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Neuroinflammation, Alzheimer Disease, and Other Aging Disorders

  • Edith G. McGeer
  • Patrick L. McGeer

Neuroinflammation is defined as a localized response to CNS tissue damage. It is characterized by activated microglia attacking the injury source, activated astrocytes limiting the area of involvement, and resident brain cells, including neurons, generating multiple inflammatory mediators. It may expand to involve invasion by leukocytes and serum factors. Studies on Alzheimer disease (AD) over the past two decades have provided much new information about chronic neuroinflammation. This information may have relevance not only to many neurological disorders but also, by extension and with some modification, to such important diseases as atherosclerosis, heart disease, and macular degeneration.

Keywords

Amyotrophic Lateral Sclerosis Alzheimer Disease Membrane Attack Complex Traditional NSAID Alzheimer Disease Brain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Aihara, M., Ishii, S., Kume, K., & Shimizu, T. (2000). Interaction between neurone and microglia mediated by platelet-activating factor. Genes to Cells, 5, 397–406.PubMedCrossRefGoogle Scholar
  2. Aisen, P. S., Schafer, K. A., Grundman, M., Pfeiffer, E., Sano, M., Davis, K. L., et al. (2003). Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. The Journal of the American Medical Association, 289, 2819–2826.CrossRefGoogle Scholar
  3. Aisen, P. S., Schmeidler, J., & Pasinetti, G. M. (2002). Randomized pilot study of nimesulide treatment in Alzheimer's disease. Neurology, 58, 1050–1054.PubMedGoogle Scholar
  4. Akiyama, H., Itagaki, S., & McGeer, P. L. (1988). Major histocompatibility complex antigen expression on rat microglia following epidural kainic acid lesions. Journal of Neuroscience Research, 20, 147–157.PubMedCrossRefGoogle Scholar
  5. Akiyama, H., & McGeer, P. L, (1990). Brain microglia constitutively express b-2 integrins. Journal of Neuroimmunology, 30, 81–93.PubMedCrossRefGoogle Scholar
  6. Alldred, A. (2001). Etanercept in rheumatoid arthritis. Expert Opinion in Pharmacotherapy, 1, 1137–1148.CrossRefGoogle Scholar
  7. Arai, H., Suzuki, T., Sasaki, H., Hanawa, T., Toriizuka, K., & Yamada, H. (2000). A new interventional strategy for Alzheimer's disease by Japanese herbal medicine. Nippon Ronen Igakkai Zasshi-Japanese Journal of Geriatrics, 37, 212–215.PubMedGoogle Scholar
  8. Banati, R. B., Gehrmann, J., Schubert, P., & Kreutzberg, G. W. (1993). Cytotoxicity of microglia. Glia, 7, 111–118.PubMedCrossRefGoogle Scholar
  9. Banati, R. B., Myers, R., & Kreutzberg, G. W. (1997). PK (‘peripheral benzodiazepine’)—binding sites in the CNS indicate early and discrete brain lesions: microautoradiographic detection of [3H]PK11195 binding to activated microglia. Journal of Neurocytology, 26, 77–82.PubMedCrossRefGoogle Scholar
  10. Beneveniste, E. N., Nguyen, V. T., & O'Keefe, G. M. (2001). Immunological aspects of microglia: relevance to Alzheimer's disease. Neurochemistry International, 39, 381–391.CrossRefGoogle Scholar
  11. Biber, K., Dijkstra, I., Trebst, C., De Groot, C. J., Ransohoff, R. M., & Boddeke, H. W. (2002). Functional expression of CXCR3 in cultured mouse and human astrocytes and microglia. Neuroscience, 112, 487–497.PubMedCrossRefGoogle Scholar
