Abstract: HepatologyVolume 4, Issue 6 p. 1235-1242 Special ArticlesFree Access The Neurobiology of Hepatic Encephalopathy E. Anthony Jones, Corresponding Author E. Anthony Jones Liver Diseases Section, Digestive Diseases Branch, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20205E. Anthony Jones, Building 10, Room 4D-52, Liver Diseases Section, NIADDK, NIH, Bethesda, Maryland 20205.===Search for more papers by this authorDaniel F. Schafer, Daniel F. Schafer Liver Diseases Section, Digestive Diseases Branch, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20205Search for more papers by this authorPeter Ferenci, Peter Ferenci Liver Diseases Section, Digestive Diseases Branch, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20205Search for more papers by this authorS. Chris Pappas, S. Chris Pappas Liver Diseases Section, Digestive Diseases Branch, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20205Search for more papers by this author E. Anthony Jones, Corresponding Author E. Anthony Jones Liver Diseases Section, Digestive Diseases Branch, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20205E. Anthony Jones, Building 10, Room 4D-52, Liver Diseases Section, NIADDK, NIH, Bethesda, Maryland 20205.===Search for more papers by this authorDaniel F. Schafer, Daniel F. Schafer Liver Diseases Section, Digestive Diseases Branch, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20205Search for more papers by this authorPeter Ferenci, Peter Ferenci Liver Diseases Section, Digestive Diseases Branch, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20205Search for more papers by this authorS. Chris Pappas, S. Chris Pappas Liver Diseases Section, Digestive Diseases Branch, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20205Search for more papers by this author First published: November‐December 1984 https://doi.org/10.1002/hep.1840040624Citations: 52AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 Zieve L. The mechanism of hepatic coma. Hepatology 1981; 1: 360– 365. 2 Zieve L. Hepatic encephalopathy. In: L Schiff, ER Schiff, eds. Diseases of the liver, 5th ed. Philadelphia: J. B. Lippincott Co., 1982: 433– 459. 3 Windus-Podehl G, Lyftogt C, Zieve L, et al. Encephalopathic effect of phenol in rats. J Lab Clin Med 1983; 101: 586– 592. 4 Fischer JE, Baldessarini RJ. False neurotransmitters and hepatic failure. Lancet 1971; 2: 75– 80. 5 Fischer JE, Baldessarini RJ. Pathogenesis and therapy of hepatic coma. In: H Popper, F Schaffner, eds. Progress in liver diseases, Vol V. New York: Grune and Stratton, 1976: 363– 397. 6 James JH, Ziparo V, Jeppsson B, et al. Hyperammonemia, plasma aminoacid imbalance and blood-brain aminoacid transport: a unified theory of portal-systemic encephalopathy. Lancet 1979; 2: 772– 775. 7 Schafer DF, Jones EA. Potential neural mechanisms in the pathogenesis of hepatic encephalopathy. In: H Popper, F Schaffner, eds. Progress in liver diseases. Vol VII. New York: Grune and Stratton, 1982: 615– 627. 8 Conn HO, Lieberthal MM. The hepatic coma syndromes and lactulose. Baltimore: Williams and Wilkins, 1979. 9 E Roberts, TN Chase, DB Tower (Editors). GABA in nervous system function. New York: Raven Press, 1976. 10 P Krogsgaard-Larsen, J Scheel-Kruger, H Kofod (Editors). GABA-neurotransmitters. New York: Academic Press, 1979. 11 P Mandel, FV DeFendis (Editors). GABA–Biochemistry and CNS functions. New York: Plenum Press, 1979. 12 E Costa, G Di Chiara, GL Gessa (Editors). GABA and benzodiazepine receptors. Advances in biochemical psychopharmacology, Vol 26. New York: Raven Press, 1981. 13 Roberts E. The γ-aminobutyric acid (GABA) system and hepatic encephalopathy. Hepatology 1984; 4: 342– 345. 14 Tallman JF, Paul SM, Skolnick P, et al. Receptors for the age of anxiety: pharmacology of the benzodiazepines. Science 1980; 207: 274– 281. 