Abstract
Hepatic encephalopathy (HE) represents one of the most common events in terminal liver failure. Acute HE (fulminant hepatic failure, FHF) presents with the abrupt onset of delirium, seizures, and coma, and has a mortality rate of about 90%. The principal cause of death in FHF is brain edema associated with increased intracranial pressure. Chronic HE, sometimes referred to as portal-systemic encephalopathy, most often occurs in the setting of cirrhosis and is characterized by change in personality, altered mood and behavior, diminished intellectual capacity, abnormal muscle tone and tremor (asterixis), stupor and coma. For reviews, see (Rothstein and Herlong, 1989; Lockwood. 1992).
Keywords
- Hepatic Encephalopathy
- GABAA Receptor
- Fulminant Hepatic Failure
- Neuroactive Steroid
- Pregnenolone Sulfate
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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Abramovitz, M., Homma, H., Ishigaki, S., Tansey, F., Cammer, W., and Listowsky, I., 1988, Characterization and localization of glutathione-S-transferases in rat brain and binding of hormones, neurotransmitters, and drugs, J. Neurochem. 50:50.
Adams, R.D., and Foley, J.M., 1953, The neurological disorder associated with liver disease, Assoc. Res. Nerv. Ment. Dis. Proc. 32:198.
Anderson, R.E., Engstrom, F.L., and Woodbury, D.M., 1984, Localization of carbonic anhydrase in the cerebellum of normal and audiogenic seizure mice, Ann. N. Y Acad. Sci. 429:502.
Anholt, R.R.H., Pedersen, P.L., DeSouza, E.B., and Snyder, S.H., 1986, The peripheral-type benzodiazepine receptor: localization to the mitochondrial outer membrane, J. Biol. Chem. 261:576.
Antkiewicz Michaluk, L., Mukhin, A.G., Guidotti, A., and Krueger, K.E., 1988, Purification and characterization of a protein associated with peripheral-type benzodiazepine binding sites, J. Biol. Chem. 263:17317.
Basile, A.S., Jones, E.A., and Skolnick, P., 1991, The pathogenesis and treatment of hepatic encephalopathy: evidence for the involvement of benzodiazepine receptor ligands, Pharmacol. Rev. 43:27.
Baulieu, E.E.,1991, Neurosteroids: a new function in the brain, Biol. Cell. 71:3.
Belelli, D., Bolger, M.B., and Gee, K.W., 1989, Anticonvulsant profile of the progesterone metabolite 5-α-pregnan-3-α-o1–20-one, Eur. J. Pharmacol. 166:325.
Benavides, J., Quarteronet, D., Imbault, F., Malgouris, C., Uzan, A., Renault, C., Dubroeucq, M.C., Gueremy, C., and Le Fur, G., 1983, Labelling of “peripheral-type” benzodiazepine binding sites in the rat brain by using [3H]PK 11195, an isoquinoline carboxamide derivative: kinetic studies and autoradiographic localization, J. Neurochem. 41:1744.
Bender, A.S., and Hertz, L., 1985, Binding of (3H) Ro5–4864 in primary cultures of astrocytes, Brain Res. 341:41.
Bender, A.S., and Norenberg, M.D., 1996, Effects of ammonia on L-glutamate uptake in cultured astrocytes, Neurochem. Res. 21:567.
Bitran, D., Hilvers, R.J., and Kellog, C.K., 1991, Anxiolytic effects of 3 α-hydroxy-5α[β]-pregnan-20-one: endogenous metabolites of progesterone that are active at the GABA-A receptor, Brain Res. 561:157.
Bologa, L., Sharma, J., and Roberts, E., 1987, Dehydroepiandrosterone and its sulfated derivative reduce neuronal death and enhance astrocytic differentiation in brain cell cultures, J. Neurosci. Res. 17: 274.
