Skip to main content
Log in

Ammonia-induced astrocyte swelling in primary culture

  • Original Articles
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The effect of ammonia on water space of astrocytes in culture was determined as a means of studying the neurotoxicity of ammonia in fulminant hepatic failure (FHF). Treatment of primary astrocyte cultures obtained from neonatal rat cortices with 10 mM NH4Cl for 4 days resulted in a 29% increase in astrocytic water space, as measured by an isotopic method utilizing 3-O-methyl-[3H]-glucose. this effect was time- and dose-dependent. The ammonia-induced swelling was reversible as the water space in cultures treated with 10 mH NH4Cl for 3 days, and then returned to normal culture media for 1 day, was similar to control cultures. These findings suggest that elevated levels of ammonia lead to astrocyte swelling and may contribute to the brain edema in FHF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ede, R. J., and Williams, R. 1986. Hepatic encephalopathy and cerebral edema. Semin. Liver Dis. 6:107–118.

    PubMed  Google Scholar 

  2. Livingstone, A. S., Potrin, M., Goresky, C. A., Finlayson, M. H., and Hinchey, E. J. 1977. Changes in the blood-brain barrier in hepatic coma after hepatectomy in the rat. Gastroenterology 73:697–704.

    PubMed  Google Scholar 

  3. Zaki, A. E. O., Ede, R. J., Davis, M., and Williams, R. 1984. Experimental studies of blood-brain barrier permeability in acute hepatic failure. Hepatology 4:359–363.

    PubMed  Google Scholar 

  4. Horowitz, M. E., Schafer, D. F., Molnar, P., Jones, E. A., Blasberg, R. G., Patlak, C. S., Waggoner, J., and Fenstermacher, J. D. 1983. Increased blood brain transfer in a rabbit model of fulminant hepatic failure. Gastroenterology 84:1003–1011.

    PubMed  Google Scholar 

  5. Klatzo, I. 1979. Cerebral oedema and ischemia. Pages 27–39,in Smith, W. T., and Cavanagh, J. B. (eds.), Recent Advances in Neuropathology, Churchill Livingstone, New York.

    Google Scholar 

  6. Canalese J., Gimson, A. E. S., Mellon, P. J., Davis, M., and Williams, R. 1982. Controlled trial of dexamethasone and mannitol for the cerebral edema of fulminant hepatic failure. Gut 23:625–629.

    PubMed  Google Scholar 

  7. Dillon, D., and Schenker, S. 1972. Cerebrospinal fluid protein concentration in hepatic coma. JAMA 221:507.

    PubMed  Google Scholar 

  8. Lo, W. D., Ennis, S. R., Goldstein, G. W., and Betz, A. L. 1987. The effects of galactosamine-induced hepatic failure upon blood-brain barrier permeability. Hepatology. 7:452–456.

    PubMed  Google Scholar 

  9. Knudsen, G. N., Poulsen, H. E., and Paulsen, D. B. 1988. Bloodbrain barrier permeability in galactosamine-induced hepatic encephalopathy. No evidence for increased GABA transport. J. Hepatol. 6:187–192.

    PubMed  Google Scholar 

  10. Kato, M., Sugihara, J., Nakamura, T., and Muto, Y. 1989. Electron microscopic study of the blood-brain barrier in rats with edema and encephalopathy due to acute hepatic failure. Gastroenterol. Jpn. 24:135–142.

    PubMed  Google Scholar 

  11. Seda, H. W. M., Hughes, R. D., Gove, R. D., and Williams, R., 1984. Inhibition of rat brain Na+, K+-ATPase activity by serum from patients with fulminant hepatic falure. Hepatology 4:74–69.

    PubMed  Google Scholar 

  12. Norenberg, M. D. 1977. A light and electron microscopic study of experimental portal-systemic (ammonia) encephalopathy. Progression and reversal of the disorder. Lab. Invest. 36:618–627.

    PubMed  Google Scholar 

  13. Traber, P. G., Dal Canto, M., Ganger, D., and Blei, A. T. 1987. Electron microscopic evaluation of brain edema in rabbits with galactosamine-induced fulminant hepatic failure. Hepatology 7:1257–1261.

