Reactive Astrogliosis in the Injured and Postischemic Brain

  • Ronald Jabs
  • Lane K. Bekar
  • Wolfgang Walz
Part of the Contemporary Neuroscience book series (CNEURO)


Reactive astrocytes appear within days of a disturbance or injury to the brain. They form part of a gliotic or scar tissue, which can take on a very complex form, depending on the type and intensity of the disturbance. Reactive astrocytes are usually characterized by morphological changes and increases in intermediate filaments. However, other more functional characteristics are not as well-characterized. In particular, glial interactions with surviving neurones are not very well-defined. Some attention has been paid to glial upregulation of protective factors and changes in expression of extracellular matrix, but changes in membrane properties and homeostatic mechanisms have received very little regard. This is true for injury in general, but is especially true following ischemic injury.


Nerve Growth Factor Glutamine Synthetase Reactive Astrocyte Neural Cell Adhesion Molecule Kainic Acid 
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.


  1. Akopian, G., Kuprijanova, E., Kressin, K., and Steinhauser, C. (1997) Analysis of ion channel expression by astrocytes in red nucleus brain stem slices of the rat. Glia 19, 234–246.PubMedCrossRefGoogle Scholar
  2. Altman, J., and Das, G. D. (1964) Autoradiographic examination of the effects of enriched environment on the rate of glial multiplication in the adult rat brain. Nature 204, 1161–1163.PubMedCrossRefGoogle Scholar
  3. Balasingham, V., Tejada Berges, T., Wright, E., Bouckova, R., and Yong, V. W. (1994) Reactive astrogliosis in the neonatal mouse brain and its modulation by cytokines. J. Neurosci 14, 846–856.Google Scholar
  4. Bovolenta, P Wandosell, F., and Nicto-Sampedro, N. (1993) Neurite outgrowth inhibitors associated with glial cells and glial cell lines. Neuroreport 5 345–348.Google Scholar
  5. Carson, M. J, Thomas, E. A., Danielson, P. E., and Sutcliffe, J. G. (1996) The 5-HT5A serotonin receptor is expressed predominantly by astrocytes in which it inhibits cAMP accumulation. Glia 17, 317–326.Google Scholar
  6. Chvatal, A., Pastor, A., Mauch, M., Sykova, E., and Kettenmann, H. (1995) Distinct populations of identified glial cells in the developing rat spinal cord slice. Eur. J. Neurosci 7, 129–142.PubMedCrossRefGoogle Scholar
  7. Courville, C. B. (1964) Forensic Neuropathology, Callaghan, Mundelein, IL.Google Scholar
  8. Crutcher, K. A., Brothers, L., and Davis, J. N. (1979) Sprouting of sympathetic nerves in the absence of afferent input. Exp. Neurol 66, 778–783.Google Scholar
  9. da Cunha, A., Jefferson, J. J., Tyor, W. R., Glass, J. D., Jannotta, F. S., and Vitkovic, L. (1993) Gliosis in human brain: relationship to size but not other properties of astrocytes. Brain Res. 600, 161–165.Google Scholar
  10. David, S., and Ness, R. (1993) Heterogeneity of reactive astrocytes, in Biology and Pathology of Astrocyte-Neuron Interactions. (Fedoroff S., Juurlink B. H., and Doucette R., eds.), Plenum, New York, pp. 303–312.Google Scholar
  11. Diamond, M. C., Law, F., Rhodes, H., Lindner, B., Rosenzweig, M. R., Krech, D., and Bennett, E. L. (1966) Increases in cortical depth and glia numbers in rats subjected to enriched environment. J. Comp. Neurol 128, 117–126.Google Scholar
