Animal Models of Hepatic Encephalopathies

  • Andres T. Blei
  • Reed Omarg
  • Roger F. Butterworth
Part of the Neuromethods book series (NM, volume 22)


Hepatic encephalopathy (HE) is a neuropsychiatric disorder that results from impaired liver function. In humans, hepatic encephalopathy occurs in two major forms: (1) Associated with acute or fulminant hepatic failure, a clinical syndrome resulting from severe inflammatory and/or necrotic liver disease of rapid onset. The neurological disorder progresses from altered mental status to coma, generally within hours or days. Death frequently results from increased intracranial pressure caused by massive brain edema. (2) Portal-systemic encephalopathy (PSE), the most common form of hepatic encephalopathy that accompanies liver cirrhosis. Cirrhosis frequently results from chronic alcohol abuse (at least in Western hemisphere countries) but may also be caused by viral infections, biliary obstruction, drugs, or various toxins. Portal hypertension arises as a result of the cirrhotic process; the high portal pressure stimulates the opening of embryonic venous channels or simply reverses the direction of flow in the existing ones. These shunts permit toxins of intestinal origin to bypass the liver into the systemic circulation; hence the term “portal-systemic encephalopathy.”


Portal Vein Inferior Vena Cava Hepatic Encephalopathy Brain Edema Acute Liver Failure 
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. Adams R. D. and Foley J. M. (1953) The neurological disorder associated with liver disease. Assoc. Res. Nerv. Ment. Dis. Proc. 32, 198–237.Google Scholar
  2. Ariosto F., Riggio O., Cantafora A., Colucci S., Gaudio E., Mechelli C., Merli M., Seri S., and Capocaccia L. (1989) Carbon tetrachloride-induced experimental cirrhosis in the rat: a reappraisal of the model. Eur. Surg. Res. 21, 280–286.PubMedGoogle Scholar
  3. Bassett M. L., Mullen K. D., Scholz B., Fenstermacher J. D., and E. A. Jones (1990) Increased brain uptake of γ-aminobutyric acid in a rabbit model of hepatic encephalopathy. Gastroenterology 98, 747–757.PubMedGoogle Scholar
  4. Beaubernard G, Salomon F., Grange F., Thangapregassam M. J., and Bismuth J. (1977) Experimental hepatic encephalopathy. Changes of the level of wakefulness in the rat with portacaval shunt. Biomedicine 27, 169–171.PubMedGoogle Scholar
  5. Bengtsson F., Gage F. H., Jeppsson B., Nobin A., and Rosengren E. (1985) Brain monoamine metabolism and behavior in portacaval shunted rats. Exp. Neural. 90, 21–35.Google Scholar
  6. Bengtsson F., Bugge M., Vagianos C., Jeppsson B., and Nobin A. (1987) Brain serotonin metabolism and behavior in rats with carbon tetrachloride-induced liver cirrhosis. Res. Exp. Med. 187, 429–438.Google Scholar
  7. Bergeron M., Swain M. S., Reader T. A., Grondin L., and Butterworth R. F. (1990) Effect of ammonia on brain serotonin metabolism in relation to function in the portacaval shunted rat. J. Neurochem. 55, 222–229.PubMedGoogle Scholar
  8. Bergeron M., Pomier Layrargues G., and Butterworth R. F. (1989a) Aromatic and branched-chain amino acids in autopsied brain tissue of cirrhotic patients with hepatic encephalopathy. Metab. Brain Dis. 4, 169–176.PubMedGoogle Scholar
  9. Bergeron M., Reader T. A., Pomier Layrargues G., and Butterworth R. F. (1989b). Monoamines and their metabolites in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. Neurochem. Res. 14, 853–859.PubMedGoogle Scholar
  10. Blakemore A. H., Lord J. W. Jr., and Stefko P. L. (1942) The severed primary artery in the war wounded: a non-suture method of bridging arterial defects. Surgery 12, 488–498.Google Scholar
