Molecular Neurobiology

, Volume 41, Issue 2–3, pp 232–241

Astrogliosis in CNS Pathologies: Is There A Role for Microglia?

  • Dan Zhang
  • Xiaoming Hu
  • Li Qian
  • James P. O’Callaghan
  • Jau-Shyong Hong
Article

Abstract

Astrogliosis, a cellular reaction with specific structural and functional characteristics, represents a remarkably homotypic response of astrocytes to all kinds of central nervous system (CNS) pathologies. Astrocytes play diverse functions in the brain, both harmful and beneficial. Mounting evidence indicates that astrogliosis is an underlying component of a diverse range of diseases and associated neuropathologies. The mechanisms that lead to astrogliosis are not fully understood, nevertheless, damaged neurons have long been reported to induce astrogliosis and astrogliosis has been used as an index for underlying neuronal damage. As the predominant source of proinflammatory factors in the CNS, microglia are readily activated under certain pathological conditions. An increasing body of evidence suggests that release of cytokines and other soluble products by activated microglia can significantly influence the subsequent development of astrogliosis and scar formation in CNS. It is well known that damaged neurons activate microglia very quickly, therefore, it is possible that activated microglia contribute factors/mediators through which damaged neuron induce astrogliosis. The hypothesis that activated microglia initiate and maintain astrogliosis suggests that suppression of microglial overactivation might effectively attenuate reactive astrogliosis. Development of targeted anti-microglial activation therapies might slow or halt the progression of astrogliosis and, therefore, help achieve a more beneficial environment in various CNS pathologies.

Keywords

Astrocyte GFAP Astrogliosis Microglia Cytokine 

References

  1. 1.
    Malarkey EB, Parpura V (2008) Mechanisms of glutamate release from astrocytes. Neurochem Int 52:142–154PubMedCrossRefGoogle Scholar
  2. 2.
    Bergami M, Santi S, Formaggio E, Cagnoli C, Verderio C, Blum R, Berninger B, Matteoli M, Canossa M (2008) Uptake and recycling of pro-BDNF for transmitter-induced secretion by cortical astrocytes. J Cell Biol 183:213–221PubMedCrossRefGoogle Scholar
  3. 3.
    Bogen IL, Risa O, Haug KH, Sonnewald U, Fonnum F, Walaas SI (2008) Distinct changes in neuronal and astrocytic amino acid neurotransmitter metabolism in mice with reduced numbers of synaptic vesicles. J Neurochem 105:2524–2534PubMedCrossRefGoogle Scholar
  4. 4.
    Araque A (2008) Astrocytes process synaptic information. Neuron Glia Biol 4:3–10PubMedCrossRefGoogle Scholar
  5. 5.
    Hu R, Cai WQ, Wu XG, Yang Z (2007) Astrocyte-derived estrogen enhances synapse formation and synaptic transmission between cultured neonatal rat cortical neurons. Neuroscience 144:1229–1240PubMedCrossRefGoogle Scholar
  6. 6.
    Ishibashi T, Dakin KA, Stevens B, Lee PR, Kozlov SV, Stewart CL, Fields RD (2006) Astrocytes promote myelination in response to electrical impulses. Neuron 49:823–832PubMedCrossRefGoogle Scholar
  7. 7.
    Yamaguchi H, Kidachi Y, Umetsu H, Ryoyama K (2008) Differentiation of serum-free mouse embryo cells into an astrocytic lineage is associated with the asymmetric production of early neural, neuronal and glial markers. Biol Pharm Bull 31:1008–1012PubMedCrossRefGoogle Scholar
  8. 8.
    Bundesen LQ, Scheel TA, Bregman BS, Kromer LF (2003) Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. J Neurosci 23:7789–7800PubMedGoogle Scholar
  9. 9.
    Petros TJ, Williams SE, Mason CA (2006) Temporal regulation of EphA4 in astroglia during murine retinal and optic nerve development. Mol Cell Neurosci 32:49–66PubMedCrossRefGoogle Scholar
  10. 10.
    Eng LF, Ghirnikar RS (1994) GFAP and astrogliosis. Brain Pathol 4:229–237PubMedCrossRefGoogle Scholar
  11. 11.
    Guo Y, Liu Y, Xu L, Wu S, Yang C, Wu D, Wu H, Li C (2007) Astrocytic pathology in the immune-mediated motor neuron injury. Amyotroph Lateral Scler 8:230–234PubMedCrossRefGoogle Scholar
  12. 12.
