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Cerebral Blood Flow in Acute Liver Failure: A Finding in Search of a Mechanism

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Abstract

In the last few years, several abnormalities of cerebral blood flow (CBF), namely loss of cerebral autoregulation, altered reactivity to carbon dioxide, and development of cerebral hyperemia, have been described in patients as well as experimental models of acute liver failure (ALF) and/or hyperammonemia. The development of cerebral hyperemia seems particularly relevant to the pathogenesis of brain edema in ALF. In addition to the potential increase of brain blood volume causing a rise in intracranial pressure, an increase of CBF could facilitate the movement of water across the blood brain barrier in an osmotically altered brain. Because maneuvers that abrogate the rise of CBF have been shown to prevent or ameliorate brain edema in ALF/hyperammonemia, elucidation of the mechanism by which the rise of CBF occurs is important. In the rat after portacaval anastomosis receiving an ammonia infusion, the signal resulting in cerebral hyperemia arises within the brain once maximal glutamine accumulation has occurred in astrocytes. Several mediators potentially involved in the development of cerebral hyperemia in ALF are examined in this review, but further work is needed to assess the role, if any, of each of them.

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REFERENCES

  • Aggarwal, S., Kramer, D., Yonas, H., Obrist, W., Kang, Y., Martin, M., and Policare, R. (1994). Cerebral hemodynamic and metabolic changes in fulminant hepatic failure: A retrospective study. Hepatology 19:80–87.

    Google Scholar 

  • Aggarwal, S., Yonas, H., Kang, Y., Martin, M., Kramer, D., Obrist, W.D., and Darby, J. (1991). Relationship of cerebral blood flow and cerebral swelling to outcome in patients with acute fulminant hepatic failure. ] Transpl. Proc. 23:19781979.

    Google Scholar 

  • Alkayed, N.J., Birks, E.K., Hudetz, A.G., Roman, R.J., Henderson, L., and Harder, D.R. (1996). Inhibition of brain P-450 arachidonic acid epoxygenase decreases baseline cerebral blood flow. Am.J.Physiol. 271:H1541–H1546.

    PubMed  Google Scholar 

  • Anda, T., Yamashita, H., Khalid, H., Tsutsumi, K., Fujita, H., Tokunaga, Y., and Shibata, S. (1997). Effect of tumor necrosis factor-alpha on the permeability of bovine brain microvessel endothelial cell monolayers. Neurol. Res. 19:369–376.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Balata, S., Damink, S.W., Ferguson, K., Marshall, I., Hayes, P.C., Deutz, N.E., Williams, R., Wardlaw, J., and Jalan, R. (2003). Induced hyperammonemia alters neuropsychology, brain MR spectroscopy and magnetization transfer in cirrhosis. Hepatology 37:931–939.

    PubMed  Google Scholar 

  • Banks, W.A., Kastin, A.J., and Gutierrez, E.G. (1993). Interleukin-1 alpha in blood has direct access to cortical brain cells. Neurosci. Lett. 163:41–44.

    PubMed  Google Scholar 

  • Banks, W.A., Kastin, A.J., and Gutierrez, E.G. (1994). Penetration of interleukin-6 across the murine blood-brain barrier. Neurosci. Lett. 179:53–56.

    PubMed  Google Scholar 

  • Bates, T.E., Williams, S.R., Kauppinen, R.A., and Gadian, D.G. (1989). Observation of cerebral metabolites in an animal model of acute liver failure in vivo: A 1H and 31P nuclear magnetic resonance study. J. Neurochem. 53:102–110.

    PubMed  Google Scholar 

  • Bender, A.S., Rivera, I.V., and Norenberg, M.D. (1992). Tumor necrosis factor-alpha induces astrocyte swelling [Abstract]. Trans. Am. Neurochem. 23:113.

    Google Scholar 

  • Berk, P.D., and Popper, H. (1978). Fulminant hepatic failure. Am. J. Gastroenterol. 69:349–400.

    PubMed  Google Scholar 

  • Bickel, U., Grave, B., Kang, Y.S., del Rey, A., and Voigt, K. (1998). No increase in blood-brain barrier permeability after intraperitoneal injection of endotoxin in the rat. J. Neuroimmunol. 85:131–136.