  11. Blitzer B. L., Waggoner J. G., Jones E. A., Gralnick H. R, Towne D., Butler J., Weise V., Kopin I. J., Walters I., Teychenne P. F., Goodman D. G., and Berk P. D. (1978) A model of fulminant hepatic failure in the rabbit. Gastroenterology 74, 664–671.PubMedGoogle Scholar
  12. Bollman J. L., and van Hook E. (1968) A simplified two-stage hepatectomy in the rat. J. Appl. Physiol. 24, 722–723.PubMedGoogle Scholar
  13. Bugge M., Bengtsson F., Nobin A., Jeppsson B., and Herlin P. (1986) Metabolism of monoamines in the brain after total hepatectomy in the rat. Ext. Neurol. 94, 11–20.Google Scholar
  14. Bures J., Buresova D., and Huston J. (1976) Techniques and Basic Experiments for the Study of Brain and Behavior. Elsevier, Amsterdam, pp. 37–50.Google Scholar
  15. Butterworth R. F. and Giguère J. F. (1986) Cerebral amino acids in portal-systemic encephalopathy: lack of evidence for altered γ-aminobutyric acid (GABA) function. Metab. Brain Dis. 1, 221–228.PubMedGoogle Scholar
  16. Butterworth R. F., Giguère J. F., Michaud J., and Pomier Layrargues G. (1987) Ammonia: key factor in the pathogenesis of hepatic encephalopathy. Neurochem. Pathol. 6, 1–12.PubMedGoogle Scholar
  17. Butterworth R. F., Girard G., and Giguère J. F. (1988) Regional differences in the capacity for ammonia removal by brain following portacaval anastomosis. J. Neurochem. 51, 486–490.PubMedGoogle Scholar
  18. Butterworth R. F., Lavoie J., Giguère J. F., and Pomier Layrargues G. (1988) Affinities and densities of high-affinity [3H]-muscimol (GABA-A) binding sites and central benzodiazepine receptors are unchanged in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. Hepatology 8, 1084–1088.PubMedGoogle Scholar
  19. Butterworth R. F. and Pomier Layrargues G. (1990) Benzodiazepine receptors and hepatic encephalopathy. Hepatology 11, 499–501.PubMedGoogle Scholar
  20. Butterworth R. F., Tonon M. C., Desy L., Giguère J. R., Vaudry H., and Pelletier G. (1991a) Increased brain content of the endogenous benzodiazepine receptor ligand octadecaneuropeptide (ODN) following portacaval anastomosis in the rat. Peptides 12, 119–125.PubMedGoogle Scholar
  21. Butterworth R. F., Le O., Lavoie J., and Szerb J. C. (1991b) Effect of portacaval anastomosis on electrically stimulated release of glutamate from rat hippocampal slices. J. Neurochem. 56, 1481–1484.PubMedGoogle Scholar
  22. Chamuleau R. A. F. M., Deutz N. E. P., De Haan J. G., and Van Gool J. (1987) Correlation between electroencephalographic and biochemical indices in acute hepatic encephalopathy in rats. J. Hepatol. 4, 299–306.PubMedGoogle Scholar
  23. Chirito E., Lister C., and Chang T. M. S. (1979) Biochemical, hematological and histological changes in a fulminant hepatic failure rat model for artificial liver assessment. Artif. Organs 3, 42–46.PubMedGoogle Scholar
  24. Chojkier M. and Fierer J. (1985) D-galactosamine hepatotoxicity is associated with endotoxin sensitivity and mediated by lymphoreticular cells in mice. Gastroenterology 88, 115–121.PubMedGoogle Scholar
  25. Conn H. O. (1988) The Hepatic Encephalopathies, in Hepatic Encephalopathy: management with lactulose and related carbohydrates (Conn H. O. and Bircher J., eds.), Medi-Ed Press, East Lansing, MI, pp. 3–14.Google Scholar
  26. Cooper A. and Plum F. (1987) Biochemistry and physiology of ammonia. Physiol. Rev. 67, 490–519.Google Scholar
  27. Coy D., Srivastava A., Gottstein J., Butterworth R. F., and Blei A. T. (1991) Postoperative course after portacaval anastomosis is determined by the portacaval pressure gradient. Am. J. Physiol. 261, G1072–G1078.PubMedGoogle Scholar
