Pathogenetic interplay between osmotic and oxidative stress: the hepatic encephalopathy paradigm

References

Bai, G., Rama-Rao, K.V., Murthy, C.R., Panickar, K.S., Jayakumar, A.R., and Norenberg, M.D. (2001). Ammonia induces the mitochondrial permeability transition in primary cultures of rat astrocytes. J. Neurosci. Res.66, 981–991.10.1002/jnr.10056Search in Google Scholar

Bender, A.S. and Norenberg, M.D. (1998). Effect of benzodiazepines and neurosteroids on ammonia-induced swelling in cultured astrocytes. J. Neurosci. Res.54, 673–680.10.1002/(SICI)1097-4547(19981201)54:5<673::AID-JNR12>3.0.CO;2-PSearch in Google Scholar

Bender, A.S., Rivera, I.V., and Norenberg, M.D. (1992). Tumor necrosis factor α induces astrocyte swelling. Trans. Am. Soc. Neurochem.23, 113.Search in Google Scholar

Bender, A.S., Schousboe, A., Reichelt, W., and Norenberg, M.D. (1998). Ionic mechanisms in glutamate-induced astrocyte swelling: role of K⁺ influx. J. Neurosci. Res.52, 307–321.10.1002/(SICI)1097-4547(19980501)52:3<307::AID-JNR7>3.0.CO;2-HSearch in Google Scholar

Benz, B., Grima, G., and Do, K.Q. (2004). Glutamate-induced homocysteic acid release from astrocytes: possible implication in glia-neuron signaling. Neuroscience124, 377–386.10.1016/j.neuroscience.2003.08.067Search in Google Scholar

Bezzi, P., Domercq, M., Vesce, S., and Volterra, A. 2001. Neuron-astrocyte cross-talk during synaptic transmission: physiological and neuropathological implications. Prog. Brain Res.132, 255–265.Search in Google Scholar

Blei, A.T. (2004). Infection, inflammation and hepatic encephalopathy, synergism redefined. J. Hepatol.40, 327–330.10.1016/j.jhep.2003.12.007Search in Google Scholar

Braissant, O., Honegger, P., Loup, M., Iwase, K., Takiguchi, M., and Bachmann, C. (1999). Hyperammonemia: regulation of argininosuccinate synthetase and argininosuccinate lyase genes in aggregating cell cultures of fetal rat brain. Neurosci. Lett.266, 89–92.10.1016/S0304-3940(99)00274-8Search in Google Scholar

Brand, A., Leibfritz, D., and Richter-Landsberg, C. (1999). Oxidative stress-induced metabolic alterations in rat brain astrocytes studied by multinuclear NMR spectroscopy. J. Neurosci. Res.58, 576–585.10.1002/(SICI)1097-4547(19991115)58:4<576::AID-JNR10>3.0.CO;2-DSearch in Google Scholar

Buchczyk, D.P., Grune, T., Sies, H., and Klotz, L.O. (2003). Modifications of glyceraldehyde-3-phosphate dehydrogenase induced by increasing concentrations of peroxynitrite: early recognition by the 20S proteasome. Biol. Chem.384, 237–241.10.1515/BC.2003.026Search in Google Scholar

Busch, G.L., Wiesinger, H., Gulbins, E., Wagner, H.J., Hamprecht, B., and Lang, F. (1996). Effect of astroglial cell swelling on pH of acidic intracellular compartments. Biochim. Biophys. Acta1285, 212–218.10.1016/S0005-2736(96)00163-0Search in Google Scholar

Cassina, P., Peluffo, H., Pehar, M., Martinez-Palma, L., Ressia, A., Beckman, J.S., Estevez, A.G., and Barbeito, L. (2002). Peroxynitrite triggers a phenotypic transformation in spinal cord astrocytes that induces motor neuron apoptosis. J. Neurosci. Res.67, 21–29.10.1002/jnr.10107Search in Google Scholar

Chamberlin, M.E. and Strange, K. (1989). Anisosmotic cell volume regulation: a comparative view. Am. J. Physiol.257, C159–C173.10.1152/ajpcell.1989.257.2.C159Search in Google Scholar

Clark, E.C., Thomas, D., Baer, J., and Sterns, R.H. (1996). Depletion of glutathione from brain cells in hyponatremia. Kidney. Int.49, 470–476.10.1038/ki.1996.66Search in Google Scholar