  12. Eddleston, M. and Mucke, L. (1993) Molecular profile of reactive astrocytes. Neuroscience 54, 15–36.PubMedCrossRefGoogle Scholar
  13. Faissner, A., and Schachner, M. (1995) Tenascin and janusin, in Neuroglia (Kettenmann H., and Ransom B., eds,), Oxford University Press, New York, pp. 411–426.Google Scholar
  14. Fan, L., Young, P. R., Barone, F. C., Feuerstein, G. Z., Smith, D. H., and McIntosh, T. K. (1995) Experimental brain injury induces expression of interleukin-1 beta mRNA in the rat brain. Mol. Brain Res 30, 125–130.PubMedCrossRefGoogle Scholar
  15. Gary, K. A., and Chronwall, B. M. (1995) Regulation of GFAP expression in glial-like cells of the rat pituitary intermediate lobe by lactation, salt-loading and adrenalectomy. Glia13, 272–282.PubMedCrossRefGoogle Scholar
  16. Gehrmann, J., Mies, G., Bonnekoh, P., Banati, R., Iljima, T., and Kreutzberg (1993) Microglial reaction in the rat cerebral cortex induced by cortical spreading depression. Brain Pathol. 3, 11–17.PubMedCrossRefGoogle Scholar
  17. Gilmore, S. A., and Sims, T. J. (1975) Glial cells and regeneration in the peripheral nervous system, in Neuroglia (Kettenmann H., and Ransom B., eds.), Oxford University Press, New York, pp. 829–842.Google Scholar
  18. Harold, D. E., and Walz, W. (1992) Metabolic inhibition and electrical properties of type1-like cortical astrocytes. Neuroscience 47, 203–211.PubMedCrossRefGoogle Scholar
  19. Hatten, M. E., Liem, R. K. H., Shelanski, M. L., and Mason, C. A. (1991) Astroglia in CNS injury. Glia 4, 233–242.PubMedCrossRefGoogle Scholar
  20. Hossain, M. Z., Peeling, J., Sutherland, G. R., Hertzberg, E. L., and Nagy, J. I. (1994a) Ischemia-induced cellular redistribution of astrocyte gap junctional protein connexin 43 in rat brain. Brain Res. 652, 311–322.PubMedCrossRefGoogle Scholar
  21. Hossain, M. Z., Sawchuk, M. A., Murphy, L. J., Hertzberg, E. L., and Nagy, J. I. (1994b) Kainic acid induced alternations in antibody recognition of connexin43 and loss of astrocytic gap junctions in rat brain. Glia 10, 250–265.PubMedCrossRefGoogle Scholar
  22. Humpel, C., Hoffer, B., Stromberg, I., Bektesh, S., Collins, F., and Olson, L. (1994) Neurons of hippocampal formation express glial cell like-derived neurotrophic factor messenger RNA in response to kainate-induced excitation. Neuroscience 59, 791–795.PubMedCrossRefGoogle Scholar
  23. Inuzuka, T., Hozumi, I., Tamura, X., Hiraiwa, M., and Tsuji, S. (1996) Patterns of growth inhibitory factor and GFAP relative level changes differ following left middle cerebral artery occlusion in rats. Brain Res. 709, 151–153.PubMedCrossRefGoogle Scholar
  24. Jabs, R., Paterson, I. A., and Walz, W. (1997) Qualitative analysis of membrane currents in glial cells from normal and gliotic tissue in situ. Neuroscience 81, 847–860.PubMedCrossRefGoogle Scholar
  25. Janeczko, K. (1993) Co-expression of GFAP and vimentin in astrocytes proliferating in response to injury in the mouse cerebral hemisphere. Int. J. Dev. Neurosci 11, 139–147.PubMedCrossRefGoogle Scholar
  26. Kahn, M. A., Ellison, J. A., Speight, G. J., and De Vellis, J. (1995) CNTF regulation of astrogliosis and the activation of microglia in the developing rat CNS. Brain Res. 685, 55–67.PubMedCrossRefGoogle Scholar