    PubMed  Google Scholar 

  • Bihari, D., Gimson, A.E., Lindridge, J., and Williams, R. (1985a). Lactic acidosis in fulminant hepatic failure. Some aspects of pathogenesis and prognosis. J. Hepatol. 1:405–416.

    PubMed  Google Scholar 

  • Bihari, D., Gimson, A.E., Waterson, M., and Williams, R. (1985b). Tissue hypoxia during fulminant hepatic failure. Crit. Care Med. 13:1034–1039.

    PubMed  Google Scholar 

  • Blei, A.T. (2001). Pathophysiology of brain edema in fulminant hepatic failure, revisited. Metab. Brain Dis. 16:85–94.

    PubMed  Google Scholar 

  • Blei, A.T., and Larsen, F.S. (1999). Pathophysiology of cerebral edema in fulminant hepatic failure. J. Hepatol. 31:771–776.

    PubMed  Google Scholar 

  • Bonmann, E., Suschek, C., Spranger, M., and Kolb-Bachofen, V. (1997). The dominant role of exogenous or en-dogenous interleukin-1 beta on expression and activity of inducible nitric oxide synthase in rat microvascular brain endothelial cells. Neurosci. Lett. 230:109–112.

    PubMed  Google Scholar 

  • Bosman, D.K., Deutz, N.E., De Graaf, A.A., vd Hulst, R.W., Van Eijk, H.M., Bovee, W.M., Maas, M.A., Jorning, G.G., and Chamuleau, R.A. (1990). Changes in brain metabolism during hyperammonemia and acute liver failure: Results of a comparative 1H-NMR spectroscopy and biochemical investigation. Hepatology 12:281–290.

    PubMed  Google Scholar 

  • Bosman, D.K., Deutz, N.E., Maas, M.A., van Eijk, H.M., Smit, J.J., de Haan, J.G., and Chamuleau, R.A. (1992). Amino acid release from cerebral cortex in experimental acute liver failure, studied by in vivo cerebral cortex microdialysis. J. Neurochem. 59:591–599.

    PubMed  Google Scholar 

  • Bowie, R.A., O'Connor, P.J., and Mahajan, R.P. (2003). Cerebrovascular reactivity to carbon dioxide in sepsis syndrome. Anaesthesia 58:261–265.

    PubMed  Google Scholar 

  • Bowton, D.L., Bertels, N.H., Prough, D.S., and Stump, D.A. (1989). Cerebral blood flow is reduced in patients with sepsis syndrome. Crit. Care Med. 17:399–403.

    PubMed  Google Scholar 

  • Castilho, R.F., Kowaltowski, A.J., Meinicke, A.R., Bechara, E.J., and Vercesi, A.E. (1995). Permeabilization of the inner mitochondrial membrane by Ca 2 +ions is stimulated by t-butyl hydroperoxide and mediated by reactive oxygen species generated by mitochondria. Free Radic. Biol. Med. 18:479–486.

    PubMed  Google Scholar 

  • Chan, H., and Butterworth, R.F. (1999). Evidence for an astrocytic glutamate transporter deficit in hepatic encephalopathy. Neurochem. Res. 24:1397–1401.

    PubMed  Google Scholar 

  • Chan, H., Hazell, A.S., Desjardins, P., and Butterworth, R.F. (2000). Effects of ammonia on glutamate transporter (GLAST) protein and mRNA in cultured rat cortical astrocytes. Neurochem. Int. 37:243–248.

    PubMed  Google Scholar 

  • Chatauret, N., Rose, C., Therrien, G., and Butterworth, R.F. (2001). Mild hypothermia prevents cerebral edema and CSF lactate accumulation in acute liver failure. Metab. Brain Dis. 16:95–102.

    PubMed  Google Scholar 

  • Chen, Y.L., Wolin, M.S., and Messina, E.J. (1996). Evidence for cGMP mediation of skeletal muscle arteriolar dilation to lactate. J. Appl. Physiol. 81:349–354.

