  161. Tanzi RE Bertram L 2005 Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective Cell 120 545 555 15734686
  162. Tenner AJ Pisalyaput K Lane TE Carson MJ Bergmann C Wyss-Coray T 2008 The complement system in the CNS: thinking again Central Nervous System Disease and Inflammation 153 174 Springer New York
  163. Tenner AJ Webster S Bondy SC Campbell AC 2001 Complement-mediated injury and inflammation in the pathogenesis of Alzheimer’s disease Inflammatory Events in Neurodegeneration 119 138 Prominent Press Scottsdale
  164. Tornqvist E Liu L Aldskogius H Holst HV Svensson M 1996 Complement and clusterin in the injured nervous system Neurobiol Aging 17 695 705 8892342
  165. Trouw LA Blom AM Gasque P 2008 Role of complement and complement regulators in the removal of apoptotic cells Mol Immunol 45 1199 1207 17961651
  166. Twining CM Sloane EM Schoeniger DK Milligan ED Martin D Marsh H Maier SF Watkins LR 2005 Activation of the spinal cord complement cascade might contribute to mechanical allodynia induced by three animal models of spinal sensitization J Pain 6 174 183 15772911
  167. Ullian EM Christopherson KS Barres BA 2004 Role for glia in synaptogenesis Glia 47 209 216 15252809
  168. Uwai M Terui Y Mishima Y 2000 A new apoptotic pathway for the complement factor B-derived fragment Bb J Cell Physiol 185 280 292 11025450
  169. Vyse TJ Kotzin BL 1996 Genetic basis of systemic lupus erythematosus Curr Opin Immunol 8 843 851 8994865
  170. Walker DG McGeer PL 1992 Complement gene expression in human brain: comparison between normal and Alzheimer disease cases Brain Res Mol Brain Res 14 109 116 1323007
  171. Wang Y Rollins SA Madri JA Matis LA 1995 Anti-C5 monoclonal antibody therapy prevents collagen-induced arthritis and ameliorates established disease Proc Natl Acad Sci USA 92 8955 8959 7568051 PMC41086
  172. Webster S Lue LF Brachova L Tenner AJ McGeer PL Terai K Walker DG Bradt B Cooper NR Rogers J 1997 Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimer’s disease Neurobiol Aging 18 415 421 9330973
  173. Weerth SH Rus H Shin ML Raine CS 2003 Complement C5 in experimental autoimmune encephalomyelitis (EAE) facilitates remyelination and prevents gliosis Am J Pathol 163 1069 1080 12937147 PMC1868269
  174. Wingerchuk DM Lucchinetti CF 2007 Comparative immunopathogenesis of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis Curr Opin Neurol 20 343 350 17495631
  175. Wyss-Coray T Yan F Lin AH Lambris JD Alexander JJ Quigg RJ Masliah E 2002 Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer’s mice Proc Natl Acad Sci USA 99 10837 10842 12119423 PMC125059
  176. Yao J Harvath L Gilbert DL Colton CA 1990 Chemotaxis by a CNS macrophage, the microglia J Neurosci Res 27 36 42 2254955
  177. Zalcman S Murray L Dyck DG Greenberg AH Nance DM 1998 Interleukin-2 and -6 induce behavioral-activating effects in mice Brain Res 811 111 121 9804916
  178. Zanjani H Finch CE Kemper C Atkinson J McKeel D Morris JC Price JL 2005 Complement activation in very early Alzheimer disease Alzheimer Dis Assoc Disord 19 55 66 15942322
  179. Zhang X Kimura Y Fang C Zhou L Sfyroera G Lambris JD Wetsel RA Miwa T Song WC 2007 Regulation of Toll-like receptor-mediated inflammatory response by complement in vivo Blood 110 228 236 17363730 PMC1896115
  180. Zhou J Fonseca MI Kayed R Hernandez I Webster SD Yazan O Cribbs DH Glabe CG Tenner AJ 2005 Novel Abeta peptide immunogens modulate plaque pathology and inflammation in a murine model of Alzheimer’s disease J Neuroinflammation 2 28 16332263 PMC1326209
  181. Zhou J Fonseca MI Pisalyaput K Tenner AJ 2008 Complement C3 and C4 expression in C1q sufficient and deficient mouse models of Alzheimer’s disease J Neurochem 106 2080 2092 18624920 PMC2574638

Cited by

Sorted by citations

Authors
Alexander, J. J., Anderson, A. J., Barnum, S. R., Stevens, B., & Tenner, A. J.
Affiliations
  • University of Chicago (US)
  • University of California, Irvine (US)
  • University of Alabama at Birmingham (US)
  • Harvard University (US)
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2008-11-11
Volume
107
Issue
5
Pages
1169-1187
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/j.1471-4159.2008.05668.x
PMC
PMC4038542
OpenAlex
W2078243391
Cited by
177
References
13
Citations by year
2026: 8 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 6 · 2021: 7 · 2020: 10 · 2019: 8 · 2018: 12 · 2017: 17 · 2016: 10 · 2015: 6 · 2014: 14 · 2013: 8 · 2012: 12
FWCI
0.93
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Larry L. Hillblom Foundation
  • National Institute of Neurological Disorders and Stroke (R01NS035144, NS46032, R01NS043428, R01NS046032, NS35144, NS 43428)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
Keywords
complement system, neuroinflammation, neuroprotection, neurodegeneration, complement activation, neurological disorders, central nervous system injury, therapeutic target
MeSH terms
Complement System Proteins, Complement Activation, Humans, Inflammation, Male, Models, Biological, Nervous System Diseases, Yin-Yang

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