  27. Kraig, R. P., Dong, L., Thisted, R., and Jaeger, C. B. (1991) Spreading depression increases immunohistochemical staining of GFAP. J. Neurosci 11, 2187–2198.PubMedGoogle Scholar
  28. Korr, H. (1980) Proliferation of different cell types in the brain. Adv. Anat. Embryol. Cell. Biol 61, 1–72.PubMedCrossRefGoogle Scholar
  29. Korr, H. (1986) Proliferation and cell cycle parameters of astrocytes, in Astrocytes, vol. 3. (Fedoroff S., and Vernadakis A., eds.), Academic, Orlando, pp. 77–127.Google Scholar
  30. Korr, H., Schilling, W. D., Schultze, B., and Maurer, W. (1983) Autoradiographic studies of glial proliferation in different areas of the brain of the 14-day-old rat. Cell Tissue Kinet. 16, 393–413.PubMedGoogle Scholar
  31. Lehrmann, E., Kiefer, R., Finsen, B., Diemer, N. H., Zimmer, J., and Hartung, H. P. (1995) Cytokines in cerebral ischemia. Exp. Neurol 131, 114–123.Google Scholar
  32. Lindholm, D., Castren, E., Kiefer, R., Zafra, F., and Thoenen, H. (1992) Transforming growth factor-beta 1 in the rat brain. J. Cell. Biol 117, 395–400.PubMedCrossRefGoogle Scholar
  33. Malhotra, S. K., Shnitka, T. K. and Elbrink, J. (1990) Reactive astrocytes. Cytobios 61, 133–160.PubMedGoogle Scholar
  34. McKeon, R. J. and Sliver, J. (1995) Functional significance of glial-derived matrix during development and regeneration, in Neuroglia (Kettenmann H., and Ransom B., eds.), Oxford University Press, New York, pp. 389–410.Google Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. Miyake, T., Okada, M., and Kitamura, T. (1992) Reactive proliferation of astrocytes studied by immunohistochemistry for proliferating cell nuclear antigen. Brain Res. 590, 300–302.PubMedCrossRefGoogle Scholar
  38. Nedergaard, M. and Hansen, A. J. (1988) Spreading depression is not associated with neuronal injury in the normal brain. Brain Res. 449, 395–398.PubMedCrossRefGoogle Scholar
  39. Paterson, J. A. and Leblond, C. P. (1977) Increased proliferation of neuroglia and endothelial cells in the supraoptic nucleus and hypophysial neural lobe of young rats drinking hypertonic sodium chloride solution. J. Comp. Neurol 175, 373–390.PubMedCrossRefGoogle Scholar
  40. Penfield, W. (1932) Cytology and Cellular Pathology of the Nervous System. Paul B. Hoeber, New York, 1267 pp.Google Scholar
  41. Petito, C. K. (1986) Transformation of postischemic perineural glial cells. J. Cereb. Blood Flow Metab 6, 616–624.PubMedCrossRefGoogle Scholar
  42. Petito, C. K., Chung, M. C., Verkhovsky, L. M., and Cooper, A. J. L. (1992) Brain glutamine synthetase increase following cerebral ischemia in the rat. Brain Res. 569, 275–280.PubMedCrossRefGoogle Scholar
  43. Petito, C. K. and Halaby, I. A. (1993) Relationship between ischemia and ischemic neuronal necrosis to astrocyte expression of GFAP. Int. J. Dev. Neurosci 11, 239–247.PubMedCrossRefGoogle Scholar
  44. Petito, C. K., Morgello, S., Felix, J. C., and Lesser, M. L. (1990) Two patterns of reactive astrocytosis in postischemic rat brain. J. Cereb. Blood Flow Metab 10, 850–859.PubMedCrossRefGoogle Scholar
  45. Riva, M. A., Donati, E., Tascedola, F., Zolli, M., and Racagni, G. (1994) Short- and longterm induction of bFGF gene expression in rat CNS following kainate injection. Neuroscience 59, 55–65.PubMedCrossRefGoogle Scholar