    PubMed  Google Scholar 

  • Chung, C., Gottstein, J., and Blei, A.T. (2001). Indomethacin prevents the development of experimental ammonia-induced brain edema in rats after portacaval anastomosis. Hepatology 34:249–254.

    PubMed  Google Scholar 

  • Chung, C., Vaquero, J., Gottstein, J., and Blei, A.T. (2003). Vasopressin accelerates experimental ammonia-induced brain edema in rats after portacaval anastomosis. J. Hepatol. 39:193–199.

    PubMed  Google Scholar 

  • Clemmesen, J.O., Hansen, B.A., and Larsen, F.S. (1997). Indomethacin normalizes intracranial pressure in acute liver failure: A twenty-three-year-old woman treated with indomethacin. Hepatology 26:1423–1425.

    PubMed  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 (1)H-magnetic resonance abnormalities after liver transplantation. J. Hepatol. 35:598–604.

    PubMed  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. Gastroenterology 116:686–693.

    PubMed  Google Scholar 

  • Cordoba, J., Gottstein, J., and Blei, A.T. (1996). Glutamine, myo-inositol, and organic brain osmolytes after portocaval anastomosis in the rat: Implications for ammonia-induced brain edema. Hepatology 24:919–923.

    Article  PubMed  Google Scholar 

  • Desjardins, P., Bandeira, P., Rao, V.L., and Butterworth, R.F. (1999). Portacaval anastomosis causes selective alter-ations of peripheral-type benzodiazepine receptor expression in rat brain and peripheral tissues. Neurochem.Int. 35:293–299.

    PubMed  Google Scholar 

  • Desjardins, P., and Butterworth, R.F. (2002). The "peripheral-type" benzodiazepine (omega 3) receptor in hyper-ammonemic disorders. Neurochem. Int. 41:109–114.

    PubMed  Google Scholar 

  • de Vries, H.E., Blom-Roosemalen, M.C., van Oosten, M., de Boer, A.G., van Berkel, T.J., Breimer, D.D., and Kuiper, J. (1996). The influence of cytokines on the integrity of the blood-brain barrier in vitro. J.Neuroimmunol. 64:37–43.

    PubMed  Google Scholar 

  • Durham, S., Yonas, H., Aggarwal, S., Darby, J., and Kramer, D. (1995). Regional cerebral blood flow and CO2 reactivity in fulminant hepatic failure. J. Cereb. Blood Flow Metab. 15:329–335.

    PubMed  Google Scholar 

  • Fernandez, M., and Bonkovsky, H.L. (1999). Increased heme oxygenase-1 gene expression in liver cells and splanchnic organs from portal hypertensive rats. Hepatology 29:1672–1679.

    PubMed  Google Scholar 

  • Fernandez, M., Lambrecht, R.W., and Bonkovsky, H.L. (2001). Increased heme oxygenase activity in splanchnic organs from portal hypertensive rats: Role in modulating mesenteric vascular reactivity. J. Hepatol. 34:812–817.

    PubMed  Google Scholar 

  • Gebremedhin, D., Ma, Y.H., Falck, J.R., Roman, R.J., VanRollins, M., and Harder, D.R. (1992). Mechanism of action of cerebral epoxyeicosatrienoic acids on cerebral arterial smooth muscle. Am. J. Physiol. 263:H519–H525.

    PubMed  Google Scholar 

  • Gutierrez, E.G., Banks, W.A., and Kastin, A.J. (1993). Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. J. Neuroimmunol. 47:169–176.

    PubMed  Google Scholar 

  • Harder, D.R., Zhang, C., and Gebremedhin, D. (2002). Astrocytes function in matching blood flow to metabolic activity. News Physiol. Sci. 17:27–31.

    PubMed  Google Scholar 

  • Hashimoto, M., Ishikawa, Y., Yokota, S., Goto, F., Bando, T., Sakakibara, Y., and Iriki, M. (1991). Action site of circulating interleukin-1 on the rabbit brain. Brain Res. 540:217–223.

    PubMed  Google Scholar 

  • Haussinger, 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 hypo-osmolarity and hepatic encephalopathy. Gastroenterology 107:1475–1480.

