Neurochemical Research

, Volume 17, Issue 9, pp 877–885

Quantitative aspects of reactive gliosis: A review

  • W. T. Norton
  • D. A. Aquino
  • I. Hozumi
  • F. -C. Chiu
  • C. F. Brosnan
Original Articles

Abstract

Recent studies of gliosis in a variety of animal models are reviewed. The models include brain injury, neurotoxic damage, genetic diseases and inflammatory demyelination. These studies show that reactive gliosis is not a stereotypic response, but varies widely in duration, degree of hyperplasia, and time course of expression of GFAP immunostaining, content and mRNA. We conclude that there are different biological mechanisms for induction and maintenance of reactive gliosis, which, depending on the kind of tissue damage, result in different expressions of the gliotic response.

Key Words

Gliosis astrocytes GFAP brain damage demyelination 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Nathaniel, E. J. H., and Nathaniel, D. R. 1981. The reactive astrocyte. Pages 249–301,in Fedoroff, S., and Hertz, L. (eds.), Advances in Cellular Neurobiology, Vol. 2, Academic Press, New York.Google Scholar
  2. 2.
    Lindsay, R. M. 1986. Reactive gliosis. Pages 231–262,in S. Fedoroff and A. Vernadakis (eds.) Astrocytes, Vol. 3, Academic Press, New York.Google Scholar
  3. 3.
    Hatten, M. E., Liem, R. K. H., Shelanski, M. L., and Mason, C. A. 1991. Astroglia in CNS injury. Glia 4:233–243.Google Scholar
  4. 4.
    Eng, L. F., Vanderhaegen, J. J., Bignami, A., and Gerstl, B. 1971. An acidic protein isolated from fibrous astrocytes. Brain Res. 28:351–354.Google Scholar
  5. 5.
    Bignami, A., Eng, L. F., Dahl, D., and Uyeda, C. T. 1972. Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence. Brain Res. 43:429–435.Google Scholar
  6. 6.
    Eng, L. F. 1985. Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. J. Neuroimmunol. 8:203–214.Google Scholar
  7. 7.
    Cavanagh, J. B. 1970. The proliferation of astrocytes around a needle wound in the rat brain. J. Anat. 106:471–487.Google Scholar
  8. 8.
    Bignami, A., and Dahl, D. 1976. The astroglial response to stabbing. Immunofluorescence studies with antibodies to astrocyte-specific protein (GFA) in mammalian and submammalian vertebrates. Neuropathol. Appl. Neurobiol. 2:99–111.Google Scholar
  9. 9.
    Latov, N., Nilaver, G., Zimmerman, E. A., Johnson, W. G., Silverman, A.-J., Defendini, R., and Cote, L. 1979. Fibrillary astrocytes proliferate in response to brain injury. Dev. Biol. 72:381–384.Google Scholar
  10. 10.
    Pixley, S. R., and deVellis, J. 1984. Transition between immature radial glia and mature astrocytes studied with a monoclonal antibody to vimentin. Dev. Brain Res. 15:201–209.Google Scholar
  11. 11.
    Mathewson, A. J., and Berry, M. 1985. Observations on the astrocyte response to a cerebral stab wound in adult rats. Brain Res. 327:61–69.Google Scholar
  12. 12.
    Ludwin, S. K. 1985. Reaction of oligodendrocytes and astrocytes to trauma and implantation. Lab. Invest. 52:20–30.Google Scholar
  13. 13.
    Miyake, T., Hattori, T., Fukuda, M., Kitamura, T., and Fujita, S. 1988. Quantitative studies on proliferative changes of reactive astrocytes in mouse cerebral cortex. Brain Res. 451:133–138.Google Scholar
  14. 14.
    Miyake, T., Hattori, T., Fukuda, M., and Kitamura, T. 1989. Reactions of S-100-positive glia after injury of mouse cerebral cortex. Brain Res. 489:31–40.Google Scholar
  15. 15.
    Takamiya, Y., Kohsaka, S., Otani, M., and Tsukada, Y. 1988. Immunohistochemical studies on the proliferation of reactive astrocytes and the expression of cytoskeletal proteins following brain injury in rats. Develop. Brain Res. 38:201–210.Google Scholar