Cordoba, J., Alonso, J., Rovira, A., Jacas, C., Sanpedro, F., Castells, L., Vargas, V., Margarit, C., Kulisewsky, J., Esteban, R., and Guardia, J. (2001). The development of low-grade cerebral edema in cirrhosis is supported by the evolution of ¹H-magnetic resonance abnormalities after liver transplantation. J. Hepatol.35, 598–604.10.1016/S0168-8278(01)00181-7Search in Google Scholar

Cordoba, J., Crespin, J., Gottstein, J., and Blei, A.T. (1999). Mild hypothermia modifies ammonia-induced brain edema in rats after portacaval anastomosis. Gastroenterology116, 686–693.10.1016/S0016-5085(99)70191-5Search in Google Scholar

Delavoie, F., Li, H., Hartwick, M., Robert, J.C., Giatzakis, C., Peranzi, G., Yao, Z.X., Macario, J., Lacapere, J.J., and Papadopoulos, V. (2003). In vivo and in vitro peripheral-type benzodiazepine receptor polymerization: functional significance in drug ligand and cholesterol binding. Biochemistry42, 4506–4519.10.1021/bi0267487Search in Google Scholar

Dombro, R.S., Bender, A.S., and Norenberg, M.D. (2000). Association between cell swelling and glycogen content in cultured astrocytes. Int. J. Dev. Neurosci.18, 161–169.10.1016/S0736-5748(99)00084-2Search in Google Scholar

Fischer, R., Schliess, F., and Häussinger, D. (1997). Characterization of the hypo-osmolarity-induced Ca²⁺ response in cultured rat astrocytes. Glia20, 51–58.10.1002/(SICI)1098-1136(199705)20:1<51::AID-GLIA5>3.0.CO;2-8Search in Google Scholar

Flögel, U., Niendorf, T., Serkowa, N., Brand, A., Henke, J., and Leibfritz, D. (1995). Changes in organic solutes, volume, energy state and metabolism associated with osmotic stress in a glial cell line-a multinuclear NMR study. Neurochem. Res.20, 793–802.10.1007/BF00969691Search in Google Scholar

Görg, B., Foster, N., Reinehr, R.M., Bidmon, H.J., Höngen, A., Häussinger, D., and Schliess, F. (2003). Benzodiazepine-induced protein tyrosine nitration in rat astrocytes. Hepatology37, 334–342.10.1053/jhep.2003.50061Search in Google Scholar

Görg, B., Wettstein, M., Metzger, S., Schliess, F., and Häussinger, D. (2005). Lipopolysaccharide-induced tyrosine nitration and inactivation of hepatic glutamine synthetase in the rat. Hepatology41, 1065–1073.10.1002/hep.20662Search in Google Scholar

Görg, B., Bidmon, H.J., Keitel, V., Foster, N., Goerlich, R., Schliess, F., and Häussinger, D. (2006). Inflammatory cytokines induce protein tyrosine nitration in rat astrocytes. Arch. Biochem. Biophys.449, 104–114.10.1016/j.abb.2006.02.012Search in Google Scholar

Groeneweg, M., Quero, J.C., De Bruijn, I., Hartmann, I.J., Essink-Bot, M.L., Hop, W.C., and Schalm, S.W. (1998). Subclinical hepatic encephalopathy impairs daily functioning. Hepatology28, 45–49.10.1002/hep.510280108Search in Google Scholar

Hallbrucker, C., Ritter, M., Lang, F., Gerok, W., and Häussinger, D. (1993). Hydroperoxide metabolism in rat liver. K⁺ channel activation, cell volume changes and eicosanoid formation. Eur. J. Biochem.211, 449–458.Search in Google Scholar

Hansson, E. and Rönnbäck, L. (1995). Astrocytes in glutamate neurotransmission. FASEB J.9, 343–350.10.1096/fasebj.9.5.7534736Search in Google Scholar

Häussinger, D. (1996). The role of cellular hydration in the regulation of cell function. Biochem. J.321, 697–710.10.1042/bj3130697Search in Google Scholar

Häussinger, D. (2006). Low grade cerebral edema and the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology43, 1187–1190.10.1002/hep.21235Search in Google Scholar

Häussinger, D., Laubenberger, J., vom Dahl, S., Ernst, T., Bayer, S., Langer, M., Gerok, W., and Hennig, J. (1994). Proton magnetic resonance spectroscopy studies on human brain myo-inositol in hypoosmolarity and hepatic encephalopathy. Gastroenterology107, 1475–1480.10.1016/0016-5085(94)90552-5Search in Google Scholar