  12. Biber, K., Sauter, A., Brouwer, N., Copray, S. C., & Boddeke, H. W. (2001). Ischemia-induced neuronal expression of the microglia attracting chemokine Secondary Lymphoid-tissue Chemokine (SLC). Glia, 34, 121–133.PubMedCrossRefGoogle Scholar
  13. Bodles, A. M., & Barger, S. W. (2005). Secreted beta-amyloid precursor protein activates microglia via JNK and p38-MAPK. Neurobiology of Aging, 26, 9–16.PubMedCrossRefGoogle Scholar
  14. Bok, D. (2005). Evidence for an inflammatory response in age-related mascular degeneration gains new support. Proceedings of the National Academy of Sciences of the United States of America, 102, 7053–70544.PubMedCrossRefGoogle Scholar
  15. Butterfield, D. A., & Kanski, J. (2001). Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mechanisms of Aging and Development, 122, 945–962.CrossRefGoogle Scholar
  16. Chapman, G. A., Moores, K., Harrison, D., Campbell, C. A., Stewart, B. R., & Strijbos, P. J. (2000). Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage. Journal of Neuroscience, 20, RC87.PubMedGoogle Scholar
  17. Cheeran, M. C., Hu, S., Sheng, W. S., Peterson, P. K., & Lokensgard, J. R. (2003). CXCL10 production from cytomegalovirus-stimulated microglia is regulated by both human and viral interleukin-10. Journal of Virology, 77, 4502–4515.PubMedCrossRefGoogle Scholar
  18. Chen, H., Zhang, S. M., Herman, M. A., Schwarzschild, M. A., Willett, W. C., Colditz, G. A., et al. (2003). Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Archives of Neurology, 60, 1059–1064.PubMedCrossRefGoogle Scholar
  19. Colton, C. A., & Gilbert, D. I. (1987). Production of superoxide anions by a CNS macrophage, the microglia. FEBS Letters, 223, 284–288.PubMedCrossRefGoogle Scholar
  20. Columba-Cabezas, S., Serafini, B., Ambrosini, E., Sanchez, M., Penna, G., Adorini, L., et al. (2002). Induction of macrophage-derived chemokine/CCL22 expression in experimental autoimmune encephalomyelitis and cultured microglia: Implications for disease regulation. Journal of Neuroimmunology, 130, 10–21.PubMedCrossRefGoogle Scholar
  21. Cui, Y. H., Le, Y., Gong, W., Proost, P., Van Damme, J., Murphy, W. J., et al. (2002). Bacterial lipopolysaccharide selectively up-regulates the function of the chemotactic peptide receptor formyl peptide receptor 2 in murine microglial cells. Journal of Immunology, 168, 434–442.Google Scholar
  22. Cui, Y., Le, Y., Yazawa, H., Gong, W., & Wang, J. M. (2002). Potential role of the formyl peptide receptor-like 1 (FPRL1) in inflammatory aspects of Alzheimer's disease. Journal of Leukocyte Biology, 72, 628–635.PubMedGoogle Scholar
  23. Cui, Y. H., Le, Y., Zhang, X., Gong, W., Abe, K., Sun, R., et al. (2002). Up-regulation of FPR2, a chemotactic receptor for amyloid beta 1–42 (A beta 42), in murine microglial cells by TNF alpha. Neurobiology of Disease, 10, 366–377.PubMedCrossRefGoogle Scholar
  24. Davis, R. L., & Robertson, D. M. (Eds.). (1991). Textbook of neuropathology (2nd ed.). Baltimore: Williams & Wilkins.Google Scholar
  25. Del Rio Hortega, P. (1919). El ‘tercer elemento’ de los centros nerviosos. Poder fagocitario y movilidad de la microglia. Bol. Soc. Esp. Biol. Ano. ix, 154–166.Google Scholar
  26. De Simone, R., Ajmone-Cat, M. A., & Minghetti, L. (2004). Atypical antiinflammatory activation of microglia induced by apoptotic neurons. Molecular Neurobiology, 19, 197–212.CrossRefGoogle Scholar