  16. 16.
    Janeczko, K. 1988. The proliferative response of astrocytes to injury in neonatal rat brain. A combined immunocytochemical and autoradiographic study. Brain Red. 456:280–285.Google Scholar
  17. 17.
    Topp, K. S., Faddis, B. T., and Vijayan, V. K. 1989. Trauma-induced proliferation of astrocytes in the brains of young and aged rats. Glia 2:201–211.Google Scholar
  18. 18.
    Hozumi, I., Chiu, F.-C., and Norton, W. T. 1990. Biochemical and immunocytochemical changes in glial fibrillary acidic protein after stab wounds. Brain Res. 524:64–71.Google Scholar
  19. 19.
    Hozumi, I., Aquino, D. A., and Norton, W. T. 1990. GFAP mRNA levels following stab wounds in rat brain. Brain Res. 534:291–294.Google Scholar
  20. 20.
    Condorelli, D. F., Dell'Albani, P., Kaczmarek, L., Messina, L., Spampinato, G., Avola, R., Messina, A., and Guiffrida Stella, A. M. 1990. Glial fibrillary acidic protein messenger RNA and glutamine synthetase activity after nervous system injury. J. Neurosci. Res. 26:251–257.Google Scholar
  21. 21.
    Amaducci, L., Forno, K. I., and Eng, L. F. 1981. Glial fibrillary acidic protein in cryogenic lesions of the rat brain. Neurosci. Lett. 21:27–32.Google Scholar
  22. 22.
    Schiffer, D., Giordana, M. T., Migheli, A., Giaccone, G., Pezzotta, S., and Mauro, A. 1986. Glial fibrillary acidic protein and vimentin in the experimental glial reaction of the rat brain. Brain Res. 374:110–118.Google Scholar
  23. 23.
    Moumdjian, R. A., Antel, J. P., and Yong, V. W. 1991. Origin of contralateral reactive gliosis in surgically injured rat cerebral cortex. Brain Res. 547:223–228.Google Scholar
  24. 24.
    Shehab, S. A. S., Cronly-Dillon, J. R., Nona, S. N., and Stafford, C. A. 1990. Preferential histochemical staining of protoplasmic and fibrous astrocytes in rat CNS with GFAP antibodies using different fixatives. Brain Res. 518:347–352.Google Scholar
  25. 25.
    Morshead, C. M., and van der Kooy, D. 1990. Separate blood and brain origins of proliferating cells during gliosis in adult brains. Brain Res. 535:237–244.Google Scholar
  26. 26.
    Katz, I. R., Iacovitti, L. M., and Reis, D. J. 1990. In vitro studies on the characterization of cellular proliferation following normal injury in the adult rat brain. J. Neuroimmunol. 29:33–48.Google Scholar
  27. 27.
    Dahl, D., Bignami, A., Weber, K., and Osborn, M. 1981. Filament proteins in rat optic nerves undergoing Wallerian degeneration: localization of vimentin, the fibroblastic 100-A filament protein in normal and reactive astrocytes. Exp. Neurol. 73:496–506.Google Scholar
  28. 28.
    Petito, C. K., Morgello, S., Felix, J. C., and Lesser, M. L. 1990. The two patterns of reactive astrocytosis in postischemic rat brain. J. Cereb. Blood Flow Metab. 10:850–850.Google Scholar
  29. 29.
    Dahl, D. 1981. The vimentin-GFA protein transition in rat neuroglia cytoskeleton occurs at the time of myelination. J. Neurosci. Res. 6:744–748.Google Scholar
  30. 30.
    Schnitzer, J., Franke, W. W., and Schachner, M. 1981. Immunohistochemical demonstration of vimentin in astrocytes and ependymal cells of developing and adult nervous system. J. Cell Biol. 90:435–437.Google Scholar
  31. 31.
    Yen, S.-H., and Fields, K. L. 1981. Antibodies to neurofilament glial filament and fibroblast intermediate filament proteins bind to different cell types of the nervous system. J. Cell Biol. 88:115–126.Google Scholar
  32. 32.
    Bovolenta, P., Liem, R. H. K., and Mason, C. A. 1984. Development of cerebellar astroglia-transition in form and cytoskeletal content. Develop. Biol. 102:248–259.Google Scholar
  33. 33.