    Pannu R, Singh AK, Singh I (2005) A novel role of lactosylceramide in the regulation of tumor necrosis factor alpha-mediated proliferation of rat primary astrocytes. Implications for astrogliosis following neurotrauma. J Biol Chem 280:13742–13751PubMedCrossRefGoogle Scholar
  13. 13.
    Reinhard JF Jr, Miller DB, O’Callaghan JP (1988) The neurotoxicant MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) increases glial fibrillary acidic protein and decreases dopamine levels of the mouse striatum: evidence for glial response to injury. Neurosci Lett 95:246–251PubMedCrossRefGoogle Scholar
  14. 14.
    Zhang L, Zhang WP, Chen KD, Qian XD, Fang SH, Wei EQ (2007) Caffeic acid attenuates neuronal damage, astrogliosis and glial scar formation in mouse brain with cryoinjury. Life Sci 80:530–537PubMedCrossRefGoogle Scholar
  15. 15.
    O’Callaghan JP (1991) Assessment of neurotoxicity: use of glial fibrillary acidic protein as a biomarker. Biomed Environ Sci 4:197–206PubMedGoogle Scholar
  16. 16.
    O’Callaghan JP (1994) Biochemical analysis of glial fibrillary acidic protein as a quantitative approach to neurotoxicity assessment: advantages, disadvantages and application to the assessment of NMDA receptor antagonist-induced neurotoxicity. Psychopharmacol Bull 30:549–554PubMedGoogle Scholar
  17. 17.
    O’Callaghan JP, Jensen KF (1992) Enhanced expression of glial fibrillary acidic protein and the cupric silver degeneration reaction can be used as sensitive and early indicators of neurotoxicity. Neurotoxicology 13:113–122PubMedGoogle Scholar
  18. 18.
    O’Callaghan JP, Sriram K (2005) Glial fibrillary acidic protein and related glial proteins as biomarkers of neurotoxicity. Expert Opin Drug Saf 4:433–442PubMedCrossRefGoogle Scholar
  19. 19.
    Peretto P, Merighi A, Fasolo A, Bonfanti L (1997) Glial tubes in the rostral migratory stream of the adult rat. Brain Res Bull 42:9–21PubMedCrossRefGoogle Scholar
  20. 20.
    Wang K, Bekar LK, Furber K, Walz W (2004) Vimentin-expressing proximal reactive astrocytes correlate with migration rather than proliferation following focal brain injury. Brain Res 1024:193–202PubMedCrossRefGoogle Scholar
  21. 21.
    Herrmann JE, Imura T, Song B, Qi J, Ao Y, Nguyen TK, Korsak RA, Takeda K, Akira S, Sofroniew MV (2008) STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 28:7231–7243PubMedCrossRefGoogle Scholar
  22. 22.
    Zhu Z, Zhang Q, Yu Z, Zhang L, Tian D, Zhu S, Bu B, Xie M, Wang W (2007) Inhibiting cell cycle progression reduces reactive astrogliosis initiated by scratch injury in vitro and by cerebral ischemia in vivo. Glia 55:546–558PubMedCrossRefGoogle Scholar
  23. 23.
    Araque A, Carmignoto G, Haydon PG (2001) Dynamic signaling between astrocytes and neurons. Annu Rev Physiol 63:795–813PubMedCrossRefGoogle Scholar
  24. 24.
    Malhotra SK, Luong LT, Bhatnagar R, Shnitka TK (1997) Up-regulation of reactive astrogliosis in the rat glioma 9 L cell line by combined mechanical and chemical injuries. Cytobios 89(357):115–134PubMedGoogle Scholar
  25. 25.
    Wakasa S, Shiiya N, Tachibana T, Ooka T, Matsui Y (2009) A semiquantitative analysis of reactive astrogliosis demonstrates its correlation with the number of intact motor neurons after transient spinal cord ischemia. J Thorac Cardiovasc Surg 137(4):983–990PubMedCrossRefGoogle Scholar
  26. 26.
    Okamoto M, Wang X, Baba M (2005) HIV-1-infected macrophages induce astrogliosis by SDF-1alpha and matrix metalloproteinases. Biochem Biophys Res Commun 336(4):1214–1220PubMedCrossRefGoogle Scholar
  27. 27.
    Sofroniew MV (2009) Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 32(12):638–647PubMedCrossRefGoogle Scholar
  28. 28.