    Google Scholar 

  14. Ganz, R., Swain, M., Traber, P., Dal Canto, M., Butterworth, R. F., and Blei, A. T. 1989. Ammonia-induced swelling of rat cerebral cortical slices: Implications for the pathogenesis of brain edema in acute hepatic failure. Metab. Brain Dis. 4:213–223.

    PubMed  Google Scholar 

  15. Conn, H. O., and Lieberthal, M. L. 1979. The Hepatic Coma Syndromes and Lactulose. Williams and Wilkins, Baltimore.

    Google Scholar 

  16. Cooper, A. J. L. and Plum, F. 1987. Biochemistry and physiology of brain ammonia. Physiol. Rev. 67:440–519.

    PubMed  Google Scholar 

  17. Gregorios, J. B., Mozes, L. W., and Norenberg, M. D. 1985. Morphologic effects of ammonia on primary astrocyte cultures. II. Electron microscopic studies. J. Neuropath. Exp. Neurol. 4:404–414.

    Google Scholar 

  18. Norenberg, M. D., Baker, L., Norenberg, L.-O. B., Neary, J. T. 1989. Ammonia-induced astrocyte swelling in primary culture. Trans. Amer. Soc. Neurochem. 20:132.

    Google Scholar 

  19. Gregorios J. B., Mozes, L. W., Norenberg, L.-O. B., and Norenberg, M. D. 1985. Morphologic effects of ammonia on primary astrocyte cultures: I. Light microscopic studies. J. Neuropath. Exp. Nuerol. 44:397–403.

    Google Scholar 

  20. Kletzien, R. F., Pariza, M. W., Becker, J. E., and Potter, V. R. 1975. A method using 3-O-methyl-D-glucose and phloretin for the determination of intracellular water space of cells in monolayer culture. Anal. Biochem. 68:537–544.

    PubMed  Google Scholar 

  21. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.

    PubMed  Google Scholar 

  22. Barres, B. A., Chun, L. L. Y., and Corey, D. P. 1989. Calcium currents in cortical astrocytes: induction by cAMP and neurotrans-mitters and permissive effect of serum factors. J. Neurosci. 9:3169–3175.

    PubMed  Google Scholar 

  23. Hoffmann, E. K., and Simonsen, L. O. 1989. Membrane mechanisms in volume and pH regulation in vertebrate cells Physiol. Rev. 69:315–383.

    PubMed  Google Scholar 

  24. Watson, A. J., Karp, J. E., Walker, W. G., Chamber, T., Risch, V. R., and Brusilow, S. W. 1985. Transient idiopathic hyperammonaemia in adults. Lancet ii:1271–1274

    Google Scholar 

  25. Norenberg, M. D., and Martinez-Hernandez, A. 1979. Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 161:303–310.

    PubMed  Google Scholar 

  26. Neary, J. T., Woodson, C., Blicharska, J., Norenberg, L.-O. B., and Norenberg, M. D. 1909. Effect of ammonia on calcium homeostasis in primary astrocyte cultures. Brain Res. 524:231–235.

    Google Scholar 

  27. Neary, J. T., van Breeman, C., Forster, E., Norenberg, L.-O. B., and Norenberg, M. D. 1988. ATP stimulates calcium influx in primary astrocyte cultures Biochem. Biophys. Res. Commun. 157:1410–1416

    PubMed  Google Scholar 

  28. Norenberg, M. D., Neary, J. T., Baker, L., Blicharska, J., and Norenberg, L.-O. B. 1990. Protection of ammonia-induced swelling in cultured astrocytes. Trans. Amer. Soc. Neurochem. 21:221.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Special issue dedicated to Dr. Santiago Grisolia

Rights and permissions

Reprints and permissions

About this article

Cite this article

Norenberg, M.D., Baker, L., Norenberg, LO.B. et al. Ammonia-induced astrocyte swelling in primary culture. Neurochem Res 16, 833–836 (1991). https://doi.org/10.1007/BF00965694

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00965694

Key Words

Navigation