Butterworth, R.F., 1991, Pathophysiology of hepatic encephalopathy; the ammonia hypothesis revisited, in: Progress in Hepatic Encephalopathy and Metabolic Nitrogen Exchange, F. Bengtsson, B. Jeppsson, T. Almdal, and H. Vilstrup, eds., CRC Press, Boca Raton.
Butterworth, R.F., 1992, Pathogenesis and treatment of portal-systemic encephalopathy: an update, Dig. Dis. Sci. 37:321.
Cooper, A.J.L., and Plum, F., 1987, Biochemistry and physiology of brain ammonia, Physiol. Rev. 67:440.
Costa, E., and Guidotti, A., 1991, Diazepam binding inhibitor (DBI): a peptide with multiple biological actions, Life Sci. 49:325.
Ducis, I., Norenberg, L.O.B., and Norenberg, M.D., 1988, Effect of ammonia on the benzodiazepine receptor in cultured astrocytes, Soc. Neurosci. Abst. 14:1082.
Ducis, I., Norenberg, L.O.B., and Norenberg, M.D., 1989, Effect of ammonium chloride on the astrocyte benzodiazepine receptor, Brain Res. 499:362.
Fitzpatrick, S.M., Cooper, A.J., and Hertz, L., 1988, Effects of ammonia and (3-methylene-DL-aspartate on the oxidation of glucose and pyruvate by neurons and astrocytes in primary culture, J. Neurochem. 51:1197.
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, Hepatology, 11:371.
Ganz, R., Swain, M., Traber, P., DalCanto, 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.
Garcia-Estrada, J., Del Rio, J.A., Luquin, S., Soriano, E., and Garcia-Segura, L.M., 1993, Gonadal hormones down-regulate reactive gliosis and astrocyte proliferation after a penetrating brain injury, Brain Res. 628:271.
Garcia-Segura, L.M., Luquin, S., Pârducz, A., and Naftolin, F., 1994, Gonadal hormone regulation of glial fibrillary acidic protein immunoreactivity and glial ultrastructure in the rat neuroendocrine hypothalamus, Glia, 10:59.
Gamier, M., Dimchev, A.B.; Boujrad, N., Price, J.M., Musto, N.A., and Papadopoulos, V., 1994, In vitro reconstitution of a functional peripheral-type benzodiazepine receptor from mouse Leydig tumor cells, Mol. Pharmacol. 45:201.
Gee, K.W., 1988, Steroid modulation of the GABA/benzodiazepine receptor-linked chloride ionophore, Malec. Neurobiol. 313:291.
Giguere, J.F., Hamel, E., and Butterworth, R.F., 1992, Increased densities of binding sites for the `peripheral-type’ benzodiazepine receptor ligand [3H]PK 11195 in rat brain following portacaval anastomosis, Brain Res. 585:295.
Guarneri, P., Guarneri, R., Cascio, C., Pavasant, P., Piccoli, F., and Papadopoulos, V., 1994, Neurosteroidogenesis in rat retinas, J. Neurochem. 63:86.
Guarneri, P., Papadopoulos, V., Pan, B., and Costa, E., 1992, Regulation of pregnenolone synthesis in C6–2B glioma cells by 4’-chlorodiazepam, Proc. Natl. Acad. Sci. U. S. A. 89:5118.
Guidotti, A., Forchetti, C.M., Corda, M.G., Konkel, D., Bennett, C.D., and Costa, E., 1983, Isolation and characterization and purification to homogeneity of an endogenous polypeptide with agonistic action on benzodiazepine receptors, Proc. Natl. Acad. Sci. U. S. A. 80:3531.
Harrison, N.L., Majewska, M.D., Harrington, J.W., and Barker, J.L., 1987, Structure activity relationships for steroid interaction with the gamma-aminobutyric acidA receptor complex, J. Pharmacol. Exp. Ther. 241:346.
Hertz, L., McFarlin, D., and Waksman, B., 1990, Astrocytes: auxiliary cells for immune responses in the central nervous system, Immunol. Today, 11:265.