    Geisert, E. E., Jr., Johnson, H. G., and Binder, L. I. 1990. Expression of microtubule-associated protein 2 by reactive astrocytes. Proc. Natl. Acad. Sci. USA 87:3967–3971.Google Scholar
  34. 34.
    Brock, T. O., and O'Callaghan, J. P. 1987. Quantitative changes in the synaptic vesicle proteins synapsin I and p38 and the astrocyte-specific glial fibrillary acidic protein are associated with chemical-induced injury to the rat central nervous system. J. Neurosci. 7:931–942.Google Scholar
  35. 35.
    O'Callaghan, J. P., Miller, D. B., and Reinhard, J. F., Jr. 1990. Characterization of the origins of the astrocyte response to injury using the dopaminergic neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Brain Res. 521:73–80.Google Scholar
  36. 36.
    Rataboul, P., Vernier, P., Faucon Biguet, N., Mallet, J., Poulat, P., and Privat, A. 1989. Modulation of GFAP mRNA levels following toxic lesions in the basal ganglia of the rat. Brain Res. Bull. 22:155–161.Google Scholar
  37. 37.
    Schaumburg, H. H., Powers, J. M., Raine, C. S., Suzuki, K., and Richardson, E. P. 1975. Adrenoleukodystrophy. A clinical and pathological study of 17 cases. Arch. Neurol. 33:577–591.Google Scholar
  38. 38.
    Goldman, J. E., Schaumburg, H. H., and Norton, W. T. 1978. Isolation and characterization of glial filaments from human brain. J. Cell Biol. 78:426–440.Google Scholar
  39. 39.
    Baumann, N., Jacque, C., and Dupouey, P. 1986. Astrocyte modifications in neurological mutations of the mouse. Pages 325–336,in Fedoroff, S., and Vernadakis, A. (eds.), Astrocytes, Vol. 2, Academic Press, Orlando.Google Scholar
  40. 40.
    Seyfried, T. N., and Yu, R. K. 1985. Ganglioside GD3: structure, cellular distribution and possible function. Mol. Cell Biochem. 68:3–10.Google Scholar
  41. 41.
    Levine, S. M., Seyfried, T. N., Yu, R. K., and Goldman, J. E. 1986. Immunocytochemical localization of GD3 ganglioside to astrocytes in murine cerebellar mutants. Brain Res. 374:260–269.Google Scholar
  42. 42.
    Goldman, J. E., Hirano, M., Yu, R. K., and Seyfried, T. N. 1984. GD3 ganglioside is a glycolipid characteristic of immature neuroectodermal cells. J. Neuroimmunol. 7:179–192.Google Scholar
  43. 43.
    Goldman, J. E., Geier, S. S., and Hirano, M. 1986. Differentiation of astrocytes and oligodendrocytes from germinal matrix cells in primary culture. J. Neurosci. 6:52–60.Google Scholar
  44. 44.
    Yu, R.K., Ledeen, R. W., and Eng, L. F. 1974. Ganglioside abnormalities in multiple sclerosis. J. Neurochem. 23:169–174.Google Scholar
  45. 45.
    O'Callaghan, J. P., and Miller, D. B. 1985. Cerebellar hypoplasia in the Gunn rat is associated with quantitative changes in neurotypic and gliotypic proteins. J. Pharmacol. Exp. Ther. 234:522–533.Google Scholar
  46. 46.
    Kobayashi, S., Chiu, F.-C., Katayama, M., Sacchi, R. S., Suzuki, K., and Suzuki, K. 1986. Expression of glial fibrillary acidic protein in the CNS and PNS of murine globoid cell leukodystrophy, the twitcher. Am. J. Pathol. 125:227–243.Google Scholar
  47. 47.
    Chiu, F.-C., Sacchi, R. S., Claudio, L., Kobayashi, S., and Suzuki, K. 1988. Coexpression of glial fibrillary acidic protein and vimentin in the central and peripheral nervous systems of the twitcher mutant. Glia 1:105–112.Google Scholar
  48. 48.
    Shafit-Zagardo, B., Peterson, C., and Goldman, J. E. 1988. Rapid increases in glial fibrillary acidic protein mRNA and protein levels in the copper-deficient brindled mouse. J. Neurochem. 51:1258–1266.Google Scholar
  49. 49.
    Igisu, H., and Suzuki, K. 1984. Progressive accumulation of toxic metabolite in a genetic leukodystrophy. Science 224:753–755.Google Scholar
  50. 50.