  27. Feagan, B. G., Enns, R., Fedorak, R. N., Panaccione, R., Pare, P., Steinhart, A. H., et al. (2001). Infliximab for the treatment of Crohn's disease: Efficacy, safety and pharmacoeconomics. Canadian Journal of Clinical Pharmacology, 8, 188–198.PubMedGoogle Scholar
  28. Finch, C. E. (2005). Developmental origins of aging in brain and blood vessels: An overview. Neurobiology of Aging, 26, 281–291.PubMedCrossRefGoogle Scholar
  29. Firuzi, O., & Pratico, D. (2006). Coxibs and Alzheimer's disease: Should they stay or should they go? Annals of Neurology, 59, 219–228.PubMedCrossRefGoogle Scholar
  30. Flynn, G., Maru, S., Loughlin, J., Romero, I. A., & Male, D. (2003). Regulation of chemokine receptor expression in human microglia and astrocytes. Journal of Neuroimmunology, 136, 84–93.PubMedCrossRefGoogle Scholar
  31. Forstreuter, F., Lucius, R., & Mentlein, R. (2002). Vascular endothelial growth factor induces chemotaxis and proliferation of microglial cells. Journal of Neuroimmunology, 132, 93–98.PubMedCrossRefGoogle Scholar
  32. Gao, H. M., Liu, B., & Hong, J. S. (2003). Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. Journal of Neuroscience, 23, 6181–6187.PubMedGoogle Scholar
  33. Giulian, D., Haverkamp, L. J., Yu, J. H., Harshin, W. L., Li, J., Kirkpatrick, J., et al. (1996). Specific domains of b-amyloid from Alzheimer plaque elicit neuronal killing in human microglia. Journal of Neuroscience, 16, 6021–6037.PubMedGoogle Scholar
  34. Gould, D. J., & Goshgarian, H. G. (1999). The effects of mitotic inhibition on the spinal cord response to the superimposed injuries of spinal cord hemisection and peripheral axotomy. Experimental Neurology, 158, 394–402.PubMedCrossRefGoogle Scholar
  35. Hamilton, K., & Clair, E. W. (2000). Tumour necrosis factor-alpha blockade: A new era for the effective management of rheumatoid arthritis. Expert Opinion in Pharmacotherapy, 1, 1041–1052.CrossRefGoogle Scholar
  36. Haymaker, W., & Adams, R. D. (Eds.), (1982). Histology and histopathology of the nervous system. Springfield, IL: Charles C Thomas.Google Scholar
  37. Heneka, M. T., Sastre, M., Dumitrescu-Ozimek, L., Hanke, A., Dewachter, I., Kuiperi, C., et al. (2005). Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1–42 levels in APPV717I transgenic mice. Brain, 128, 1442–1453.PubMedCrossRefGoogle Scholar
  38. Henkel, J. S., Engelhardt, J. I., Siklos, L., Simpson, E. P., Kim, S. H., Pan, T., et al. (2004). Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Annals of Neurology, 55, 221–235.PubMedCrossRefGoogle Scholar
  39. Honda, S., Sasaki, Y., Ohsawa, K., Imai, Y., Nakamura, Y., Inoue, K., et al. (2001). Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. Journal of Neuroscience, 21, 1975–1982.PubMedGoogle Scholar
  40. Hurley, S. D., & Coleman, P. D. (2003). Facial nerve axotomy in aged and young adult rats: analysis of the glial response. Neurobiology of Aging, 24, 511–518.PubMedCrossRefGoogle Scholar
  41. Jantzen, P. T., Connor, K. E., DiCarlo, G., Wenk, G. L., Wallace, J. L., Rojiani, A. M., et al. (2002). Microglial activation and beta-amyloid deposit reduction caused by a nitric oxide-releasing nonsteroidal anti-inflammatory drug in amyloid precursor protein plus presenilin-1 transgenic mice. Journal of Neuroscience, 22, 2246–2254.PubMedGoogle Scholar
  42. Johnstone, M., Gearing, A. J., & Miller, K. M. (1999). A central role for astrocytes in the inflammatory response to beta-amyloid; chemokines, cytokines and reactive oxygen species are produced. Journal of Neuroimmunology, 93, 182–193.PubMedCrossRefGoogle Scholar