Hertz, L., Murthy, C.R.K., Lai, J.C.K., Fitzpatrick, S.M., and Cooper, A.J.L., 1987, Some metabolic effects of ammonia on astrocytes and neurons in primary culture, Neurochem. Pathol. 6:97.
Hu, Z.Y., Bourreau, E., Jung-Testas, I., Robel, P., and Baulieu, E.-E., 1987, Neurosteroids: oligodendrocyte mitochondria convert cholesterol to pregnenolone, Proc. Natl. Acad. Sci. U. S. A. 84:8215.
Itzhak, Y., Baker, L., and Norenberg, M.D., 1993, Characterization of the peripheral-type benzodiazepine receptor in cultured astrocytes: evidence for multiplicity, Glia, 9:211.
Itzhak, Y., and Norenberg, M.D., 1994a, Attenuation of ammonia toxicity in mice by PK 11195 and pregnenolone sulfate, Neurosci. Lett. 182:251.
Itzhak, Y., and Norenberg, M.D., 1994b, Ammonia-induced upregulation of peripheral-type benzodiazepine receptors in cultured astrocytes labeled with [3H]PK 11195, Neurosci. Lett. 177:35.
Itzhak, Y., Roig-Cantisano, A., Dombro, R.S., and Norenberg, M.D., 1995, Acute liver failure and hyperammonemia increase peripheral-type benzodiazepine receptor binding and pregnenolone synthesis in mouse brain, Brain Res. 705: 345.
Janzer, R.C., and Raff, M.C., 1987, Astrocytes induce blood-brain barrier properties in endothelial cells, Nature, 325: 253.
Jones, E.A., and Schafer, D.F., 1986, Hepatic encephalopathy: a neurochemical disorder, Prog. Liver Dis. 8: 525.
Jung-Testas, I., Hu, Z.Y., Baulieu, E.E., and Robel, P., 1989, Neurosteroids: biosynthesis of pregnenolone and progesterone in primary cultures of rat glial cells, Endocrinology, 125:2083.
Jung-Testas, I., Renoir, M., Bugnard, H., Greene, G.L., and Baulieu, E.-E., 1992, Demonstration of steroid hormone receptors and steroid action in primary cultures of rat glial cells, J. Steroid Biochem. Mol. Biol. 41:621.
Kabbadj, K., EI-Etr, M., Baulieu, E.-E., and Robel, P., 1993, Pregnenolone metabolism in rodent embryonic neurons and astrocytes, Glia, 7:170.
Kato, M., Hughes, R.D., Keays, R.T., and Williams, R., 1992, Electron microscopic study of brain capillaries in cerebral edema from fulminant hepatic failure, Hepatology, 15:1060.
Keyser, D.O., and Pellmar, T.C., 1994, Synaptic transmission in the hippocampus: critical role for glial cells, Glia, 10:237.
Kimelberg, H.K., Jalonen, T., and Walz, W., 1993, Regulation of the brain microenvironment: transmitters and ions, in: Astrocytes: Pharmacology and Function, S. Murphy, ed., Academic Press, San Diego.
Korneyev, A., Guidotti, A., and Costa, E., 1993, Regional and interspecies differences in brain progesterone metabolism, J. Neurochem. 61:2041.
Korneyev, A., Pan, B.S., Polo, A., Romeo, E., Guidotti, A., and Costa, E., 1993, Stimulation of brain pregnenolone synthesis by mitochondrial diazepam binding inhibitor receptor ligands in vivo, J. Neurochem. 61:1515.
Krieger, N.R., and Scott, R.G., 1989, Nonneuronal localization for steroid converting enzyme: 3α-hydroxysteroid oxidoreducatase in olfactory tubercle of rat brain, J. Neurochem. 52:1866.
Krueger, K.E., and Papadopoulos, V., 1990, Peripheral-type benzodiazepine receptors mediate translocation of cholesterol from outer to inner mitochondrial membranes in adrenocortical cells, J. Biol. Chem. 265:15015.