Häussinger, D., Warskulat, U., Fischer, R., Sinning, R., and Schliess, F. (1996). Hepatic encephalopathy. In: Update on Hepatobiliary Desease, S.K. Lam, G. Paumgartner and B. Wang, eds. (Dordrecht, The Netherlands: Kluwer Academic Publishers), pp. 176–178.Search in Google Scholar

Häussinger, D., Kircheis, G., Fischer, R., Schliess, F., and vom Dahl, S. (2000). Hepatic encephalopathy in chronic liver disease: a clinical manifestation of astrocyte swelling and low grade cerebral edema. J. Hepatol.32, 1035–1038.10.1016/S0168-8278(00)80110-5Search in Google Scholar

Hazell, A.S. and Butterworth, R.F. (1999). Hepatic encephalopathy: an update of pathophysiologic mechanisms. Proc. Soc. Exp. Biol. Med.222, 99–112.10.1046/j.1525-1373.1999.d01-120.xSearch in Google Scholar PubMed

Hazell, A.S. and Norenberg, M.D. (1998). Ammonia and manganese increase arginine uptake in cultured astrocytes. Neurochem. Res.23, 869–873.10.1023/A:1022411012512Search in Google Scholar

Hermenegildo, C., Marcaida, G., Montoliu, C., Grisolia, S., Minana, M.D., and Felipo, V. (1996). NMDA receptor antagonists prevent acute ammonia toxicity in mice. Neurochem. Res.21, 1237–1244.10.1007/BF02532401Search in Google Scholar PubMed

Hermenegildo, C., Monfort, P., and Felipo, V. (2000). Activation of N-methyl-d-aspartate receptors in rat brain in vivo following acute ammonia intoxication: characterization by in vivo brain microdialysis. Hepatology31, 709–715.10.1002/hep.510310322Search in Google Scholar PubMed

Hooper, D.C., Scott, G.S., Zborek, A., Mikheeva, T., Kean, R.B., Koprowski, H., and Spitsin, S.V. (2000). Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood-CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis. FASEB J.14, 691–698.10.1096/fasebj.14.5.691Search in Google Scholar PubMed

Hooper, D.C., Kean, R.B., Scott, G.S., Spitsin, S.V., Mikheeva, T., Morimoto, K., Bette, M., Rohrenbeck, A.M., Dietzschold, B., and Weihe, E. (2001). The central nervous system inflammatory response to neurotropic virus infection is peroxynitrite dependent. J. Immunol.167, 3470–3477.10.4049/jimmunol.167.6.3470Search in Google Scholar PubMed

Jayakumar, A.R., Panickar, K.S., and Norenberg, M.D. (2002). Effects on free radical generation by ligands of the peripheral benzodiazepine receptor in cultured neural cells. J. Neurochem.83, 1226–1234.10.1046/j.1471-4159.2002.01261.xSearch in Google Scholar PubMed

Jayakumar, A.R., Rao, K.V., Schousboe, A., and Norenberg, M.D. (2004). Glutamine-induced free radical production in cultured astrocytes. Glia46, 296–301.10.1002/glia.20003Search in Google Scholar PubMed

Jayakumar, A.R., Rao, K.V., Murthy, C., and Norenberg, M.D. (2006). Glutamine in the mechanism of ammonia-induced astrocyte swelling. Neurochem. Int.48, 623–628.10.1016/j.neuint.2005.11.017Search in Google Scholar PubMed

Jones, E.A. (2002). Ammonia, the GABA neurotransmitter system, and hepatic encephalopathy. Metab. Brain Dis.17, 275–281.10.1023/A:1021949616422Search in Google Scholar

Kale, R.A., Gupta, R.K., Saraswat, V.A., Hasan, K.M., Trivedi, R., Mishra, A.M., Ranjan, P., Pandey, C.M., and Narayana, P.A. (2006). Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy. Hepatology43, 698–706.10.1002/hep.21114Search in Google Scholar PubMed

Kean, R.B., Spitsin, S.V., Mikheeva, T., Scott, G.S., and Hooper, D.C. (2000). The peroxynitrite scavenger uric acid prevents inflammatory cell invasion into the central nervous system in experimental allergic encephalomyelitis through maintenance of blood-central nervous system barrier integrity. J. Immunol.165, 6511–6518.10.4049/jimmunol.165.11.6511Search in Google Scholar PubMed

Kimelberg, H.K. (1995). Current concepts of brain edema – review of laboratory investigations. J. Neurosurg.83, 1051–1059.10.3171/jns.1995.83.6.1051Search in Google Scholar PubMed