  46. Rudge, J. S. (1993) Astrocyte-derived neurotrophic factors, in Astrocytes (Murphy, S., ed.), Academic, San Diego, pp. 267–307.Google Scholar
  47. Saad, B Constam, D. B Ortmann, R Moos, M., Fontana, A., and Schachner, M. (1991) Astrocyte-derived TGF beta 2 and NGF differentially regulate neural recognition molecule by cultured astrocytes. J. Cell. Biol 115 473–484.Google Scholar
  48. Schmidt-Kastner, R., Szymas, J., and Hossmann, K. A. (1990) Immunohistochemical study of glial reaction and serum-protein extravasation in relation to neuronal damage in rat hippocampus after ischemia. Neuroscience 38, 527–540.PubMedCrossRefGoogle Scholar
  49. Schwartz, M., Sivron, T., Eitan, S., Hirschberg, D. L., Lotan, M., and Elman Faber, A. (1994) Cytokines and cytokine-related substances regulating glial cell response to injury of the CNS. Prog. Brain Res. 103, 331–341.CrossRefGoogle Scholar
  50. Silver, I., Deas, J., and Erecinska, M. (1997) Ion homeostasis in brain cells: differences in intracellular ion responses to energy limitation between cultured neurons and glial cells. Neuroscience 78, 589–601.PubMedCrossRefGoogle Scholar
  51. Steinhauser, C. (1993) Electrophysiologic characteristics of glial cells. Hippocampus 3, 113–123.PubMedCrossRefGoogle Scholar
  52. Strauss, S., Otten, U., Joggerst, B., Pluss, K., and Volk, B. (1994) Increased levels of NGF protein and mRNA and reactive gliosis following kainic acid injection into the rat striatum. Neurosci. Lett 168, 193–196.PubMedCrossRefGoogle Scholar
  53. Sudhalter, J Whithouse, L., Rusche, J. R Marchionni, M. A., and Mahanthappa, N. K. (1996) Schwann cell heparan sulfate proteoglycans play a critical role in glial growth factor/neuroregulin signaling. Glia 17 28–38.Google Scholar
  54. Suzumura, A., Lavi, E., Weiss, S. R., and Silberberg, D. H. (1986) Coronavirus infection induces H-2 antigen expression on oligedendrocytes and astrocytes. Science 232, 991–993.Google Scholar
  55. Traugott, U., and Lebon, P. (1988) Interferon-gamma and Ia antigen are present on astrocytes in active chronic multiple sklerosis lesions. J. Neurol. Sci 84, 257–264.PubMedCrossRefGoogle Scholar
  56. Walz, W., Paterson, I. A., and Wuttke, W. A. (1996) Potassium accumulation in reactive glial cells in situ. Soc. Neurosci. Abstr 22, 1497.Google Scholar
  57. Witte, O W., and Stoll, G. (1997) Delayed and remote effects of focal cortical infarctions. Adv. Neurol 73 207–227.Google Scholar
  58. Yamashita, K., Vogel, P., Fritze, K., Back, T., Hossmann, K. A., and Wiessner, C. (1996) Monitoring the temporal and spatial activation pattern of astroctyes in focal cerebral ischemia using in situ hybridization to GFAP mRNA. Brain Res. 735, 285–297.PubMedCrossRefGoogle Scholar
  59. Yang, H. Y., Lieska, N., Kriho, V., Wu, C. M., and Pappas, G. D. (1997) A subpopulation of reactive astroctyes at the immediate site of cerebral cortical injury. Exp. Neurol 146, 199–205.PubMedCrossRefGoogle Scholar
  60. Yong, V. W., Moumidjian, R., Young, F. P., Ruijs, T. C., Freedman, M. S., Cashman, N., and Antel, J. P. (1991) Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. Proc. Natl. Acad. Sci. USA 88, 7016–7020.Google Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Ronald Jabs
  • Lane K. Bekar
  • Wolfgang Walz

There are no affiliations available

Personalised recommendations