  28. Crinquette J. F., Boschat M., Rapin J. R., Delorme M. L., and Opolon P. (1982) Early changes in blood-brain barrier permeability after porto-caval shunt and liver ischemia. Clin. Physiol. 2, 241–250.PubMedGoogle Scholar
  29. Degas F., Degas J. D., Bourdiau D., Peignoux M., Prandi D., Roche-Sicot J., Sicot C., Rueff B., and Benhamou J. P. (1974) Experimental acute hepatic encephalopathy: Comparison of the electroencephalographic changes in the liverless and in the eviscerated rat. Clin. Sci Mol. Med. 47, 599–608.Google Scholar
  30. DeGroot G. H., Reuvers C. B., Schalm S. W., Boks A. L., Terpstra O. T., Jeekel H., Ten Kate F. W., and Bruinvels J. (1987) A reproducible model of acute hepatic failure by transient ischemia in ihe pig. J. Surg. Res. 42, 92–100.Google Scholar
  31. Diaz-Munoz M. and Tapia R. (1988) Regional brain GABA metabolism and release during hepatic coma preduced in rats chronically treated with carbon tetrachloride. Neurohcem. Res. 13, 37–44.Google Scholar
  32. Dixit V. and Chang T. M. S. (1990) Brain edema and the blood brain barrier in galactosamine-induce fulminant hepatic failure rats. ASAIO Trans. 36, 21–27.PubMedGoogle Scholar
  33. Ede R. J., Gove C. D., Hughes R. D., Marshall W., and Williams R. (1987) Reduced brain Na+, K+-ATPase activity in rats with galactosamine-induced hepatic failure: relationship to encephalopathy and cerebral oedema. Clin Sci. 72, 365–371.PubMedGoogle Scholar
  34. Ede R. J. and Williams R. (1986) Hepatic encephalopathy and cerebral edema. Sem. Liver Dis. 6, 107–118.Google Scholar
  35. Fick T. E., Schalm S. W., and De Vlieger M. (1987) A surgical model of fulminant hepatic failure in the rabbit: different effects of end-to-side versus small-diameter side-to-side portacaval shunt. Eur. Surg. Res. 19, 276–282.PubMedGoogle Scholar
  36. Francavilla A., Makowka L., Polimeno L., Barone M., Demetris J., Prelich J., Van Thiel D. H., and Starzl T. E. (1989) A dog model for acetaminophen-induced fulminant hepatic failure. Gastroenterology 96, 470–478.PubMedGoogle Scholar
  37. Funovics J. M., Cummings M. G., Shuman L., James J. H., and Fischer J. E. (1975) An improved non-suture method for portacaval anastomosis in the rat. Surgery 77, 661–664.PubMedGoogle Scholar
  38. Gazzard B. G., Hughes R. D., Mellon P. J., Portmann B., and Williams R. (1975) A dog model of fulminant hepatic failure produced by paracetamol administration. Br. J Exp. Pathol. 56, 408–411.PubMedGoogle Scholar
  39. Gammal S. H., Basile A. S., Geller D., Skolnick P., and Jones E. A. (1990) Reversal of the behavioral and electrophysiological abnormalities of an animal model of hepatic encephalopathy by benzodiazepine receptor ligands. Hepatalogy 11, 371–378.Google Scholar
  40. Geller D., Gammal S. H., Mullen K. D., and Jones E. A. (1988) An improved rat model of hepatic encephalopathy due to fulminant hepatic failure: the importance of supportive therapy. Advances in Ammonia Metabolism and Heptic Encephalopathy (Soeters P. B. et al., eds.), Elsevier, Amsterdam, 213–217.Google Scholar
  41. Giges B., Dein H. L., Sborov V. H,, Selijson D., and Howard J. N. (1953) Experimental hepatic coma. Surg. Gynecol. Obstet. 97, 763–771.PubMedGoogle Scholar
  42. Giguère J. F. and Butterworth R. F. (1984) Amino acid changes in regions of the CNS in relation to function in experimental portalsystemic encephalopathy. Neurochem. Res. 9, 1309–1321.PubMedGoogle Scholar