Kimelberg, H.K. and O'Connor, E.R. (1996). Swelling-induced depolarization of astrocyte membrane potentials. Glia1, 219–242.Search in Google Scholar

Kircheis, G., Wettstein, M., Timmermann, L., Schnitzler, A., and Häussinger, D. (2002). Critical flicker frequency for quantification of low-grade hepatic encephalopathy. Hepatology35, 357–366.10.1053/jhep.2002.30957Search in Google Scholar

Knorpp, T., Robinson, S.R., Crack, P.J., and Dringen, R. (2006). Glutathione peroxidase-1 contributes to the protection of glutamine synthetase in astrocytes during oxidative stress. J. Neural Transm.113, 1145–1155.10.1007/s00702-005-0389-ySearch in Google Scholar

Konopacka, A., Fresko, I., Piaskowski, S., Albrecht, J., and Zielinska, M. (2006). Ammonia affects the activity and expression of soluble and particulate GC in cultured rat astrocytes. Neurochem. Int.58, 553–558.10.1016/j.neuint.2005.12.032Search in Google Scholar

Kosenko, E., Kaminsky, Y., Grau, E., Minana, M.D., Grisolia, S., and Felipo, V. (1995). Nitroarginine, an inhibitor of nitric oxide synthetase, attenuates ammonia toxicity and ammonia-induced alterations in brain metabolism. Neurochem. Res.20, 451–456.10.1007/BF00973101Search in Google Scholar

Kosenko, E., Kaminsky, Y., Lopata, O., Muravyov, N., Kaminsky, A., Hermenegildo, C., and Felipo, V. (1998). Nitroarginine, an inhibitor of nitric oxide synthase, prevents changes in superoxide radical and antioxidant enzymes induced by ammonia intoxication. Metab. Brain Dis.13, 29–41.10.1023/A:1020626928259Search in Google Scholar

Kosenko, E., Kaminsky, Y., Lopata, O., Muravyov, N., and Felipo, V. (1999). Blocking NMDA receptors prevents the oxidative stress induced by acute ammonia intoxication. Free Radic. Biol. Med.26, 1369–1374.10.1016/S0891-5849(98)00339-6Search in Google Scholar

Kosenko, E., Kaminsky, Y., Stavroskaya, I.G., and Felipo, V. (2000). Alteration of mitochondrial calcium homeostasis by ammonia-induced activation of NMDA receptors in rat brain in vivo. Brain Res.880, 139–146.10.1016/S0006-8993(00)02785-2Search in Google Scholar

Kosenko, E., Llansola, M., Montoliu, C., Monfort, P., Rodrigo, R., Hernandez-Viadel, M., Erceg, S., Sanchez-Perez, A.M., and Felipo, V. (2003). Glutamine synthetase activity and glutamine content in brain: modulation by NMDA receptors and nitric oxide. Neurochem. Int.43, 493–499.10.1016/S0197-0186(03)00039-1Search in Google Scholar

Kosenko, E., Montoliu, C., Giordano, G., Kaminsky, Y., Venediktova, N., Buryanov, Y., and Felipo, V. (2004). Acute ammonia intoxication induces an NMDA receptor-mediated increase in poly(ADP-ribose) polymerase level and NAD metabolism in nuclei of rat brain cells. J. Neurochem.89, 1101–1110.10.1111/j.1471-4159.2004.02426.xSearch in Google Scholar PubMed

Lang, F., Busch, G.L., Ritter, M., Völkl, H., Waldegger, S., Gulbins, E., and Häussinger, D. (1998). Functional significance of cell volume regulatory mechanisms. Physiol. Rev.78, 247–306.10.1152/physrev.1998.78.1.247Search in Google Scholar PubMed

Larsen, F.S., Gottstein, J., and Blei, A.T. (2001). Cerebral hyperemia and nitric oxide synthase in rats with ammonia-induced brain edema. J. Hepatol.34, 548–554.10.1016/S0168-8278(00)00069-6Search in Google Scholar

Laubenberger, J., Häussinger, D., Bayer, S., Gufler, H., Hennig, J., and Langer, M. (1997). Proton magnetic resonance spectroscopy of the brain in symptomatic and asymptomatic patients with liver cirrhosis. Gastroenterology112, 1610–1616.10.1016/S0016-5085(97)70043-XSearch in Google Scholar

Martinez, H.A., Bell, K.P., and Norenberg, M.D. (1977). Glutamine synthetase: glial localization in brain. Science195, 1356–1358.10.1126/science.14400Search in Google Scholar PubMed