Krueger, K.E., and Papadopoulos, V., 1992, Mitochondrial benzodiazepine receptors and the regulation of steroid biosynthesis, Annu. Rev. Pharmacol. Toxicol. 32:211.
Lambert, J.J., Belelli, D., Hill-Venning, C., and Peters, J.A., 1995, Neurosteroids and GABAA receptor function, Trends Pharmacol. Sci. 16:295.
Lambert, J.J., Peters, J.A., and Cotrell, G.A., 1987, Actions of synthetic and endogenous steroids on the GABAA receptor, Trends Pharmacol. Sci. 8:224.
Lavoie, J., Layrargues, G.P., 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.
Lockwood, A.H., 1992, Hepatic Encephalopathy, Butterworth-Heinemann, Boston.
Macdonald, R.L., and Olsen, R.W., 1994, GABAA receptor channels, Annu. Rev. Neurosci. 17:569.
Majewska, M.D., 1992, Neurosteroids: endogenous bimodal modulators of the GABAA receptor: mechanism of action and physiological significance, Prog. Neurobiol. 38:379.
Majewska, M.D., Demirgoren, S., and London, E.D., 1990, Binding of pregnenolone sulfate to rat brain membranes suggests multiple sites of steroid action action at the GABA-A receptor, Eur. J. Pharmacol. 189:307.
Majewska, M.D., Harrison, N.L., Schwartz, R.D., Barker, J.L., and Paul, S.M., 1986, Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor, Science, 232:1004.
Makar, T.K., Nedergaard, M., Preuss, A., Gelbard, A.S., Perumal, A.S., and Cooper, A.J., 1994, Vitamin E, ascorbate, glutathione, glutathione disulfide, and enzymes of glutathione metabolism in cultures of chick astrocytes and neurons: evidence that astrocytes play an important role in antioxidative processes in the brain, J. Neurochem. 62:45.
Martin, H., Voss, K., Hufnagl, P., Wack, R., and Wassilew, G., 1987, Morphometric and densitometric investigations of protoplasmic astrocytes and neurons in human hepatic encephalopathy, Exp. Pathol. 32:241.
McCarthy, K.D., and Harden, T.K., 1981, Identification of two benzodiazepine binding sites on cells cultured from rat cerebral cortex, J. Pharmacol. Exp. Ther. 216:183.
McEnery, M.W., Snowman, A.M., Trifiletti, R.R., and Snyder, S.H., 1992, Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier, Proc. Natl. Acad. Sci. U. S. A. 89:3170.
Melcangi, R.C., Celotti, F., and Martini, L., 1994, Progesterone 5-α-reduction in neuronal and in different types of glial cell cultures: type 1 and 2 astrocytes and oligodendrocytes, Brain Res. 639: 202.
Mellon, S.H., and. Deschepper, C.F., 1993, Neurosteroid biosynthesis: genes for adrenal steroidogenic enzymes are expressed in the brain, Brain Res. 629:283.
Mennerick, S., and Zorumski, C.F., 1994, Glial contributions to excitatory neurotransmission in cultured hippocampal cells, Nature, 368:59.
Mok, W.M., Herschkowitz, S., and Krieger, N.R., 1991, In vivo studies identify 5a-pregnan-3a-o1–20-one as an active anesthetic agent, J. Neurochem. 57:1296.
Moynagh, P.N., Bailey, C.J., Boyce, S.J., and Williams, D.C., 1991, Immunological studies on the rat peripheral-type benzodiazepine acceptor, Biochem. J. 275:419.
Mukhin, A.G., Papadopoulos, V., Costa, E., and Krueger, K.E., 1989, Mitochondrial benzodiazepine receptors regulate steroid biosynthesis, Proc. Natl. Acad. Sci. U. S. A. 86:9813.