  43. Kawamata, T., Akiyama, H., Yamada, T., & McGeer, P. L. (1992). Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. American Journal of Pathology, 140, 691–707.PubMedGoogle Scholar
  44. Keller, J. N., Mark, R. J., Bruce, A. J., Blanc, E., Rothstein, J. D., Uchida, K., et al. (1997). 4-Hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes. Neuroscience, 80, 685–696.PubMedCrossRefGoogle Scholar
  45. Klegeris, A., Bissonnette, C. J., & McGeer, P. L. (2005). Modulation of human microglia and THP-1 cell toxicity by cytokines endogenous to the nervous system. Neurobiology of Aging, 26, 673–682.PubMedCrossRefGoogle Scholar
  46. Klegeris, A., & McGeer, P. L. (1994). Rat brain microglia and peritoneal macrophages show similar responses to respiratory burst stimulants. Journal of Neuroimmunology, 53, 83–90.PubMedCrossRefGoogle Scholar
  47. Klegeris, A., & McGeer, P. L. (2000). Interaction of various intrasignalling mechanisms involved in mononuclear phagocyte toxicity towards neuronal cells. Journal of Leukocyte Biology, 67, 127–133.PubMedGoogle Scholar
  48. Klegeris, A., & McGeer, P. L. (2005). Non-steroidal antiinflammatory drugs (NSAIDs) and other antiinflammatory agents in the treatment of neurodegenerative disease. Current Alzheimer Research, 2, 355–365.PubMedCrossRefGoogle Scholar
  49. Klegeris, A., Walker, D. G., & McGeer, P. L. (1997). Regulation of glutamate in cultures of human monocytic THP-1 and astrocytoma U-373 MG cells. Journal of Neuroimmunology, 78, 152–161.PubMedCrossRefGoogle Scholar
  50. Koistinaho, M., & Koistinaho, J. (2002). Role of p38 and p44/42 mitogen-activated protein kinases in microglia. Glia, 40, 175–183.PubMedCrossRefGoogle Scholar
  51. Krogsgaard, M., Wucherpfennig, K. W., Cannella, B., Hansen, B. E., Svejgaard, A., Pyrdol, J., et al. (2000). Visualization of myelin basic protein (MBP) T cell epitopes in multiple sclerosis lesions using a monoclonal antibody specific for the human histocompatibility leukocyte antigen (HLA)-DR2-MBP 85–99 complex. Journal of Experimental Medicine, 191, 1395–1412.PubMedCrossRefGoogle Scholar
  52. Kuehn, B. M. (2005). Inflammation suspected in eye disorders. The Journal of American Medical Association, 294, 31–32.CrossRefGoogle Scholar
  53. Lauderback, C. M., Hackett, J. M., Huang, F. F., Keller, J. N., Szweda, L. I., Markesbery, W. R., et al. (2001). The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer's disease brain: The role of A beta 1–42. Journal of Neurochemistry, 78, 413–416.PubMedCrossRefGoogle Scholar
  54. Lim, G. P., Yang, F., Chu, T., Chen, P., Beech, W., Teter, B., et al. (2000). Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. Journal of Neuroscience, 20, 5709–5714.PubMedGoogle Scholar
  55. Luber-Narod, J., & Rogers, J. (1988). Immune system associated antigens expressed by cells of the human central nervous system. Neuroscience Letters, 94, 265–273.Google Scholar
  56. Lue, L. F., Walker, D. G., Brachova, L., Beach, T. G., Rogers, J., Schmidt, A. M., et al. (2001). Involvement of microglial receptor for advanced glycation endproducts (RAGE) in Alzheimer's disease: Identification of a cellular activation mechanism. Experimental Neurology, 171, 29–45.PubMedCrossRefGoogle Scholar