Master, S., Gottstein, J., and Blei, A.T. (1999). Cerebral blood flow and the development of ammonia-induced brain edema in rats after portacaval anastomosis. Hepatology30, 876–880.10.1002/hep.510300428Search in Google Scholar PubMed

Mayer, M.L., Westbrook, G.L., and Guthrie, P.B. (1984). Voltage-dependent block by Mg²⁺ of NMDA responses in spinal cord neurones. Nature309, 261–263.10.1038/309261a0Search in Google Scholar PubMed

Miese, F., Kircheis, G., Wittsack, H.J., Wenserski, F., Hemker, J., Mödder, U., Häussinger, D., and Cohnen, M. (2006). ¹H-MR spectroscopy, magnetization transfer, and diffusion-weighted imaging in alcoholic and nonalcoholic patients with cirrhosis with hepatic encephalopathy. Am. J. Neuroradiol.27, 1019–1026.Search in Google Scholar

Minguez, B., Garcia-Pagan, J.C., Bosch, J., Turnes, J., Alonso, J., Rovira, A., and Cordoba, J. (2006). Noncirrhotic portal vein thrombosis exhibits neuropsychological and MR changes consistent with minimal hepatic encephalopathy. Hepatology43, 707–714.10.1002/hep.21126Search in Google Scholar PubMed

Morales, M.S., Vaca, L., Hernandez, C.A., and Pasantes, M.H. (1998). Osmotic swelling-induced changes in cytosolic calcium do not affect regulatory volume decrease in rat cultured suspended cerebellar astrocytes. J. Neurochem.71, 2330–2338.Search in Google Scholar

Moran, J., Sabanero, M., Meza, I., and Pasantes, M.H. (1996). Changes of actin cytoskeleton during swelling and regulatory volume decrease in cultured astrocytes. Am. J. Physiol.271, C1901–C1907.10.1152/ajpcell.1996.271.6.C1901Search in Google Scholar PubMed

Morgan, M.Y. (1998). Cerebral magnetic resonance imaging in patients with chronic liver disease. Metab. Brain Dis.13, 273–290.10.1023/A:1020680624084Search in Google Scholar

Murthy, C.R., Rama-Rao, K.V., Bai, G., and Norenberg, M.D. (2001). Ammonia-induced production of free radicals in primary cultures of rat astrocytes. J. Neurosci. Res.66, 282–288.10.1002/jnr.1222Search in Google Scholar PubMed

Musavi, S. and Kakkar, P. (1998). Diazepam induced early oxidative changes at the subcellular level in rat brain. Mol. Cell Biochem.178, 41–46.10.1023/A:1006834706117Search in Google Scholar

Norenberg, M.D. (1994). Astrocyte responses to CNS injury. J. Neuropathol. Exp. Neurol.53, 213–220.10.1097/00005072-199405000-00001Search in Google Scholar

Norenberg, M.D. (1996). Astrocytic-ammonia interactions in hepatic encephalopathy. Semin. Liver Dis.16, 245–253.10.1055/s-2007-1007237Search in Google Scholar

Norenberg, M.D. (2003). Oxidative and nitrosative stress in ammonia neurotoxicity. Hepatology37, 245–248.10.1053/jhep.2003.50087Search in Google Scholar

Norenberg, M.D., Baker, L., Norenberg, L.O., Blicharska, J., Bruce-Gregorios, J.H., and Neary, J.T. (1991). Ammonia-induced astrocyte swelling in primary culture. Neurochem. Res.16, 833–836.10.1007/BF00965694Search in Google Scholar

Norenberg, M.D., Neary, J.T., Bender, A.S., and Dombro, R.S. (1992). Hepatic encephalopathy: a disorder in glial-neuronal communication. Prog. Brain Res.94, 261–269.10.1016/S0079-6123(08)61756-2Search in Google Scholar

Norenberg, M.D., Jayakumar, A.R., and Rama-Rao, K.V. (2004). Oxidative stress in the pathogenesis of hepatic encephalopathy. Metab. Brain. Dis.19, 313–329.10.1023/B:MEBR.0000043978.91675.79Search in Google Scholar

Norenberg, M.D., Jayakumar, A.R., Rama Rao, K.V., and Panickar, K.S. (2006). The peripheral benzodiazepine receptor and neurosteroids in the pathogenesis of hepatic encephalopathy and ammonia neurotoxicity. In: Hepatic Encephalopathy and Nitrogen Metabolism, D. Häussinger, G. Kircheis and F. Schliess, eds. (Dordrecht, The Netherlands: Springer), pp. 143–159.10.1007/1-4020-4456-9_10Search in Google Scholar