  43. Giguère J. F., Besnard A. M., Lavoie J., Pomier Layrargues G., and Butterworth R. F. (1989) Activities of glutamate-related enzymes in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. Hepatic Encephalopathy: Pathophysiology and Treatment (Butterworth R. F. and Pomier Layrargues G., eds.), Humana, Clifton, NJ, pp. 435–445.Google Scholar
  44. Hanid N. A., MacKenzie R. L., Jenner R. E., Chase R. A., Mellon P. J., Trewby P. N., Janota I., Davis M., Silk D. B. A., and Williams R. (1979) Intracranial pressure in pigs with surgically induced liver failure. Gastroenterology 76, 123–131PubMedGoogle Scholar
  45. Hawkins R. A., Mans A. M., and Biebuyck J. F. (1987) Changes in brain metabolism in hepatic encephalopathy. Newchem. Pathol 6, 35–66.Google Scholar
  46. Herlin P. and Holmin T. (1984) Surgical models of acute liver failure. Advances in Hepatic Encephalopathy and Urea Cycle Disease (Kleinberger G. and Ferenci P., eds.), Karger, Basel 62–67.Google Scholar
  47. Hindfelt B., Plum F., and Duffy T. E. (1977) Effects of acute ammonia intoxication on cerebral metabolism in rats with portacaval shunts. J. Clin. Invest. 59, 386–396.PubMedGoogle Scholar
  48. Holmin T. (1976) The effect of hepatectomy on the energy state and on acid-base variables of the rat brain. Scan. J. Clin. Lab. Invest. 36, 423–429.Google Scholar
  49. Horowitz M. E., Schafer D. F, and Molnar P. (1983) Increased blood-brain transfer in a rabbit model of acute liver failure. Gastroenterology 84, 1003–1011.PubMedGoogle Scholar
  50. Huet P. M., Pomier Layrargues G., Duguay L., and Du Souich P. (1981) Blood-brain transport of tryptophan and phenylalanine: effect of portacaval shunt in dogs. Am. J Physiol. 241, G163–G169.PubMedGoogle Scholar
  51. Jellinger K. and Riederer P. (1977) Brain monoamines in metabolic (endotoxic) coma. A preliminary biochemical study in human postmortem material. J. Neurol. Trans 43, 275–286.Google Scholar
  52. Jenkins A. A. and Steele R. D. (1988) Diet composition and surgical technique influences the post operative recovery of portacaval shunted rats. Hepatology 8, 855–860.Google Scholar
  53. Jones B. D., Mullen K. D., Rossle M., Maynard T., and Jones E. A. (1987) Hepatic encephalopathy: application of visual evoked responses to test hypotheses of its pathogenesis in rats. J. Hepatol. 4, 118–126.PubMedGoogle Scholar
  54. Kato M., Sugihara J., Nakamura T., and Muto Y. (1989) Electron microscopic study of the blood-brain barrier in rats with brain edema and encephalopathy due to acute hepatic failure. Gastroenterol. Japon. 24,2, 135–142.Google Scholar
  55. Keppler D., Lesch R., Reutter W., and Decker K. (1968) Experimental hepatitis induced by D.-galactosamine. Exp. Mol. Pathol. 9, 279–290.PubMedGoogle Scholar
  56. Knudsen G. M., Paulsen H, E., and Paulson O. B. (1988) Blood-brain barrier permeability in the galactosamine-induced hepatic encephalopathy. J. Hepatol. 6, 187–192.PubMedGoogle Scholar
  57. Lavoie J., Giguère J. F., Pomier Layrargues G., and Butterworth R. F. (1987a) Amino acid changes in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. J. Neurochem. 49, 692–697.PubMedGoogle Scholar
  58. Lavoie J., Giguère J. F., Pomier Layrargues G., and Butterworth R. F. (1987b) Activities of neuronal and astrocytic marker enzymes in autopsied brain tissue from patients with hepatic encephalopathy. Metab. Brain Dis. 2, 283–290.PubMedGoogle Scholar
  59. Lavoie J., Pomier Layrargues G., and Butterworth R. F. (1990) Increased densities of peripheral-type benzodiazepine receptors in brain autopsy samples from cirrhotic patients with hepatic encephalopathy. Hepatology 11, 874–878.PubMedGoogle Scholar
  60. Le Provost C., Virelizier J. L., and Duprey J. M. (1975) Immunology of MHV-3 infection. III. Clinical and virologic observations of a persistent viral infection. J. Immunol. 115, 640–643.Google Scholar
