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Metabolic Brain Disease

, Volume 4, Issue 3, pp 213–223 | Cite as

Ammonia-induced swelling of rat cerebral cortical slices: Implications for the pathogenesis of brain edema in acute hepatic failure

  • Robert Ganz
  • Margaret Swain
  • Peter Traber
  • Mauro DalCanto
  • Roger F. Butterworth
  • Andres T. Blei
Original Contributions

Abstract

The pathogenesis of brain edema in fulminant hepatic failure is incompletely understood. Our previous studies in models of this disease suggest the presence of a cytotoxic mechanism; as cortical astrocytes appeared predominantly swollen, we hypothesized that ammonia, metabolized to glutamine solely within this cell, could play a role in brain water accumulation. We determined ammonia levels in different brain regions of rats after hepatic devascularization, a model previously shown to exhibit brain edema. Concentrations of 2.5 mM were observed in the edematous cerebral cortex. We then added several concentrations of ammonium chloride to the first cortical brain slice, a preparation used to study cytotoxic brain edema. At a final bath concentration of ammonia of 5 and 10 mM, swelling could be detected; a decrease in the space of distribution of inulin was seen at the 10 mM concentration, suggesting intracellular water accumulation. Neuropathologically, astrocytes appeared involved even at subswelling doses of ammonia. Octanoic acid, at a 10 mM concentration, also resulted in demonstrable swelling. Ammonia, at concentrations in the incubation bath that approach the levels seen in anin vivo model of brain edema, results in water accumulation of cortical brain slices. Toxins implicated in the pathogenesis of hepatic encephalopathy, such as ammonia and octanoic acid, may, result in brain water accumulation.

Key words

brain edema ammonia octanoic acid fulminant hepatic failure 

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Copyright information

© Plenum Publishing Corporation 1989

Authors and Affiliations

  • Robert Ganz
    • 1
  • Margaret Swain
    • 3
  • Peter Traber
    • 1
  • Mauro DalCanto
    • 2
  • Roger F. Butterworth
    • 3
  • Andres T. Blei
    • 1
  1. 1.Department of MedicineLakeside VA Medical Center and Northwestern UniversityChicago
  2. 2.Department of NeuropathologyLakeside VA Medical Center and Northwestern UniversityChicago
  3. 3.Laboratory of Neurochemistry, “André Viallet” Clinical Research CenterHôpital St. Luc and University of MontrealMontreal

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