O'Connor, E.R. and Kimelberg, H.K. (1993). Role of calcium in astrocyte volume regulation and in the release of ions and amino acids. J. Neurosci.13, 2638–2650.10.1523/JNEUROSCI.13-06-02638.1993Search in Google Scholar

Odeh, M. (1994). Endotoxin and tumor necrosis factor α in the pathogenesis of hepatic encephalopathy. J. Clin. Gastroenterol.19, 146–153.10.1097/00004836-199409000-00016Search in Google Scholar

Ong, J.P., Aggarwal, A., Krieger, D., Easley, K.A., Karafa, M.T., Van, L.F., Arroliga, A.C., and Mullen, K.D. (2003). Correlation between ammonia levels and the severity of hepatic encephalopathy. Am. J. Med.114, 188–193.10.1016/S0002-9343(02)01477-8Search in Google Scholar

Ordaz, B., Tuz, K., Ochoa, L.D., Lezama, R., Pena-Segura, C., and Franco, R. (2004). Osmolytes and mechanisms involved in regulatory volume decrease under conditions of sudden or gradual osmolarity decrease. Neurochem. Res.29, 65–72.10.1023/B:NERE.0000010434.06311.18Search in Google Scholar

Possel, H., Noack, H., Putzke, J., Wolf, G., and Sies, H. (2000). Selective upregulation of inducible nitric oxide synthase (iNOS) by lipopolysaccharide (LPS) and cytokines in microglia: in vitro and in vivo studies. Glia32, 51–59.10.1002/1098-1136(200010)32:1<51::AID-GLIA50>3.0.CO;2-4Search in Google Scholar

Rama-Rao, K.V., Jayakumar, A.R., and Norenberg, D.M. (2003a). Ammonia neurotoxicity: role of the mitochondrial permeability transition. Metab. Brain Dis.18, 113–127.Search in Google Scholar

Rama-Rao, K.V., Jayakumar, A.R., and Norenberg, M.D. (2003b). Induction of the mitochondrial permeability transition in cultured astrocytes by glutamine. Neurochem. Int.43, 517–523.10.1016/S0197-0186(03)00042-1Search in Google Scholar

Rama-Rao, K.V., Jayakumar, A.R., and Norenberg, M.D. (2005). Differential response of glutamine in cultured neurons and astrocytes. J. Neurosci. Res.79, 193–199.10.1002/jnr.20295Search in Google Scholar

Reichenbach, A. (1989). Glia: neuron index: review and hypothesis to account for different values in various mammals. Glia2, 71–77.10.1002/glia.440020202Search in Google Scholar

Reinehr, R.M., Becker, S., Eberle, A., Grether-Beck, S., and Häussinger, D. (2005). Involvement of NADPH oxidase isoforms and SRC family kinases in CD95-dependent hepatocyte apoptosis. J. Biol. Chem.280, 27179–27194.10.1074/jbc.M414361200Search in Google Scholar

Ross, B.D., Jacobson, S., Villamil, F., Korula, J., Kreis, R., Ernst, T., Shonk, T., and Moats, R.A. (1994). Subclinical hepatic encephalopathy: proton MR spectroscopic abnormalities. Radiology193, 457–463.10.1148/radiology.193.2.7972763Search in Google Scholar

Saha, N., Stoll, B., Lang, F., and Häussinger, D. (1992). Effect of anisotonic cell-volume modulation on glutathione-S-conjugate release, t-butylhydroperoxide metabolism and the pentose-phosphate shunt in perfused rat liver. Eur. J. Biochem.209, 437–444.10.1111/j.1432-1033.1992.tb17307.xSearch in Google Scholar

Saha, N., Schreiber, R., vom Dahl, S., Lang, F., Gerok, W., and Häussinger, D. (1993). Endogenous hydroperoxide formation, cell volume and cellular K⁺ balance in perfused rat liver. Biochem. J.296, 701–707.10.1042/bj2960701Search in Google Scholar

Schipke, C.G., Ohlemeyer, C., Matyash, M., Nolte, C., Kettenmann, H., and Kirchhoff, F. (2001). Astrocytes of the mouse neocortex express functional N-methyl-d-aspartate receptors. FASEB J.15, 1270–1272.10.1096/fj.00-0439fjeSearch in Google Scholar

Schliess, F. and Häussinger, D. (2005). The cellular hydration state: role in apoptosis and proliferation. Signal Transduction6, 297–302.10.1002/sita.200400046Search in Google Scholar