  61. Lee S. H. and Fisher B. (1961) Portacaval shunt in the rat. Surgery 50, 668–672PubMedGoogle Scholar
  62. Livingstone A. S., Potvin 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.PubMedGoogle Scholar
  63. Lo W. D., Ennis S. R., Goldstein G. W., McNeely D. L., and Betz A. L. (1987) The effects of galactosamine-induced hepatic failure upon blood-brain barrier permeability. Hepatology 7, 452–456.PubMedGoogle Scholar
  64. Maddison J. E., Dodd P. R., Morrison M., Johnston G. A. R., and Farrell G. C. (1987) Plasma GABA, GABA-like activity and the brain GABA-benzo-diazepine receptor complex in rats with chronic hepatic encephalopathy. Hepatology 7, 621–628.PubMedGoogle Scholar
  65. Miller-Berghaus G., Reuter C., and Bleyl U. (1976) Experimental galactosamine-induced hepatitis. Effect of anticoagulant and antifibrinolytic agents on microclot formation. Am. J. Pathol. 82, 393–406.Google Scholar
  66. Mullen K. D., Schafer D. F., Cuchi P., Rossle M., Maynard J. F., and Jones E. A. (1988) Evaluation of the suitability of galactosamine-induced fulminant hepatic failure as a model of hepatic encephalopathy in the rat and the rabbit. In Advances in Ammonia Metabolism and Hepatic Encephalopathy (Soeters P. B. et al., eds.), Elsevier, Amsterdam, pp. 205–211.Google Scholar
  67. Norenberg M. D., Lapham L. W., Nichols F. A., and May A. G. (1974) An experimental model for the study of hepatic encephalopathy. Arch. Neurol. 31, 106–109.PubMedGoogle Scholar
  68. Okamoto H., Fujimura T., and Yashiro K. (1985) Correlation between electroencephalogram, hepatic encephalopathy grade and biochemical indices in beagles with portacaval anastomosis. J. Parent and Ent. Nutr. 9, 326–333.Google Scholar
  69. Olasmaa M., Rothstein J. D., Guidotti A., Weber R. J., Paul S. M., Spector S., Zeneroli M. L., Baraldi M., and Costa E. (1990) Endogenous benzodiazepine receptor ligands in human and animal hepatic encephalopathy. J. Neurochem. 55, 2015–2023.PubMedGoogle Scholar
  70. Opolon P., Lavallard M. C., Huguet C. L., Bidallier M., Granger A., Gallot D., and Bloch P. (1976) Hemodialysis versus cross hemodialysis in experimental hepatic coma. Surg. Gyn. Obst. 142, 845–854.PubMedGoogle Scholar
  71. Ortega L., Landa Garcia J. I., Torres Garcia A., Silecchia G., Arenas J., Suarez A., Moreno Azcoitia M., Sanz Esponera J., Moreno Gonzalez E., and Balibrea Cantero J. L. (1985) Acetaminophen-induced fulminant hepatic failure in dogs. Hepatology 5, 673–676.PubMedGoogle Scholar
  72. Pappas S. C., Ferenci P., Schafer D. F., and Jones E. A. (1984) Visual evoked potentials in a rabbit model of hepatic encephalopathy. Gastroenterology 86, 546–551.PubMedGoogle Scholar
  73. Pappas S. C., Levy G., Gordon V. P., Nakatsukasa H., and Martin P. (1988) The GABA hypothesis of hepatic encephalopathy: further studies in multiple animal models. In Advances in Ammonia Metabolism and Hepatic Encephalopthy (Soeters P. B. et al., eds.), Elsevier, Amsterdam, pp. 258–264.Google Scholar
  74. Peignoux M., Bernuau J., and Benhamou J. F. (1982) Total hepatectomy and hepatic vascular exclusion in the rat. A comparison with special reference to the influence of body temperature. Clin. Sci. 62, 273–277.PubMedGoogle Scholar
  75. Peterson C., Giguère J. F., Cotman C. W., and Butterworth R. F. (1990) Selective loss of N-methyl-D-aspartate-sensitive L-3H-glutamate binding sites in rat brain following portacaval anastomosis. J. Neurochem. 55, 386–390.PubMedGoogle Scholar
  76. Pluta R. and Albrecht J. (1984) Thioacetamide-induce hepatic encephalopathy in the rat, Neuropathol. Pol. 22, 379–385.Google Scholar