  57. Martin, S., Vincent, J. P. & Mazella, J. (2003). Involvement of the neurotensin receptor-3 in the neurotensin-induced migration of human microglia. Journal of Neuroscience, 23, 1198–1205.PubMedGoogle Scholar
  58. Mattsson, P., Aldskogius, H., & Svensson, M. (1999). Nimodipine-induced improved survival rate of facial motor neurons following intracranial transection of the facial nerve in the adult rat. Journal of Neurosurgery, 90, 760–765.PubMedCrossRefGoogle Scholar
  59. McDonald, D. R., Brunden, K. R., & Landreth, G. E. (1997). Amyloid fibrils activate tyrosine kinase-dependent signaling and superoxide production in microglia. Journal of Neuroscience, 17, 2284–2294.PubMedGoogle Scholar
  60. McGeer, P. L., Akiyama, H., Kawamata, T., Yamada, T., Walker, D. G., & Ishii, T. (1992). Immunohistochemical localization of beta-amyloid precursor protein sequences in Alzheimer and normal brain tissue by light and electron microscopy. Journal of Neuroscience Research, 31, 428–442.PubMedCrossRefGoogle Scholar
  61. McGeer, P. L., Itagaki, S., Boyes, B. E., & McGeer, E. G. (1988). Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology, 38, 1285–1291.PubMedGoogle Scholar
  62. McGeer, P. L., Itagaki, S., & McGeer, E. G. (1988). Expression of the histocompatibility glycoprotein HLA-DR in neurological disease. Acta Neuropathology, 76, 550–557.CrossRefGoogle Scholar
  63. McGeer, P. L., & McGeer, E. G. (1995). The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative disease. Brain Research Reviews, 21, 195–218.PubMedCrossRefGoogle Scholar
  64. McGeer, P. L., & McGeer, E. G. (2001). Inflammation, autotoxicity and Alzheimer disease. Neurobiology of Aging, 22, 799–809.PubMedCrossRefGoogle Scholar
  65. McGeer, P. L., & McGeer, E. G. (2004a). Inflammation and the degenerative diseases of aging. Annals of the New York Academy of Science, 1035, 104–116.CrossRefGoogle Scholar
  66. McGeer, P. L., & McGeer, E. G. (2004b). Inflammation and neurodegeneration in Parkinson's disease. Parkinsonism and Related Disorders, 10, S3–S7.PubMedCrossRefGoogle Scholar
  67. McGeer, P. L. & Sibley, J. (2005). Sparing of age-related macular degeneration in rheumatoid arthritis. Neurobiology of Aging, 26, 1199–1203.PubMedCrossRefGoogle Scholar
  68. McGeer, E. G., Yasojima, K., Schwab, C., & McGeer, P. L. (2001). The pentraxins: possible role in Alzheimer's disease and other innate inflammatory disorders. Neurobiology of Aging, 22, 843–848.PubMedCrossRefGoogle Scholar
  69. McMillan, M. K., Vainio, P. J., & Tuominen, R. K. (1997). Role of protein kinase C in microglia-induced neurotoxicity in mesencephalic cultures. Journal of Neuropathology and Experimental Neurology, 56, 301–307.CrossRefGoogle Scholar
  70. Metchnikoff, E. (1892). Lecons sur la pathologie comparée de l'inflammation. Paris: Masson.Google Scholar
  71. Mosser, D. M. (2003). The many faces of macrophage activation. Journal of Leukocyte Biology, 73, 209–212.PubMedCrossRefGoogle Scholar
  72. Mueller, C. A., Richt, J. A., Meyermann, R., Deininger, M., & Schluesener, H. (2003). Accumulation of the proinflammatory cytokine endothelial-monocyte-activating polypeptide II in ramified microglial cells in brains of Borna virus infected Lewis rats. Neuroscience Letters, 339, 215–218.PubMedCrossRefGoogle Scholar
  73. Nakai, M., Tanimukai, S., Yagi, K., Saito, N., Taniguchi, T., Terashima, A., et al. (2001). Amyloid beta protein activates PKC-delta and induces translocation of myristoylated alanine-rich C kinase substrate (MARCKS) in microglia. Neurochemistry International, 38, 593–600.PubMedCrossRefGoogle Scholar