    El-Fawal HA, O’Callaghan JP (2008) Autoantibodies to neurotypic and gliotypic proteins as biomarkers of neurotoxicity: assessment of trimethyltin (TMT). Neurotoxicology 29(1):109–115PubMedCrossRefGoogle Scholar
  29. 29.
    Norenberg MD, Rao KV, Jayakumar AR (2005) Mechanisms of ammonia-induced astrocyte swelling. Metab Brain Dis 20:303–318PubMedCrossRefGoogle Scholar
  30. 30.
    Norton WT, Aquino DA, Hozumi I, Chiu FC, Brosnan CF (1992) Quantitative aspects of reactive gliosis: a review. Neurochem Res 17:877–885PubMedCrossRefGoogle Scholar
  31. 31.
    Oppenheim RW, Houenou LJ, Parsadanian AS, Prevette D, Snider WD, Shen L (2000) Glial cell line-derived neurotrophic factor and developing mammalian motoneurons: regulation of programmed cell death among motoneuron subtypes. J Neurosci 20:5001–5011PubMedGoogle Scholar
  32. 32.
    Zhao Z, Alam S, Oppenheim RW, Prevette DM, Evenson A, Parsadanian A (2004) Overexpression of glial cell line-derived neurotrophic factor in the CNS rescues motoneurons from programmed cell death and promotes their long-term survival following axotomy. Exp Neurol 190:356–372PubMedCrossRefGoogle Scholar
  33. 33.
    Struzynska L (2009) A glutamatergic component of lead toxicity in adult brain: the role of astrocytic glutamate transporters. Neurochem Int 55:151–156PubMedCrossRefGoogle Scholar
  34. 34.
    Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN, Mucke L, Johnson MH, Sofroniew MV (1999) Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 23:297–308PubMedCrossRefGoogle Scholar
  35. 35.
    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 24:2143–2155PubMedCrossRefGoogle Scholar
  36. 36.
    Myer DJ, Gurkoff GG, Lee SM, Hovda DA, Sofroniew MV (2006) Essential protective roles of reactive astrocytes in traumatic brain injury. Brain 129:2761–2772PubMedCrossRefGoogle Scholar
  37. 37.
    Weiss N, Miller F, Cazaubon S, Couraud PO (2009) The blood-brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta 1788:842–857PubMedCrossRefGoogle Scholar
  38. 38.
    Igarashi Y, Utsumi H, Chiba H, Yamada-Sasamori Y, Tobioka H, Kamimura Y, Furuuchi K, Kokai Y, Nakagawa T, Mori M, Sawada N (1999) Glial cell line-derived neurotrophic factor induces barrier function of endothelial cells forming the blood-brain barrier. Biochem Biophys Res Commun 261:108–112PubMedCrossRefGoogle Scholar
  39. 39.
    Haseloff RF, Blasig IE, Bauer HC, Bauer H (2005) In search of the astrocytic factor(s) modulating blood-brain barrier functions in brain capillary endothelial cells in vitro. Cell Mol Neurobiol 25(1):25–39PubMedCrossRefGoogle Scholar
  40. 40.
    Privat A (2003) Astrocytes as support for axonal regeneration in the central nervous system of mammals. Glia 43:91–93PubMedCrossRefGoogle Scholar
  41. 41.
    Cafferty WB, Yang SH, Duffy PJ, Li S, Strittmatter SM (2007) Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans. J Neurosci 27:2176–2185PubMedCrossRefGoogle Scholar
  42. 42.
    Rolls A, Shechter R, Schwartz M (2009) The bright side of the glial scar in CNS repair. Nat Rev Neurosci 10:235–241PubMedCrossRefGoogle Scholar
  43. 43.
    Menet V, Prieto M, Privat A, Gimenez y Ribotta M (2003) Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes. Proc Natl Acad Sci USA 100:8999–9004PubMedCrossRefGoogle Scholar
  44. 44.
    Wilhelmsson U, Li L, Pekna M, Berthold CH, Blom S, Eliasson C, Renner O, Bushong E, Ellisman M, Morgan TE, Pekny M (2004) Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J Neurosci 24:5016–5021PubMedCrossRefGoogle Scholar
  45. 45.