  77. Pluta R. and Albrecht J. (1986) Changes in arterial and cerebral venous blood gases, cerebral blood flow and cerebral oxygen consumption at different stages of thioacetamide-induced hepatogenic encephalopathy in rat. Resuscitation 14, 135–139.PubMedGoogle Scholar
  78. Pomier Layrargues G., Roy S., Lavoie J., Butterworth R. F., and Huet P. M. (1988) GABAergic function in dogs with hepatic encephalopathy associated with cirrhosis or portacaval shunt. In Adv. Ammonia Metab and Hepatic Enceph. (Soeters P. B., Wilson J. H. P., Meijer A. J., and Holm E., eds.), Elsevier, Amsterdam, pp. 225–280Google Scholar
  79. Potvin M., Morrison H., Finlayson E., Lough J. O., and Goresky C. A. (1984) Cerebral abnormalities in hepatectomized rats with acute hepatic coma. Lab. Invest. 50, 560–564.PubMedGoogle Scholar
  80. Proctor E. and Chatamra K. (1984) Standardized micronodular cirrhosis in the rat. Eur. Surg. Res. 16, 182–186.PubMedGoogle Scholar
  81. Record C. O., Buxton B., Chase R. A., Curzon G., Murray-Lyon I. M., and Williams R. (1976) Plasma and brain amino acids in fulminant hepatic failure and their relationship to hepatic encephalopathy. Eur. J. Clin. Invest. 6, 387–394.PubMedGoogle Scholar
  82. Rössle M., Deckert J., and Jones E. A. (1989) Autoradiographic analysis of GABA-benzodiazepine receptors in an animal model of acute hepatic encephalopathy. Hepatology 10, 143–148.PubMedGoogle Scholar
  83. Rzepczynski D., Zieve L., Lindblad S., and LaFontaine D. (1986) In vivo studies of GABAergic effects in experimental hepatic encephalopathy. Hepatology 6, 902–905.PubMedGoogle Scholar
  84. Schafer D. F., Pappas S. C., Brody L. E., Jacobs R., and Jones E. A. (1984) Visual evoked potentials in a rabbit model of hepatic encephalopathy. Gastroenterology 86, 540–545.PubMedGoogle Scholar
  85. Schafer D. F. (1984) Toxin models of acute liver failure. In Advances in Hepatic Encephalapathy and Urea Cycle Disease (Kleinberger G. and Ferenci P., eds.), Karger, Basel, 57–61.Google Scholar
  86. Schafer D. F. and Jones E. A. (1982) Hepatic encephalopathy and the μ-aminobutyric acid neurotransmitter system. Lancet 1, 18–20.PubMedGoogle Scholar
  87. Sicot J. R., Sicot C., Peignoux M., Bourdiau D., Degos F., Degos J. D., Prandi D., Rueff B., and Benhamou J. P. (1974) Acute hepatic encephalopathy in the rat: the effect of cross-circulation. Clin. Sci. Mol. Med. 47, 609–615.PubMedGoogle Scholar
  88. Soeters P. B., Weir G., Ebeid A. M., and Fischer J. E. (1977) Insulin, glucagon, portal-systemic shunting and hepatic failure in the dog. J. Surg. Res. 23, 183–188.PubMedGoogle Scholar
  89. Steindl P., Puspok A., Druml W., and Ferenci P. (1991) Beneficial effect of pharmacological modulation of the GABAA-benzodiazepine receptor on hepatic encephalopathy in the rat: comparison with uremic encephalopathy. Hepatology 14, 963–968.PubMedGoogle Scholar
  90. Swain M., Butterworth R. F., and Blei A. T. (1990) Brain ammonia and related amino acids in the pathogenesis of brain edema in acute liver failure. Hepatology 12(4), 858 (abst).Google Scholar
  91. Terblanche J., Hickman R., Miller D. J., Fradter R., and Saunders S. J. (1975) Animal experience with support systems: are there appropriate animal models of fulminant hepatic necrosis? In Artificial Liver Support (Williams R., and Murray-Lyons I.), Pitman Medical, London, M163–172.Google Scholar
  92. Thompson J. S., Schafer D. F., Schafer G. J., and Hodgson P. E. (1985) γ-aminobutyric acid plasma levels and brain binding in Eck Fistula dogs. J. Sura. Res. 38, 143–148.Google Scholar