  74. Neuroinflammation Working Group. (2000). Inflammation and Alzheimer's disease. Neurobiology of Aging, 21, 383–421.CrossRefGoogle Scholar
  75. Nolan, Y., Martin, D., Campbell, V. A., & Lynch, M. A. (2004). Evidence of a protective effect of phosphatidyl-containing liposojmes on lipopolysaccharide-induced impairment of long-term potentiation in the rat hippocampus. Journal of Neurobiology, 151, 12–23.Google Scholar
  76. Nolte, C., Kirchhoff, F., & Kettenmann, H. (1997). Epidermal growth factor is a motility factor for microglial cells in vitro: Evidence for EGF receptor expression. European Journal of Neuroscience, 9, 1690–1698.PubMedCrossRefGoogle Scholar
  77. Pelaez, B., Blazquez, J. L., Pastor, F. E., Sanchez, A., & Amat, P. (1999). Lectin histochemistry and ultrastructure of microglial response to monosodium glutamate-mediated neurotoxicity in the arcuate nucleus. Histology and Histopathology, 14, 165–174.PubMedGoogle Scholar
  78. Penfield, W. (1925). Microglia and the process of phagocytosis in gliomas. American Journal of Pathology, 1, 77–89.PubMedGoogle Scholar
  79. Pereira, H. A., Ruan, X., & Kumar, P. (2003). Activation of microglia: a neuroinflammatory role for CAP37. Glia, 41, 64–72.PubMedCrossRefGoogle Scholar
  80. Pocock, J. M., Liddle, A. C., Hooper, C., Taylor, D. L., Davenport, C. M., & Morgan, S. C. (2002). Activated microglia in Alzheimer's disease and stroke. Ernst Schering Foundation Workshop, 39, 105–132.Google Scholar
  81. Prat, E., Baron, P., Meda, L., Scarpini, E., Galimberti, D., Ardolino, G., et al. (2000). The human astrocytoma cell line U373MG produces monocyte chemotactic protein (MCP)-1 upon stimulation with beta-amyloid protein. Neuroscience Letters, 283, 177–180.PubMedCrossRefGoogle Scholar
  82. Quigg, R. J., 2002. Use of complement inhibitors in tissue injury. Trends in Molecular Medicine, 9, 430–437.CrossRefGoogle Scholar
  83. Quinn, J., Montine, T., Morrow, J., Woodward, W. R., Kulhanek, D., & Eckenstein, F. (2003). Inflammation and cerebral amyloidosis are disconnected in an animal model of Alzheimer's disease. Journal of Neuroimmunology, 137, 32–41.PubMedCrossRefGoogle Scholar
  84. Rappert, A., Biber, K., Nolte, C., Lipp, M., Schubel, A., Lu, B., et al. (2002). Secondary lymphoid tissue chemokine (CCL21) activates CXCR3 to trigger a Cl- current and chemotaxis in murine microglia. Journal of Immunology, 168, 3221–3226.Google Scholar
  85. Reid, D. M., Perry, V. H., Andersson, P. B., & Gordon, S. (1993). Mitosis and apoptosis of microglia in vivo induced by an anti-CR3 antibody which crosses the blood-brain barrier. Neuroscience, 56, 529–533.PubMedCrossRefGoogle Scholar
  86. Reines, S. A., Block, G. A., Morris, J. C., Liu, G., Nessly, M. L., Lines, C. R., et al. (2004). Rofecoxib: No effect on Alzheimer's disease in a 1-year, randomized, blinded, controlled study. Neurology, 62, 66–71.PubMedGoogle Scholar
  87. Rezaie, P., Trillo-Pazos, G., Greenwood, J., Everall, I. P. & Male, D. K. (2002). Motility and ramification of human fetal microglia in culture: An investigation using time-lapse video microscopy and image analysis. Experimental Cell Research, 274, 68–82.PubMedCrossRefGoogle Scholar