Schliess, F., Sinning, R., Fischer, R., Schmalenbach, C., and Häussinger, D. (1996). Calcium-dependent activation of Erk-1 and Erk-2 following hypoosmotic astrocyte-swelling. Biochem. J.319, 167–171.10.1042/bj3200167Search in Google Scholar PubMed PubMed Central

Schliess, F., Heinrich, S., and Häussinger, D. (1998). Hyperosmotic induction of the mitogen-activated protein kinase phosphatase MKP-1 in H4IIE rat hepatoma cells. Arch. Biochem. Biophys.351, 35–40.10.1006/abbi.1997.0517Search in Google Scholar PubMed

Schliess, F., Görg, B., Fischer, R., Desjardins, P., Bidmon, H.J., Herrmann, A., Butterworth, R.F., Zilles, K., and Häussinger, D. (2002). Ammonia induces MK-801-sensitive nitration and phosphorylation of protein tyrosine residues in rat astrocytes. FASEB J.16, 739–741.10.1096/fj.01-0862fjeSearch in Google Scholar PubMed

Schliess, F., Foster, N., Görg, B., Reinehr, R., and Häussinger, D. (2004). Astrocyte swelling increases protein tyrosine nitration in cultured rat astrocytes. Glia47, 21–29.10.1002/glia.20019Search in Google Scholar PubMed

Schliess, F., Görg, B., Reinehr, R.M., Bidmon, H.J., and Häussinger, D. (2006). Osmotic and oxidative stress in hepatic encephalopathy. In: Hepatic Encephalopathy and Nitrogen Metabolism, D. Häussinger, G. Kircheis and F. Schliess, eds. (Dordrecht, The Netherlands: Springer), pp. 20–42.10.1007/1-4020-4456-9_2Search in Google Scholar

Schroeder, P., Klotz, L.O., Buchczyk, D.P., Sadik, C.D., Schewe, T., and Sies, H. (2001). Epicatechin prevents nitration but not oxidation reactions of peroxynitrite. Biochem. Biophys. Res. Commun.285, 782–787.10.1006/bbrc.2001.5210Search in Google Scholar PubMed

Shawcross, D. and Jalan, R. (2005). The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation. Cell Mol. Life Sci.62, 2295–2304.10.1007/s00018-005-5089-0Search in Google Scholar PubMed

Shawcross, D.L., Balata, S., Olde-Damink, S.W., Hayes, P.C., Wardlaw, J., Marshall, I., Deutz, N.E., Williams, R., and Jalan, R. (2004). Low myo-inositol and high glutamine levels in brain are associated with neuropsychological deterioration after induced hyperammonemia. Am. J. Physiol.287, G503–G509.10.1152/ajpgi.00104.2004Search in Google Scholar PubMed

Simard, M. and Nedergaard, M. (2004). The neurobiology of glia in the context of water and ion homeostasis. Neuroscience129, 877–896.10.1016/j.neuroscience.2004.09.053Search in Google Scholar PubMed

Sinning, R., Schliess, F., Kubitz, R., and Häussinger, D. (1997). Osmosignalling in C6 glioma cells. FEBS Lett.400, 163–167.10.1016/S0014-5793(96)01376-2Search in Google Scholar

Siushansian, R., Dixon, S.J., and Wilson, J.X. (1996). Osmotic swelling stimulates ascorbate efflux from cerebral astrocytes. J. Neurochem.66, 1227–1233.10.1046/j.1471-4159.1996.66031227.xSearch in Google Scholar

Song, G., Dhodda, V.K., Blei, A.T., Dempsey, R.J., and Rao, V.L.R. (2002). GeneChip analysis shows altered mRNA expression of transcripts of neurotransmitter and signal transduction pathways in the cerebral cortex of portacaval shunted rats. J. Neurosci. Res.68, 730–737.10.1002/jnr.10268Search in Google Scholar

Stewart, V.C., Sharpe, M.A., Clark, J.B., and Heales, S.J. (2000). Astrocyte-derived nitric oxide causes both reversible and irreversible damage to the neuronal mitochondrial respiratory chain. J. Neurochem.75, 694–700.10.1046/j.1471-4159.2000.0750694.xSearch in Google Scholar

Sykova, E. (2005). Glia and volume transmission during physiological and pathological states. J. Neural. Transm.112, 137–147.10.1007/s00702-004-0120-4Search in Google Scholar