  93. Tonnesen K. and Balling H. (1986) Cerebral flow and metabolism in experimental liver failure. Acta Chir. Scand. 152, 439–445.PubMedGoogle Scholar
  94. Traber P. G., Ganger D. R., and Blei A. T. (1986) Brain edema in rabbits with galactosamine-induced fulminant hepatitis. Gastroenterology 91, 1347–1356.PubMedGoogle Scholar
  95. 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, 1272–1277.PubMedGoogle Scholar
  96. Traber P., Dal Canto M., Ganger D., and Blei A. T. (1989) Effect of body temperature on brain edema and encephalopathy in the rat after hepatic devascularization. Gastroenterology 96, 885–891.PubMedGoogle Scholar
  97. Tyce G. M., Flock E. V., and Owen C. A. (1971) Metabolism of glucose in brain after hepatectomy. Exp. Biol. Med. 4, 92–103.PubMedGoogle Scholar
  98. Van der Rijt C. C. D., De Knegt R. J., Schalm S. W., Terpstra O. T., and Mechelse K. (1990). Flumazenil does not improve hepatic encephalopathy associated with acute liver failure in the rabbit. Metab. Brain Dis. 5, 131–142.PubMedGoogle Scholar
  99. Van Niekerk J. L. M. and Koopman J. P. (1986) Portacaval shunt in the rabbit, a model for encephalopathy. Z. Versuchstierkd. 28, 7–9.PubMedGoogle Scholar
  100. Watanabe A., Higashi T., and Nagashima H. (1979) An animal model of fulminant hepatic failure in the rat. Acata Medica Okayama 33, 443–450.Google Scholar
  101. Webster S., Gottstein J., Levy R., and Blei A. T. (1991) Intracranial pressure waves and intracranial hypertension in rats with ischemic acute liver failure. Hapatology 14, 715–720.Google Scholar
  102. Winduss-Podehl G., Lyftogt C., Zieve L., and Brunner G. (1983) Encephalopathic effect of phenol in rats. J. Lab. Clin. Med. 101, 586–592.Google Scholar
  103. Yamaguchi Y., Bollinger R. R., Defaria E., Landis B., and Quarfordt S. (1989) A simplified single stage total hepatectomy in the rat with maintenance of gastrointestinal absorptive function. Hepatology 9, 69–74.PubMedGoogle Scholar
  104. Yamamoto H. and Sugihara N. (1987) Blood ammonia levels and hepatic encephalopathy induced by CCl4 in rats. Toxicol. and Applied Pharmacol. 91, 461–468.Google Scholar
  105. 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.PubMedGoogle Scholar
  106. Zeneroli M. L., Ventura E., Baraldi M., Penne A., Messori E., and Zieve L. (1982) Visual evoked potentials in encephalopathy induced by galactosamine, ammonia, dimethyldisulfide and octanoic acid. Hepatology 2, 532–538.PubMedGoogle Scholar
  107. Zeneroli M. L. (1985) Hepatic encephalopathy—experimental studies in a rat model of fulminant hepatic failure. J. Hepatol 1, 301–312.PubMedGoogle Scholar
  108. Zieve L. (1987) Pathogenesis of hepatic encephalopathy. Met. Brain Dis. 2, 147–166.Google Scholar
  109. Zieve L., Doizaki W. M., and Lyftogt C. (1984) Brain methanethiol and ammonia concentrations in experimental hepatic coma and coma induced by injection of combination of these substances. J Lab. Clin Med. 104, 665–674.Google Scholar
  110. Zimmerman C., Ferenci P., Pifl C., Yurdaydin, C., Ebner J., Lassmann H., Roth E., and Hortnagl H. (1989) Hepatic encephalopathy in thioacetamide-induced acute liver failure in rats: characterization of an improved model and study of amino acid-ergic neurotransmission. Hepatology 9, 594–601.Google Scholar

Copyright information

© The Humana Press Inc 1992

Authors and Affiliations

  • Andres T. Blei
    • 1
  • Reed Omarg
    • 1
  • Roger F. Butterworth
    • 2
  1. 1.Division of GastroenterologyVA Hospital and Northwestern UniversityChicago
  2. 2.Laboratory of NeurochemistryUniversity of MontrealQuebecCanada

Personalised recommendations