  88. Righi, M., Letari, O., Sacerdote, P., Marangoni, F., Miozzo, A., & Nicosia, S. (1995). Myc-immortalized microglial cells express a functional platelet-activating factor receptor. Journal of Neurochemistry, 64, 121–129.PubMedCrossRefGoogle Scholar
  89. Ringheim, G. E. (1995). Mitogenic effects of interleukin-5 on microglia. Neuroscience Letters, 201, 131–134.PubMedCrossRefGoogle Scholar
  90. Rogers, J., Kirby, L. C., Hempelman, S. R., Berry, D. L., McGeer, P. L., Kaszniak, A. W., et al. (1993). Clinical trial of indomethacin in Alzheimer's disease. Neurology, 43, 1609–1611.PubMedGoogle Scholar
  91. Rogers, J., Webster, S., Schultz, J., McGeer, P. L., Styren, S., Civin, W. H., et al. (1992). Complement activation by b-amyloid in Alzheimer disease. Proceedings of the. National Academy of Science of the United States of America, 89, 10016–10020.CrossRefGoogle Scholar
  92. Ruan, R. S., Leong, S. K., & Yeoh, K. H. (1994). Glial reaction after facial nerve compression in the facial canal of the albino rat. Acta Oto-Laryngologica, 114, 271–277.PubMedCrossRefGoogle Scholar
  93. Sainati, S. M., Ingram, D. M., Talwalker, S., & Geis, G. S. (2000). Results of a double-blind, placebo-controlled study of celecoxib for the progression of Alzheimer's disease. Sixth International Stockholm-Springfield Symposium of Advances in Alzheimer Therapy, 180.Google Scholar
  94. Scharf, S., Mander, A., Ugoni, A., Vajda, F., & Christophidis, N. (1999). A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease. Neurology, 53, 197–201.PubMedGoogle Scholar
  95. Scholl, H. P., Weber, B. H., Nothen, M. M., Wienker, T., & Holz, F. G. (2005). Y402H polymorphism in complement factor H and age-related macular degeneration (AMD). Ophthalmology, 102, 1029–1035.CrossRefGoogle Scholar
  96. Schwab, C., Hosokawa, M., & McGeer, P. L. (2004). Transgenic mice overexpressing amyloid beta-protein are an incomplete model of Alzheimer disease. Experimental Neurology, 188, 52–64.PubMedCrossRefGoogle Scholar
  97. Shepherd, C. E., Gregory, G. C., Vickers, J. C., & Halliday, G. M. (2005). Novel ‘inflammatory plaque’ pathology in presenilin-1 Alzheimer's disease. Neuropathology and Applied Neurobiology, 31, 503–511.PubMedCrossRefGoogle Scholar
  98. Soriano, S. G., Amaravadi, L. S., Wang, Y. F., Zhou, H., Yu, G. X., Tonra, J. R., et al. (2002). Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury. Journal of Neuroimmunology, 125, 59–65.PubMedCrossRefGoogle Scholar
  99. Sugiura, S., Lahav, R., Han, J., Kou, S. Y., Banner, L. R., de Pablo, F., et al. (2000). Leukaemia inhibitory factor is required for normal inflammatory responses to injury in the peripheral and central nervous systems in vivo and is chemotactic for macrophages in vitro. European Journal of Neuroscience, 12, 457–466.PubMedCrossRefGoogle Scholar
  100. Szczepanik, A. M., Funes, S., Petko, W., & Ringheim, G. E. (2001). IL-4, IL-10 and IL-13 modulate Ab(1–42)-induced cytokine and chemokine production in primary murine microglia and a human monocyte cell line. Journal of Neuroimmunology, 113, 49–62.PubMedCrossRefGoogle Scholar
  101. Tiffany, H. L., Lavigne, M. C., Cui, Y. H., Wang, J. M., Leto, T. L., Gao, J. L., et al. (2001). Amyloid-beta induces chemotaxis and oxidant stress by acting at formylpeptide receptor 2, a G protein-coupled receptor expressed in phagocytes and brain. Journal of Biological Chemistry, 276, 23645–23652.PubMedCrossRefGoogle Scholar
  102. Van Furth, R. (1982). Current view on the mononuclear phagocyte system. Immunobiology, 161, 178–185.PubMedGoogle Scholar