    Oleszak EL, Zaczynska E, Bhattacharjee M, Butunoi C, Legido A, Katsetos CD (1998) Inducible nitric oxide synthase and nitrotyrosine are found in monocytes/macrophages and/or astrocytes in acute, but not in chronic, multiple sclerosis. Clin Diagn Lab Immunol 5:438–445PubMedGoogle Scholar
  46. 46.
    Estevez AG, Spear N, Manuel SM, Radi R, Henderson CE, Barbeito L, Beckman JS (1998) Nitric oxide and superoxide contribute to motor neuron apoptosis induced by trophic factor deprivation. J Neurosci 18:923–931PubMedGoogle Scholar
  47. 47.
    Bezzi P, Domercq M, Brambilla L, Galli R, Schols D, De Clercq E, Vescovi A, Bagetta G, Kollias G, Meldolesi J, Volterra A (2001) CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity. Nat Neurosci 4:702–710PubMedCrossRefGoogle Scholar
  48. 48.
    Chauhan VS, Sterka DG Jr, Gray DL, Bost KL, Marriott I (2008) Neurogenic exacerbation of microglial and astrocyte responses to Neisseria meningitidis and Borrelia burgdorferi. J Immunol 180:8241–8249PubMedGoogle Scholar
  49. 49.
    Khurgel M, Ivy GO (1996) Astrocytes in kindling: relevance to epileptogenesis. Epilepsy Res 26:163–175PubMedCrossRefGoogle Scholar
  50. 50.
    Miyazaki T, Miyamoto O, Janjua NA, Hata T, Takahashi F, Itano T (2003) Reactive gliosis in areas around third ventricle in association with epileptogenesis in amygdaloid-kindled rat. Epilepsy Res 56:5–15PubMedCrossRefGoogle Scholar
  51. 51.
    Lycke JN, Karlsson JE, Andersen O, Rosengren LE (1998) Neurofilament protein in cerebrospinal fluid: a potential marker of activity in multiple sclerosis. J Neurol Neurosurg Psychiatry 64:402–404PubMedCrossRefGoogle Scholar
  52. 52.
    Canton T, Pratt J, Stutzmann JM, Imperato A, Boireau A (1998) Glutamate uptake is decreased tardively in the spinal cord of FALS mice. NeuroReport 9:775–778PubMedCrossRefGoogle Scholar
  53. 53.
    Ferri A, Nencini M, Casciati A, Cozzolino M, Angelini DF, Longone P, Spalloni A, Rotilio G, Carri MT (2004) Cell death in amyotrophic lateral sclerosis: interplay between neuronal and glial cells. Faseb J 18:1261–1263PubMedGoogle Scholar
  54. 54.
    Sabri F, Titanji K, De Milito A, Chiodi F (2003) Astrocyte activation and apoptosis: their roles in the neuropathology of HIV infection. Brain Pathol 13:84–94PubMedCrossRefGoogle Scholar
  55. 55.
    Sporer B, Missler U, Magerkurth O, Koedel U, Wiesmann M, Pfister HW (2004) Evaluation of CSF glial fibrillary acidic protein (GFAP) as a putative marker for HIV-associated dementia. Infection 32:20–23PubMedCrossRefGoogle Scholar
  56. 56.
    Hayakawa T, Ushio Y, Mori T, Arita N, Yoshimine T, Maeda Y, Shimizu K, Myoga A (1979) Levels in stroke patients of CSF astroprotein, an astrocyte-specific cerebroprotein. Stroke 10:685–689PubMedGoogle Scholar
  57. 57.
    Kernie SG, Erwin TM, Parada LF (2001) Brain remodeling due to neuronal and astrocytic proliferation after controlled cortical injury in mice. J Neurosci Res 66:317–326PubMedCrossRefGoogle Scholar
  58. 58.
    Fitch MT, Silver J (1997) Glial cell extracellular matrix: boundaries for axon growth in development and regeneration. Cell Tissue Res 290:379–384PubMedCrossRefGoogle Scholar
  59. 59.
    Rock RB, Gekker G, Hu S, Sheng WS, Cheeran M, Lokensgard JR, Peterson PK (2004) Role of microglia in central nervous system infections. Clin Microbiol Rev 17:942–964, table of contentsPubMedCrossRefGoogle Scholar
  60. 60.
    Neumann H, Kotter MR, Franklin RJ (2009) Debris clearance by microglia: an essential link between degeneration and regeneration. Brain 132:288–295PubMedCrossRefGoogle Scholar
  61. 61.