Sykova, E., Vargova, L., Prokopova, S., and Simonova, Z. (1999). Glial swelling and astrogliosis produce diffusion barriers in the rat spinal cord. Glia25, 56–70.10.1002/(SICI)1098-1136(19990101)25:1<56::AID-GLIA6>3.0.CO;2-4Search in Google Scholar

Takahashi, H., Koehler, R.C., Brusilow, S.W., and Traystman, R.J. (1990). Glutamine synthetase inhibition prevents cerebral oedema during hyperammonemia. Acta Neurochir. (Vienna) (Suppl.) 51, 346–347.10.1007/978-3-7091-9115-6_117Search in Google Scholar

Timmermann, L., Gross, J., Kircheis, G., Häussinger, D., and Schnitzler, A. (2002). Cortical origin of mini-asterixis in hepatic encephalopathy. Neurology58, 295–298.10.1212/WNL.58.2.295Search in Google Scholar

Timmermann, L., Gross, J., Butz, M., Kircheis, G., Häussinger, D., and Schnitzler, A. (2003). Mini-asterixis in hepatic encephalopathy induced by pathologic thalamo-motor-cortical coupling. Neurology61, 689–692.10.1212/01.WNL.0000078816.05164.B1Search in Google Scholar

Vaquero, J., Chung, C., Cahill, M.E., and Blei, A.T. (2003). Pathogenesis of hepatic encephalopathy in acute liver failure. Semin. Liver Dis.23, 259–269.Search in Google Scholar

Vaquero, J., Chung, C., and Blei, A.T. (2004). Cerebral blood flow in acute liver failure: a finding in search of a mechanism. Metab. Brain Dis.19, 177–194.10.1023/B:MEBR.0000043968.04313.e7Search in Google Scholar

Vogels, B.A., Maas, M.A., Daalhuisen, J., Quack, G., and Chamuleau, R.A. (1997). Memantine, a noncompetitive NMDA receptor antagonist improves hyperammonemia-induced encephalopathy and acute hepatic encephalopathy in rats. Hepatology25, 820–827.10.1002/hep.510250406Search in Google Scholar

Warren, K.S. and Schencker, S. (1964). Effect of an inhibitor of glutamine synthesis (methionine sulfoximine) on ammonia toxicity and metabolism. J. Lab. Clin. Med.64, 442–449.Search in Google Scholar

Warskulat, U., Kreuels, S., Müller, H.W., and Häussinger, D. (2001). Identification of osmosensitive and ammonia-regulated genes in rat astrocytes by northern blotting and differential display reverse transcriptase-polymerase chain reaction. J. Hepatol.35, 358–366.10.1016/S0168-8278(01)00149-0Search in Google Scholar

Warskulat, U., Görg, B., Bidmon, H.J., Müller, H.W., Schliess, F., and Häussinger, D. (2002). Ammonia-induced heme oxygenase 1 expression in cultured rat astrocytes and in rat brain in vivo. Glia40, 324–336.10.1002/glia.10128Search in Google Scholar

Wein, C., Koch, H., Popp, B., Oehler, G., and Schauder, P. (2004). Minimal hepatic encephalopathy impairs fitness to drive. Hepatology39, 739–745.10.1002/hep.20095Search in Google Scholar

Willard-Mack, C.L., Koehler, R.C., Hirata, T., Cork, L.C., Takahashi, H., Traystman, R.J., and Brusilow, S.W. (1996). Inhibition of glutamine synthetase reduces ammonia-induced astrocyte swelling in rat. Neuroscience71, 589–599.10.1016/0306-4522(95)00462-9Search in Google Scholar

Xu, D., Wang, L., Olson, J.E., and Lu, L. (2001). Asymmetrical response of p38 kinase activation to volume changes in primary rat astrocytes. Exp. Biol. Med.226, 927–933.10.1177/153537020122601008Search in Google Scholar

Yang, T.X., Zhang, A.H., Honeggar, M., Kohan, D.E., Mizel, D., Sanders, K., Hoidal, J.R., Briggs, J.P., and Schnermann, J.B. (2005). Hypertonic induction of COX-2 in collecting duct cells by reactive oxygen species of mitochondrial origin. J. Biol. Chem.280, 34966–34973.10.1074/jbc.M502430200Search in Google Scholar

Zielinska, M., Law, R.O., and Albrecht, J. (2003). Excitotoxic mechanism of cell swelling in rat cerebral cortical slices treated acutely with ammonia. Neurochem. Int.43, 299–303.10.1016/S0197-0186(03)00015-9Search in Google Scholar