  103. van Groen, T., & Kadish, I. (2005). Transgenic AD model mice, effects of potential anti-AD treatments on inflammation and pathology. Brain Research Reviews, 48, 370–378.PubMedCrossRefGoogle Scholar
  104. Waetzig, V., Czeloth, K., Hidding, U., Mielke, K., Kanzow, M., Brecht, S., et al. (2005). c-Jun N-terminal kinases (JNKs) mediate pro-inflammatory actions of microglia. Glia, 50, 235–246.PubMedCrossRefGoogle Scholar
  105. Wang, J., Crawford, K., Yuan, M., Wang, H., Gorry, P. R., & Gabuzda, D. (2002). Regulation of CC chemokine receptor 5 and CD4 expression and human immunodeficiency virus type 1 replication in human macrophages and microglia by T helper type 2 cytokines. Journal of Infectious Diseases, 185, 885–897.PubMedCrossRefGoogle Scholar
  106. Webster, S., Lue, L. F., Brachova, L., Tenner, A. J., McGeer, P. L., Terai, K., et al. (1997). Molecular and cellular characterization of the membrane attack complex, C5b–9, in Alzheimer's disease. Neurobiology of Aging, 18, 415–421.PubMedCrossRefGoogle Scholar
  107. Williamson, K. S., Gabbita, S. P., Mou, S., West, M., Pye, Q. N., Markesbery, W. R., et al. (2002). The nitration product 5-nitro-gamma-tocopherol is increased in the Alzheimer brain. Nitric Oxide, 6, 221–227.PubMedCrossRefGoogle Scholar
  108. Wirjatijasa, F., Dehghani, F., Blaheta, R. A., Korf, H. W., & Hailer, N. P. (2002). Interleukin-4, interleukin-10, and interleukin-1 receptor antagonist but not transforming growth factor-beta induce ramification and reduce adhesion molecule expression of rat microglial cells. Journal of Neuroscience Research, 68, 579–587.PubMedCrossRefGoogle Scholar
  109. Wisniewski, H. M., Vorbrodt, A. W., Wegiel, J., Morys, J., & Lossinsky, A. S. (1990). Ultrastructure of the cells forming amyloid fibers in Alzheimer disease and scrapie. American Journal of Medical Genetics-Supplement, 7, 287–297.PubMedGoogle Scholar
  110. Yan, Q., Zhang, J., Liu, H., Babu-Khan, S., Vassar, R., Biere, A. L., et al. (2003). Anti-inflammatory drug therapy alters beta-amyloid processing and deposition in an animal model of Alzheimer's disease. Journal of Neuroscience, 23, 7504–7509.PubMedGoogle Scholar
  111. Yasojima, K., Schwab, C., McGeer, E. G., & McGeer, P. L. (1999). Distribution of cyclooxygenase-1 and cyclooxygenase-2 mRNAs and proteins in human brain and peripheral organs. Brain Research, 830, 226–236.PubMedCrossRefGoogle Scholar
  112. Yoshida, S., Yoshida, A., Ishibashi, T., Elner, S. G., & Elner, V. M. (2003). Role of MCP-1 and MIP-1alpha in retinal neovascularization during postischemic inflammation in a mouse model of retinal neovascularization. Journal of Leukocyte Biology, 73, 137–144.PubMedCrossRefGoogle Scholar
  113. Yuan, L., & Neufeld, A. H. (2001). Activated microglia in the human glaucomatous optic nerve head. Journal of Neuroscience Research, 64, 523–532.PubMedCrossRefGoogle Scholar
  114. Ziaja, M., & Janeczko, K. (1999). Spatiotemporal patterns of microglial proliferation in rat brain injured at the postmitotic stage of postnatal development. Journal of Neuroscience Research, 58, 379–378.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Edith G. McGeer
    • 1
  • Patrick L. McGeer
    • 1
  1. 1.Kinsmen Laboratory of Neurological ResearchUniversity of British ColumbiaVancouverCanada

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