Murthy, C.R., and Hertz, L., 1987, Acute effect of ammonia on branched-chain amino acid oxidation and incorporation into proteins in astrocytes and in neurons in primary cultures, J. Neurochem. 49:735.
Myers, R., Manjil, L.G., Cullen, B.M., Price, G.W., Franckowiak, R.S., and Cremer, J.E., 1991, Macrophage and astrocyte populations in relation to (3H)PK 11195 binding following a local ischemic lesion, J. Cereb. Blood Flow Metab. 11:314.
Nedergaard, M., 1994, Direct signaling from astrocytes to neurons in cultures of mammalian brain cells, Science, 263:1768.
Norenberg, M.D., 1977, A light and electron microscopic study of experimental portal-systemic (ammonia) encephalopathy, Lab. Invest. 36:618.
Norenberg, M.D., 1979, The distribution of glutamine synthetase in the rat central nervous system, J. Histochem. Cytochem. 27:756.
Norenberg, M.D., 1981, The astrocyte in liver disease, in: Advances in Cellular Neurobiology,Vol. 2, S. Fedoroff and L. Hertz, eds., Academic Press, New York.
Norenberg, M.D., 1983, Immunohistochemistry of glutamine synthetase, in: Glutamine, Glutamate, and GABA in the Central Nervous System, L. Hertz, E. Kvamme, E.G. McGeer, and A. Schousboe, eds., Alan R. Liss, New York.
Norenberg, M.D., 1995, Hepatic encephalopathy, in: Neuroglia, H. Kettenmann and B.R. Ransom, eds., Oxford, New York.
Norenberg, M.D. Astrocytic-ammonia interactions in hepatic encephalopathy. Semin. Liver Dis. (In press).
Norenberg, M.D., Baker, L., Norenberg, L.-O.B., Blicharska, J., Bruce-Gregorios, J.H., and Neary, J.T., 1991, Ammonia-induced astrocyte swelling in primary culture, Neurochem. Res. 16:833.
Norenberg, M.D., and Bender, A.S., 1994, Astrocyte swelling in liver failure: role of glutamine and benzodiazepines, Acta Neurochir. 60 (Suppl):24.
Norenberg, M.D., Neary, J.T., Bender, A.S., and Dombro, R.S., 1992, Hepatic encephalopathy: a disorder in glial-neuronal communication, in: Neuronal-Astrocytic Interactions. Implications for Normal and Pathological CNS Function, A.C.H. Yu, L. Hertz, M.D. Norenberg, E. Sykova, and S.G. Waxman, eds., Elsevier, Amsterdam.
Norenberg, M.D., Roig-Cantisano, A., and Itzhak, Y., 1995, Peripheral benzodiazepine receptors and pregnenolone synthesis in models of hepatic encephalopathy and in ammonia-treated astrocytes, J. Neurochem. 64 (Suppl):56.
O’Beirne, G.B., Woods, M.J., and Williams, D.C., 1990, Two subcellular locations for peripheral-type benzodiazepine acceptors in rat liver, Eur. J. Biochem. 188:131.
Olsen, R.W., and Tobin, A.J., 1990, Molecular biology of GABAA receptors, FASEB J. 4:1469.
Papadopoulos, V., and Brown, A.S., 1995, Role of the peripheral-type benzodiazepine receptor and the polypeptide diazepam binding inhibitor in steroidogenesis, J. Steroid Biochem. Mol. Biol. 53:103.
Papadopoulos, V., Guarneri, P., Krueger, K.E., Guidotti, A., and Costa, E., 1992, Pregnenolone biosynthesis in C6–2B glioma cell mitochondria: regulation by a mitochondrial diazepam binding inhibitor receptor, Proc. Natl. Acad. Sci. U. S. A. 89:5113.
Park, C.H., Carboni, E., Wood, P.L., and Gee, K.W., 1996, Characterization of peripheral benzodiazepine type sites in a cultured murine BV-2 microglial cell line, Glia, 16:65.