    Raine, C. S. 1983. Multiple sclerosis and chronic relapsing EAE — Comparative ultrastructure and neuropathology. Pages 413–460,in Hallpike, J. F., Adams, C. W. M., and Tourtellotte, W. W. (eds.), Multiple Sclerosis — Pathology, Diagnosis and Management, Williams and Wilkins, Baltimore, MD.Google Scholar
  51. 51.
    Linington, C., Suckling, A. J., Weir, M. D., and Cuzner, M. L. 1984. Changes in the metabolism of glial fibrillary acidic protein (GFAP) during chronic relapsing experimental allergic encephalomyelitis in the strain 13 guinea pig. Neurochem. Int. 6:393–401.Google Scholar
  52. 52.
    Smith, M. E., and Eng, L. F. 1987. Glial fibrillary acidic protein in chronic relapsing experimental allergic encephalomyelitis in SJL/J mice. J. Neurosci. Res. 18:203–208.Google Scholar
  53. 53.
    Smith, M. E., Somera, F. P., and Eng, L. F. 1983. Immunocytochemical staining for glial fibrillary acidic protein and the metabolism of cytoskeletal proteins in experimental allergic encephalomyelitis. Brain Res. 264:241–253.Google Scholar
  54. 54.
    Smith, M. E., Gibbs, M. A., Forno, L. S., and Eng, L. F. 1987. [3H]Thymidine labeling of astrocytes in experimental allergic encephalomyelitis. J. Neuroimmunol. 15:309–321.Google Scholar
  55. 55.
    Goldmuntz, E. A., Brosnan, C. F., Chiu, F.-C., and Norton, W. T. 1986. Astrocytic reactivity and intermediate filament metabolism in experimental autoimmune encephalomyelitis: the effect of suppression with prazosin. Brain Res. 397:16–26.Google Scholar
  56. 56.
    Aquino, D. A., Chiu, F.-C., Brosnan, C. F., and Norton, W. T. 1988. Glial fibrillary acidic protein increases in the spinal cord of Lewis rats with acute experimental autoimmune encephalomyelitis. J. Neurochem. 51:1085–1096.Google Scholar
  57. 57.
    Aquino, D. A., Shafit-Zagardo, B., Brosnan, C. F., and Norton, W. T. 1990. Expression of glial fibrillary acidic protein and neurofilament mRNA in gliosis induced by experimental autoimmune encephalomyelitis. J. Neurochem. 54:1398–1404.Google Scholar
  58. 58.
    Brosnan, C. F., Goldmuntz, E. A., Cammer, W., Factor, S. M., Bloom, B. R., and Norton, W. T. 1985. Prazosin, an 884-1 receptor antagonist, suppresses experimental autoimmune encephalomyelitis in the Lewis rat. Proc. Natl. Acad. Sci. U.S.A. 82:5915–5919.Google Scholar
  59. 59.
    Goldmuntz, E. A., Brosnan, C. F., and Norton, W. T. 1986. Prazosin treatment suppresses increased vascular permeability in both acute and passively transferred experimental autoimmune encephalomyelitis in the Lewis rat. J. Immunol. 137:3444–3450.Google Scholar
  60. 60.
    Eng, L. F., D'Amelio, F. E., and Smith, M. E. 1989. Dissociation of GFAP intermediate filaments in EAE: Observations in the lumbar spinal cord. Glia 2:308–317.Google Scholar
  61. 61.
    Cammer, W., Tansey, F. A., and Brosnan, C. F. 1989. Gliosis in the spinal cords of rats with experimental allergic encephalomyelitis: Immunostaining of carbonic anhydrase and vimentin in reactive astrocytes. Glia 2:223–230.Google Scholar
  62. 62.
    Cammer, W., Tansey, F. A., and Brosnan, C. F. 1990. Reactive gliosis in the brains of Lewis rats with experimental allergic encephalomyelitis. J. Neuroimmunol. 27:111–120.Google Scholar
  63. 63.
    Oldendorf, W. H., and Towner, H. F. 1974. Blood-brain barrier and DNA changes during the evolution of experimental allergic encephalomyelitis. J. Neuropathol. Exp. Neurol. 33:616–631.Google Scholar
  64. 64.
    Smith, M. E., Somera, F. P., Saldivar, R., Massacesi, L., and Trotter, J. 1984. DNA changes in spinal cords of rats with experimental allergic encephalomyelitis. J. Neurochem. 43:1635–1641.Google Scholar
  65. 65.