    Polazzi E, Levi G, Minghetti L (1999) Human immunodeficiency virus type 1 Tat protein stimulates inducible nitric oxide synthase expression and nitric oxide production in microglial cultures. J Neuropathol Exp Neurol 58(8):825–831PubMedCrossRefGoogle Scholar
  62. 62.
    Liu B, Jiang JW, Wilson BC, Du L, Yang SN, Wang JY, Wu GC, Cao XD, Hong JS (2000) Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide. J Pharmacol Exp Ther 295(1):125–132PubMedGoogle Scholar
  63. 63.
    Teeling JL, Perry VH (2009) Systemic infection and inflammation in acute CNS injury and chronic neurodegeneration: underlying mechanisms. Neuroscience 158(3):1062–1073PubMedCrossRefGoogle Scholar
  64. 64.
    Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387–1394PubMedCrossRefGoogle Scholar
  65. 65.
    Block ML, Hong JS (2005) Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 76:77–98PubMedCrossRefGoogle Scholar
  66. 66.
    Rohl C, Lucius R, Sievers J (2007) The effect of activated microglia on astrogliosis parameters in astrocyte cultures. Brain Res 1129:43–52PubMedCrossRefGoogle Scholar
  67. 67.
    Cernak I, Stoica B, Byrnes KR, Di Giovanni S, Faden AI (2005) Role of the cell cycle in the pathobiology of central nervous system trauma. Cell Cycle 4:1286–1293PubMedGoogle Scholar
  68. 68.
    Gunther A, Kuppers-Tiedt L, Schneider PM, Kunert I, Berrouschot J, Schneider D, Rossner S (2005) Reduced infarct volume and differential effects on glial cell activation after hyperbaric oxygen treatment in rat permanent focal cerebral ischaemia. Eur J NeuroSci 21:3189–3194PubMedCrossRefGoogle Scholar
  69. 69.
    Miller JM, McAllister JP (2007) Reduction of astrogliosis and microgliosis by cerebrospinal fluid shunting in experimental hydrocephalus. Cerebrospinal Fluid Res 4:5PubMedCrossRefGoogle Scholar
  70. 70.
    Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8:57–69PubMedCrossRefGoogle Scholar
  71. 71.
    Hu X, Zhang D, Pang H, Caudle WM, Li Y, Gao H, Liu Y, Qian L, Wilson B, Di Monte DA, Ali SF, Zhang J, Block ML, Hong JS (2008) Macrophage antigen complex-1 mediates reactive microgliosis and progressive dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. J Immunol 181:7194–7204PubMedGoogle Scholar
  72. 72.
    Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312–318PubMedCrossRefGoogle Scholar
  73. 73.
    Gonzalez-Scarano F, Baltuch G (1999) Microglia as mediators of inflammatory and degenerative diseases. Annu Rev Neurosci 22:219–240PubMedCrossRefGoogle Scholar
  74. 74.
    Nguyen VT, Benveniste EN (2002) Critical role of tumor necrosis factor-alpha and NF-kappa B in interferon-gamma -induced CD40 expression in microglia/macrophages. J Biol Chem 277:13796–13803PubMedCrossRefGoogle Scholar
  75. 75.
    Gehrmann J (1996) Microglia: a sensor to threats in the nervous system? Res Virol 147:79–88PubMedCrossRefGoogle Scholar
  76. 76.
    Zhang D, Hu X, Qian L, Wilson B, Lee C, Flood P, Langenbach R, Hong JS (2009) Prostaglandin E2 released from activated microglia enhances astrocyte proliferation in vitro. Toxicol Appl Pharmacol 238:64–70PubMedCrossRefGoogle Scholar
  77. 77.
    Schmitt AB, Brook GA, Buss A, Nacimiento W, Noth J, Kreutzberg GW (1998) Dynamics of microglial activation in the spinal cord after cerebral infarction are revealed by expression of MHC class II antigen. Neuropathol Appl Neurobiol 24:167–176PubMedCrossRefGoogle Scholar
  78. 78.
    v Eitzen U, Egensperger R, Kösel S, Grasbon-Frodl EM, Imai Y, Bise K, Kohsaka S, Mehraein P, Graeber MB (1998) Microglia and the development of spongiform change in Creutzfeldt-Jakob disease. J Neuropathol Exp Neurol 57(3):246–56CrossRefGoogle Scholar
  79. 79.