Parola, A.L., Yamamura, H.I., and Laird, H.E.I., 1993, Peripheral-type benzodiazepine receptors, Life Sci. 52:1329.
Parpura, V., Basarsky, T.A., Liu, F., Jeftinija, K., Jeftinija, S., and Haydon, P.G., 1994, Glutamate-mediated astrocyte-neuron signalling, Nature, 369:744.
Paul, S.M., and Purdy, R.H., 1992, Neuroactive steroids, FASEB J. 6:2311.
Purdy, R.H., Morrow, A.L., Moore, P.H., and Paul, S.M., 1991, Stress-induced elevation of gammaaminobutyric acid type A receptor-active steroids in rat brain, Proc. Natl. Acad. Sci. U. S. A. 88: 4553.
Raabe, W.A., 1989, Neurophysiology of ammonia intoxication, in: Hepatic Encephalopathy: Physiology and Treatment, R.F. Butterworth and G. Pomier Layrargues, eds., Humana Press, Clifton, New Jersey.
Ransom, B.R., and Sontheimer, H., 1992, The neurophysiology of glial cells, J. Clin. Neurophysiol. 9:224.
Rao, V.L.R., Murthy, C.R.K., and Butterworth, R.F.,1992, Glutamatergic synaptic dysfunction in hyperammonemic syndromes, Metab. Brain Dis. 7:1.
Record, C.O., 1991, Neurochemistry of hepatic encephalopathy, Gut, 32:1261.
Risau, W., and Wolburg, H., 1990, Development of the blood-brain barrier, Trends Neurosci. 13:174.
Robel, P., Jung-Testas, I., Hu, Z.Y., Akwa, Y., Sananes, N., Kabbadj, K., Eychenne, B., Sancho, M.J., Kang, K.I., Zucman Morfin, R., and Baulieu, E.E., 1991, Neurosteroids: biosynthesis and metabolism in cultured rodent glia and neurons, in: Neurosteroids and Brain Function, E. Costa and S.M. Paul, eds., Thieme Med Pub, New York.
Romeo, E., Auta, J., Kozikowski, A.P., Ma, D., Papadopoulos, V., Puia, G., Costa, E., and Guidotti, A. 1992, 2-Aryl-3-indoleacetamides (FGIN-1): a new class of potent and specific ligands for the mitochondria] DBI receptor (MDR), J. Pharmacol. Exp. Ther. 262:971.
Rothstein, J.D., and Herlong, H.F., 1989, Neurologic manifestations of hepatic disease, Neurot Clin. 7:563.
Rudge, J.S.,1993, Astrocyte-derived neurotrophic factors, in: Astrocytes. Pharmacology and Function, S. Murphy, ed., Academic Press, San Diego.
Rutishauser, U., 1993, Adhesion molecules of the nervous system, Curr. Opin. Neurobiol. 3:709.
Sawada, J., Kikuchi, Y., Shibutani, M., Mitsumori, K., Inoue, K., and Kasahara, T., 1994, Induction of metallothionein in astrocytes by cytokines and heavy metals, Biol. Signals, 3:157.
Schoemaker, H., Boles, R.G., Horst, D., and Yamamura, H.I., 1983, Specific high-affinity binding sites for [3H]Ro5–4864 in rat brain and kidney, J. Pharmacol. Exp. Ther. 225:61.
Schoemaker, H., Morelli, M., Deshmukh, P., and Yamamura, H.I., 1982, [3H]Ro5–4864 benzodiazepine binding in the kainate lesioned striatum and Huntington’s diseased basal ganglia, Brain Res. 248: 396.
Schousboe, A., 1981, Transport and metabolism of glutamate and GABA in neurons and glial cells, Int. Rev. Neurobiol. 22:1.
Sobel, R.A., DeArmond, S.J., Forno, L.S., and Eng, L.F., 1981, Glial fibrillary acidic protein in hepatic encephalopathy. An immunohistochemical study, J. Neuropathol. Exp. Neurol. 40:625.