    Aquino, D. A., Brosnan, C. F., and Norton, W. T. 1990. Stress proteins in acute EAE spinal cord. Trans. Am. Soc. Neurochem. 21:258.Google Scholar
  66. 66.
    Aquino, D. A., Brosnan, C. F. and Norton, W. T. 1991. Stress proteins and c-fos in acute EAE spinal cord. J. Neurochem. 57(Suppl.), 570B.Google Scholar
  67. 67.
    Brown, I. R., Rush, S., and Ivy, G. O. 1989. Induction of a heat shock gene at the site of tissue injury in the rat brain. Neuron 2:1559–1564.Google Scholar
  68. 68.
    Dragunow, M., and Robertson, H. A. 1988. Brain injury induces c-fos protein(s) in nerve and glial-like cells in adult mammalian brain. Brain Res. 455:295–299.Google Scholar
  69. 69.
    Guilian, D., Chen, J., Ingeman, J. E., George, J. K., and Noponen, M. 1989. The role of mononuclear phagocytes in wound healing after traumatic injury to mammalian brain. J. Neurosci. 9:4416–4429.Google Scholar
  70. 70.
    Guilian, D., and Lachman, L. B. 1985. Interleukin-1 stimulation of astroglial proliferation after brain injury. Science 228:497–499.Google Scholar
  71. 71.
    Guilian, D., Woodward, J., Young, D. G., Krebs, J. F., and Lachman, L. B. 1988. Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization. J. Neurosci. 8:2485–2490.Google Scholar
  72. 72.
    Selmaj, K. W., Farooq, M., Norton, W. T., Raine, C. S., and Brosnan, C. F. 1990. Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor. J. Immunol. 144:129–135.Google Scholar
  73. 73.
    Barna, B. P., Estes, M. L., Jacobs, B. S., Hudson, S., and Ransohoff, R. M. 1990. Human astrocytes proliferate in response to tumer necrosis factor alpha. J. Neuroimmunol., 30:239–243.Google Scholar
  74. 74.
    Selmaj, K., Shafit-Zagardo, B., Aquino, D. A., Farooq, M., Raine, C. S., Norton, W. T., and Brosnan, C. F. 1991. Tumor necrosis factor-induced proliferation of astrocytes from mature brain is associated with down-regulation of glial fibrillary acidic protein mRNA. J. Neurochem. 57:823–830.Google Scholar
  75. 75.
    Chiu, F.-C., and Goldman, J. E. 1985. Regulation of glial fibrillary acidic protein (GFAP) expression in CNS development and in pathological states. J. Neuroimmunol. 8:283–292.Google Scholar
  76. 76.
    Shafit-Zagardo, B., Kume-Iwaki, A., and Goldman, J. E. 1988. Astrocytes regulate GFAP mRNA levels by cyclic AMP and protein kinase C-dependent mechanisms. Glia 1:346–354.Google Scholar
  77. 77.
    Morrison, R. S., De Vellis, J., Lee, Y. L., Bradshaw, R. A., and Eng, L. F. 1985. Hormones and growth factors induce the synthesis of glial fibrillary acidic protein in rat brain astrocytes. J. Neurosci. Res. 14:167–176.Google Scholar
  78. 78.
    O'Callaghan, J. P., Brinton, R. E., and McEwen, B. S. 1989. Glucocorticoids regulate the concentration of glial fibrillary acidic protein throughout the brain. Brain Res. 494:159–161.Google Scholar
  79. 79.
    Nichols, N. R., Osterburg, H. H., Masters, J. N., Millar, S. L., and Finch, C. E. 1990. Messenger RNA for glial fibrillary acidic protein is decreased in rat brain following acute and chronic corticosterone treatment. Mol. Brain Res. 7:1–7.Google Scholar

Copyright information

© Plenum Publishing Corporation 1992

Authors and Affiliations

  • W. T. Norton
    • 1
    • 2
  • D. A. Aquino
    • 1
  • I. Hozumi
    • 1
  • F. -C. Chiu
    • 1
    • 2
  • C. F. Brosnan
    • 2
    • 3
  1. 1.Department of NeurologyAlbert Einstein College of MedicineBronx
  2. 2.Department of NeuroscienceAlbert Einstein College of MedicineBronx
  3. 3.Department of PathologyAlbert Einstein College of MedicineBronx
  4. 4.Department of Neurology, Brain Research InstituteNiigata UniversityNiigataJapan

Personalised recommendations