    Graeber MB, Kreutzberg GW (1988) Delayed astrocyte reaction following facial nerve axotomy. J Neurocytol 17:209–220PubMedCrossRefGoogle Scholar
  80. 80.
    Gehrmann J, Schoen SW, Kreutzberg GW (1991) Lesion of the rat entorhinal cortex leads to a rapid microglial reaction in the dentate gyrus. A light and electron microscopical study. Acta Neuropathol 82:442–455PubMedCrossRefGoogle Scholar
  81. 81.
    Dusart I, Schwab ME (1994) Secondary cell death and the inflammatory reaction after dorsal hemisection of the rat spinal cord. Eur J NeuroSci 6:712–724PubMedCrossRefGoogle Scholar
  82. 82.
    Frank M, Wolburg H (1996) Cellular reactions at the lesion site after crushing of the rat optic nerve. Glia 16:227–240PubMedCrossRefGoogle Scholar
  83. 83.
    Liberatore GT, Jackson-Lewis V, Vukosavic S, Mandir AS, Vila M, McAuliffe WG, Dawson VL, Dawson TM, Przedborski S (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med 5:1403–1409PubMedCrossRefGoogle Scholar
  84. 84.
    McCann MJ, O’Callaghan JP, Martin PM, Bertram T, Streit WJ (1996) Differential activation of microglia and astrocytes following trimethyl tin-induced neurodegeneration. Neuroscience 72:273–281PubMedCrossRefGoogle Scholar
  85. 85.
    Murphy M, Dutton R, Koblar S, Cheema S, Bartlett P (1997) Cytokines which signal through the LIF receptor and their actions in the nervous system. Prog Neurobiol 52:355–378PubMedCrossRefGoogle Scholar
  86. 86.
    Hanisch UK (2002) Microglia as a source and target of cytokines. Glia 40:140–155PubMedCrossRefGoogle Scholar
  87. 87.
    Beattie MS (2004) Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol Med 10:580–583PubMedCrossRefGoogle Scholar
  88. 88.
    Norris JG, Tang LP, Sparacio SM, Benveniste EN (1994) Signal transduction pathways mediating astrocyte IL-6 induction by IL-1 beta and tumor necrosis factor-alpha. J Immunol 152:841–850PubMedGoogle Scholar
  89. 89.
    Nakamura M, Okada S, Toyama Y, Okano H (2005) Role of IL-6 in spinal cord injury in a mouse model. Clin Rev Allergy Immunol 28:197–204PubMedCrossRefGoogle Scholar
  90. 90.
    Lacy M, Jones J, Whittemore SR, Haviland DL, Wetsel RA, Barnum SR (1995) Expression of the receptors for the C5a anaphylatoxin, interleukin-8 and FMLP by human astrocytes and microglia. J Neuroimmunol 61:71–78PubMedCrossRefGoogle Scholar
  91. 91.
    Dorf ME, Berman MA, Tanabe S, Heesen M, Luo Y (2000) Astrocytes express functional chemokine receptors. J Neuroimmunol 111:109–121PubMedCrossRefGoogle Scholar
  92. 92.
    Sawada M, Itoh Y, Suzumura A, Marunouchi T (1993) Expression of cytokine receptors in cultured neuronal and glial cells. Neurosci Lett 160:131–134PubMedCrossRefGoogle Scholar
  93. 93.
    Benveniste EN, Benos DJ (1995) TNF-alpha- and IFN-gamma-mediated signal transduction pathways: effects on glial cell gene expression and function. Faseb J 9:1577–1584PubMedGoogle Scholar
  94. 94.
    Pickering M, Cumiskey D, O’Connor JJ (2005) Actions of TNF-alpha on glutamatergic synaptic transmission in the central nervous system. Exp Physiol 90:663–670PubMedCrossRefGoogle Scholar
  95. 95.
    Barna BP, Estes ML, Jacobs BS, Hudson S, Ransohoff RM (1990) Human astrocytes proliferate in response to tumor necrosis factor alpha. J Neuroimmunol 30:239–243PubMedCrossRefGoogle Scholar
  96. 96.
    Cardenas H, Bolin LM (2003) Compromised reactive microgliosis in MPTP-lesioned IL-6 KO mice. Brain Res 985:89–97PubMedCrossRefGoogle Scholar
  97. 97.
    Herx LM, Yong VW (2001) Interleukin-1 beta is required for the early evolution of reactive astrogliosis following CNS lesion. J Neuropathol Exp Neurol 60:961–971PubMedGoogle Scholar
  98. 98.