Sprengel, R., Werner, P., Seeburg, P.H., Mukhin, A.G., Santi, M.R., Grayson, D.R., Guidotti, A., and Krueger, K.E., 1989, Molecular cloning and expression of cDNA encoding a peripheral-type benzodiazepine receptor, J. Biol. Chem. 264:20415.
Stephenson, D.T., Schober, D.A., Smalstig, E.B., Mincy, R.E., Gehlert, D.R., and Clemens, J.A., 1995, Peripheral benzodiazepine receptors are colocalized with activated microglia following transient global forebrain ischemia in the rat, J. Neurosci. 15:5263.
Swain, M., Butterworth, R.F., and Blei, A.T., 1992, Ammonia and related amino acids in the pathogenesis of brain edema in acute ischemic liver failure in rats, Hepatology, 15:449.
Swain, M.S., Blei, A.T., Butterworth, R.F., and Kraig, R.P., 1991, Intracellular pH rises and astrocytes swell after portacaval anastomosis in rats, Am. J. Physiol. Regul Integr. Comp. Physiol. 261:R1491.
Szerb, J.C., and Butterworth, R.F., 1992, Effect of ammonium ions on synaptic transmission in the mammalian central nervous system, Prog. Neurobiol. 39:135.
Takahashi, H., Koehler, R.C., Brusilow, S.W., and Traystman, R.J., 1991, Inhibition of brain glutamine accumulation prevents cerebral edema in hyperammonemic rats, Am. J. Physiol. Heart Circ. Physiol 261:H825.
Traber, P.G., DalCanto, M., Ganger, D., and Blei, A.T., 1987, Electron microscopic evaluation of brain edema in rabbits with galactosamine-induced fulminant hepatic failure: ultrastructure and integrity of the blood-brain barrier, Hepatology, 7:1272.
Turner, M.M., Ransom, R.W., Yang, J.S., and Olsen, R.W., 1989, Steroid anaesthetics and naturally occurring analogs modulate the gamma-aminobutyric acid receptor complex at a site distinct from barbiturates, J. Pharmacol. Exp. Ther. 248:960.
Verma, A., and Snyder, S.H., 1989, Peripheral type benzodiazepine receptors, Annu. Rev. Pharmacol. Toxicol. 29:307.
Voorhies, T.M., Ehrlich, M.E., Duffy, T.E., Petito, C.K., and Plum, F., 1983, Acute hyperammonemia in the young primate. Physiologic and neuropathological correlates, Pediatric Res., 17:970.
Walz, W., 1989, Role of glial cells in the regulation of the brain ion microenvironment, Prog. Neurobiol. 33: 309.
Westergaard, N., Sonnewald, U., and Schousboe, A., 1995, Metabolic trafficking between neurons and astrocytes: the glutamate glutamine cycle revisited, Dey. Neurosci. 17:203.
Wieland, S., Lan, N.C., Mirasedeghi, S., and Gee, K.W., 1991, Anxiolytic activity of the progesterone metabolite 5a-pregnan-3a-o1–20-one, Brain Res. 565:263.
Zaman, S.H., 1990, Endogenous steroids and pathogenesis of hepatic encephalopathy [letter], Lancet. 336: 573.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Science+Business Media New York
About this chapter
Cite this chapter
Norenberg, M.D., Itzhak, Y., Bender, A.S. (1997). The Peripheral Benzodiazepine Receptor and Neurosteroids in Hepatic Encephalopathy. In: Felipo, V., Grisolía, S. (eds) Advances in Cirrhosis, Hyperammonemia, and Hepatic Encephalopathy. Advances in Experimental Medicine and Biology, vol 420. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5945-0_7
Download citation
DOI: https://doi.org/10.1007/978-1-4615-5945-0_7
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7724-5
Online ISBN: 978-1-4615-5945-0
eBook Packages: Springer Book Archive