15 Skolnick P, Moncada V, Barker JL, et al. Phenobarbital: dual actions to increase brain benzodiazepine receptor affinity. Science 1981; 211: 1448– 1450. 16 Paul SM, Marangos PJ, Skolnick P. The benzodiazepine-GABA-chloride ionophore receptor complex: common site of minor tranquilizer action. Biol Psychiatry 1981; 16: 213– 229. 17 Study RE, Barker JL. Diazepam and (-)-pentobarbital: fluctuation analysis reveals different mechanisms for potentiation of γ-ami-nobutyric acid responses in cultured neurons. Proc Natl Acad Sci USA 1981; 78: 7180– 7184. 18 Krnjevic K, Phillis JW. Iontophoretic studies of neurones in the mammalian cerebral cortex. J Physiol 1963; 165: 274– 304. 19 Smialowski A. The effect of intra-hippocampal administration of γ-aminobutyric acid (GABA). In: F Fonnum, ed. Amino acids as chemical transmitters. New York: Plenum Press, 1978: 1977– 1980. 20 Blitzer BL, Waggoner JG, Jones EA, et al. A model of fulminant hepatic failure in the rabbit. Gastroenterology 1978; 74: 664– 671. 21 Trewby RN, Casemore C, Williams R. Continuous bipolar recording of the EEG in patients with fulminant hepatic failure. Elec-troenceph Clin Neurophysiol 1978; 45: 107– 110. 22 Sherlock S. Hepatic encephalopathy. In: Diseases of the liver and biliary system, 6th ed. Oxford: Blackwell, 1981: 91– 106. 23 Enna SJ, Snyder SH. A simple, sensitive and specific radioreceptor assay for endogenous GABA in brain tissue. J Neurochem 1976; 26: 221– 224. 24 Ferenci P, Schafer DF, Kleinberger G, et al. Serum levels of gamma-aminobutyric acid-like activity in acute and chronic hepatocellular disease. Lancet 1983; 2: 811– 814. 25 Schafer DF, Fowler JM, Jones EA. Colonic bacteria: a source of γ-aminobutyric acid in blood. Proc Soc Exp Biol Med 1981; 167: 301– 303. 26 Ferenci P, Covell D, Schafer DF, et al. Metabolism of the inhibitory neurotransmitter γ-aminobutyric acid in a rabbit model of fulminant hepatic failure. Hepatology 1983; 3: 507– 512. 27 Oldendorf WH. Brain uptake of radiolabeled amino acids, amines and hexoses after arterial injection. Am J Physiol 1971; 221: 1629– 1639. 28 Horowitz ME, Schafer DF, Molnar P, et al. Increased blood-brain transfer in a rabbit model of acute liver failure. Gastroenterology 1983; 84: 1003– 1011. 29 Livingstone AS, Potvin M, Goresky CA, et al. Changes in the blood brain barrier in hepatic coma after hepatectomy in the rat. Gastroenterology 1977; 73: 687– 704. 30 Balazs R, Cremer JE. Metabolic compartmentalization in the brain. New York: John Wiley and Sons, 1972. 31 Chiappa KH, Ropper AH. Evoked potentials in clinical medicine. N Engl J Med 1982; 306: 1140– 1150, 1205–1211. 32 Schafer DF, Pappas SC, Brody LE, et al. Visual evoked potentials in a rabbit model of hepatic encephalopathy. I. Sequential changes and comparisons with drug-induced comas. Gastroenterology 1984; 86: 540– 545. 33 Cobb WA, Dawson GD. The latency and form in man of the occipital potentials evoked by bright flashes. J Physiol 1960; 152: 108– 121. 34 Purpura DP. Intracellular studies of synaptic organizations in the mammalian brain. In: GD Pappas, DP Purpura, eds. Structure and function of synapses. New York: Raven Press, 1972: 257– 302. 35 Bigler ED. Neurophysiology, neuropharmacology and behavioral relationships of visual system evoked after discharges: a review. Biobehavioral Reviews 1977; 1: 95– 112. 36 Nicoll RA, Madison DV. General anesthetics hyperpolarize neurons in the vertebrate central nervous system. Science 1982; 217: 1055– 1057. 37 Zeneroli ML, Penne A, Parrinello G, et al. Comparative evaluation of visual evoked potentials in experimental hepatic encephalopathy and in pharmacologically induced coma-like states in rat. Life Sci 1981; 28: 1507– 1515. 