    Mohri I, Taniike M, Taniguchi H, Kanekiyo T, Aritake K, Inui T, Fukumoto N, Eguchi N, Kushi A, Sasai H, Kanaoka Y, Ozono K, Narumiya S, Suzuki K, Urade Y (2006) Prostaglandin D2-mediated microglia/astrocyte interaction enhances astrogliosis and demyelination in twitcher. J Neurosci 26:4383–4393PubMedCrossRefGoogle Scholar
  99. 99.
    Selmaj KW, Farooq M, Norton WT, Raine CS, Brosnan CF (1990) Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor. J Immunol 144:129–135PubMedGoogle Scholar
  100. 100.
    Balasingam V, Tejada-Berges T, Wright E, Bouckova R, Yong VW (1994) Reactive astrogliosis in the neonatal mouse brain and its modulation by cytokines. J Neurosci 14:846–856PubMedGoogle Scholar
  101. 101.
    Giulian D, Woodward J, Young DG, Krebs JF, Lachman LB (1988) Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization. J Neurosci 8:2485–2490PubMedGoogle Scholar
  102. 102.
    Herx LM, Rivest S, Yong VW (2000) Central nervous system-initiated inflammation and neurotrophism in trauma: IL-1 beta is required for the production of ciliary neurotrophic factor. J Immunol 165:2232–2239PubMedGoogle Scholar
  103. 103.
    Sriram K, Miller DB, O’Callaghan JP (2006) Minocycline attenuates microglial activation but fails to mitigate striatal dopaminergic neurotoxicity: role of tumor necrosis factor-alpha. J Neurochem 96:706–718PubMedCrossRefGoogle Scholar
  104. 104.
    von Boyen GB, Steinkamp M, Reinshagen M, Schafer KH, Adler G, Kirsch J (2004) Proinflammatory cytokines increase glial fibrillary acidic protein expression in enteric glia. Gut 53:222–228CrossRefGoogle Scholar
  105. 105.
    Lotan M, Schwartz M (1994) Cross talk between the immune system and the nervous system in response to injury: implications for regeneration. Faseb J 8:1026–1033PubMedGoogle Scholar
  106. 106.
    Raghavendra V, Tanga F, DeLeo JA (2003) Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J Pharmacol Exp Ther 306:624–630PubMedCrossRefGoogle Scholar
  107. 107.
    Leonardo CC, Eakin AK, Ajmo JM, Collier LA, Pennypacker KR, Strongin AY, Gottschall PE (2008) Delayed administration of a matrix metalloproteinase inhibitor limits progressive brain injury after hypoxia-ischemia in the neonatal rat. J Neuroinflammation 5:34PubMedCrossRefGoogle Scholar
  108. 108.
    Raivich G, Moreno-Flores MT, Moller JC, Kreutzberg GW (1994) Inhibition of posttraumatic microglial proliferation in a genetic model of macrophage colony-stimulating factor deficiency in the mouse. Eur J NeuroSci 6:1615–1618PubMedCrossRefGoogle Scholar
  109. 109.
    Tian DS, Dong Q, Pan DJ, He Y, Yu ZY, Xie MJ, Wang W (2007) Attenuation of astrogliosis by suppressing of microglial proliferation with the cell cycle inhibitor olomoucine in rat spinal cord injury model. Brain Res 1154:206–214PubMedCrossRefGoogle Scholar
  110. 110.
    Spataro L, Dilgen J, Retterer S, Spence AJ, Isaacson M, Turner JN, Shain W (2005) Dexamethasone treatment reduces astroglia responses to inserted neuroprosthetic devices in rat neocortex. Exp Neurol 194:289–300PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Dan Zhang
    • 1
  • Xiaoming Hu
    • 1
    • 2
  • Li Qian
    • 1
    • 3
  • James P. O’Callaghan
    • 4
  • Jau-Shyong Hong
    • 1
  1. 1.Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health SciencesNational Institutes of HealthResearch Triangle ParkUSA
  2. 2.Department of Neurology and Pittsburgh Institute of Neurodegenerative DiseasesUniversity of Pittsburgh School of MedicinePittsburghUSA
  3. 3.Comprehensive Center for Inflammatory DisordersUniversity of North CarolinaChapel HillUSA
  4. 4.Centers for Disease Control and PreventionNational Institute for Occupational Safety and HealthMorgantownUSA

Personalised recommendations