38 Zeneroli ML, Ventura E, Baraldi M, et al. Visual evoked potentials in encephalopathy induced by galactosamine, ammonia, dimethyldisulfide and octanoic acid. Hepatology 1982; 2: 532– 538. 39 Pappas SC, Ferenci P, Schafer DF, et al. Visual evoked potentials in a rabbit model of hepatic encephalopathy: II. Comparison of hyperammonemic encephalopathy, postictal coma and coma induced by synergistic neurotoxins. Gastroenterology 1984; 86: 546– 551. 40 Bowdler JM, Green AR. Regional rat brain benzodiazepine receptor number and gamma-aminobutyric acid concentration following a convulsion. Br J Pharmacol 1982; 76: 291– 298. 41 Nakayama K. The relationship of visual evoked potentials to cortical physiology. Ann NY Acad Sci 1982; 388: 21– 36. 42 Ferenci P, Pappas SC, Munson PJ, et al. Changes in the status of neurotransmitter receptors in a rabbit model of hepatic encephalopathy. Hepatology 1984; 4: 186– 191. 43 Klotz IM. Numbers of receptor sites from Scatchard graphs: facts and fantasies. Science 1982; 217: 1247– 1249. 44 Laduron P. More binding, more fancy. Trends Pharmacol Sci 1983; 4: 333– 335. 45 Munson PJ, Rodbard D. Number of receptor sites from Scatchard and Klotz graphs: a constructive critique. Science 1983; 220: 979– 981. 46 Munson PJ, Rodbard D. LIGAND: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem 1980; 107: 220– 239. 47 Schafer DF, Fowler JM, Munson PJ, et al. Gamma-aminobutyric acid and benzodiazepine receptors in an animal model of fulminant hepatic failure. J Lab Clin Med 1983; 102: 870– 880. 48 Baraldi M, Zeneroli ML. Experimental hepatic encephalopathy: changes in the binding of 7-aminobutyric acid. Science 1982; 216: 427– 429. 49 Thompson JS, Schafer DF, Schafer GJ, et al. Gamma-aminobutyric acid plasma levels and brain binding in Eck fistula dogs. J Surg Res 1984 (in press). 50 Tran VT, Snyder SH, Major LF, et al. GABA receptors are in creased in the brains of alcoholics. Ann Neurol 1981; 9: 289– 292. 51 Cotman CW, Foster A, Lanthorn T. An overview of glutamate as a neurotransmitter. In: G Di Chiara, GL Gessa, eds. Advances in biochemical psychopharmacology, Vol 27. New York: Raven Press, 1981: 1– 27. 52 Ferenci P, Pappas SC, Munson PJ, et al. Changes in glutamate receptors on synaptic membranes associated with hepatic encephalopathy or hyperammonemia in the rabbit. Hepatology 1984; 4: 25– 29. 53 Baxter JD, Funder JW. Hormone receptors. N Engl J Med 1979; 301: 1149– 1161. 54 Waddington JL, Cross AJ. Denervation supersensitivity of the striatonigral GABA pathway. Nature 1978; 276: 618– 620. 55 Barber RP, Vaughn JE, Saito K, et al. GABA-ergic terminals are presynaptic to primary afferent terminals in substantia gelatinosa of the rat spinal cord. Brain Res 1978; 141: 35– 55. 56 Zeneroli ML, Iuliano E, Racagni G, et al. Metabolism and brain uptake of γ-aminobutyric acid in galactosamine-induced hepatic encephalopathy in rats. J Neurochem 1982; 38: 1219– 1222. 57 Ferenci P, Jacobs R, Pappas, SC, et al. Enzymes of cerebral GABA metabolism and synaptosomal GABA uptake in acute liver failure in the rabbit. Evidence for decreased cerebral GABA-transaminase activity. J Neurochem 1984; 42: 1487– 1490. 58 Baraldi M, Zeneroli ML, Ricci P, et al. Down regulation of striatal dopamine receptors in experimental hepatic encephalopathy. Life Sci 1983; 32: 1417– 1425. 59 Memo M, Lovenberg W, Hanbauer I. Agonist-induced subsensitiv-ity of adenylate cyclase coupled with a dopamine receptor in slices from rat corpus striatum. Proc Natl Acad Sci USA 1982; 79: 4456– 4460. 60 Schafer DF, Jones EA. Hepatic encephalopathy and the γ-aminobutyric acid neurotransmitter system. Lancet 1982; 1: 18– 20. 61 Branch RA, Morgan MH, James J, et al. Intravenous administration of diazepam in patients with chronic liver disease. Gut 1976; 17: 975– 983. Citing Literature Volume4, Issue6November‐December 1984Pages 1235-1242 ReferencesRelatedInformation