    PubMed  Google Scholar 

  • Hazell, A.S., and Norenberg, M.D. (1998). Ammonia and manganese increase arginine uptake in cultured astro-cytes. Neurochem. Res. 23:869–873.

    Article  PubMed  Google Scholar 

  • 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. Hepatology 31:709–715.

    PubMed  Google Scholar 

  • Hirata, T., Kawaguchi, T., Brusilow, S.W., Traystman, R.J., and Koehler, R.C. (1999). Preserved hypocapnic pial arteriolar constriction during hyperammonemia by glutamine synthetase inhibition. Am. J. Physiol.

  • Hirata, T., Koehler, R.C., Kawaguchi, T., Brusilow, S.W., and Traystman, R.J. (1996). Impaired pial arteriolar reactivity to hypercapnia during hyperammonemia depends on glutamine synthesis. Stroke 27:729–736.

    PubMed  Google Scholar 

  • Hortelano, S., Dallaporta, B., Zamzami, N., Hirsch, T., Susin, S.A., Marzo, I., Bosca, L., and Kroemer, G. (1997). Nitric oxide induces apoptosis via triggering mitochondrial permeability transition. FEBS Lett. 410:373–377.

    PubMed  Google Scholar 

  • Hotchkiss, R.S., and Karl, I.E. (1992). Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis. JAMA 267:1503–1510.

    PubMed  Google Scholar 

  • Jalan, R., Damink, S.W., Deutz, N.E., Lee, A., and Hayes, P.C. (1999). Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure. Lancet 354:1164–1168.

    PubMed  Google Scholar 

  • Jalan, R., Damink, S.W., Hayes, P.C., Deutz, N.E., and Lee, A. (2001c). A rise in cerebral blood flow precedes intracranial hypertension in patients with acute liver failure (ALF). Hepatology 34:298A.

    Google Scholar 

  • Jalan, R., Olde Damink, S.W., Deutz, N.E., Hayes, P.C., and Lee, A. (2001a). Restoration of cerebral blood flow autoregulation and reactivity to carbon dioxide in acute liver failure by moderate hypothermia. Hepatology 34:50–54.

    PubMed  Google Scholar 

  • Jalan, R., and Williams, R. (2001b). The inflammatory basis of intracranial hypertension in acute liver failure. J. Hepatol. 34:940–942.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Keane, H.M., Sheron, N., Goka, J., Hughes, R.D., and Williams, R. (1996). Plasma inhibitory activity against tumour necrosis factor in fulminant hepatic failure. Clin. Sci. (Lond.) 90:77–80.

    Google Scholar 

  • Knot, H.J., Zimmermann, P.A., and Nelson, M.T. (1996). Extracellular K( +)-induced hyperpolarizations and dilatations of rat coronary and cerebral arteries involve inward rectifier K( +) channels. J. Physiol. 492(Pt. 2):419–430.

    PubMed  Google Scholar 

  • Kontos, H.A., Wei, E.P., Povlishock, J.T., and Christman, C.W. (1984). Oxygen radicals mediate the cerebral arteriolar dilation from arachidonate and bradykinin in cats. Circ. Res. 55:295–303.

    PubMed  Google Scholar 

  • Kuschinsky, W., and Poulson, O.B. (1992) Capillary circulation in the brain. Cerebrovasc. Brain Metab. Rev. 4:261–286.

    PubMed  Google Scholar 

  • Kuschinsky, W., Wahl, M., Bosse, O., and Thurau, K. (1972). Perivascular potassium and pH as determinants of local pial arterial diameter in cats. A microapplication study. Circ. Res. 31:240–247.

    PubMed  Google Scholar 

  • Lacroix, S., and Rivest, S. (1998). Effect of acute systemic inflammatory response and cytokines on the transcrip-tion of the genes encoding cyclooxygenase enzymes (COX-1 and COX-2) in the rat brain. J. Neurochem. 70:452–466.

    PubMed  Google Scholar 

  • Larsen, F.S. (2002a). Cerebral blood flow in hyperammonemia: Heterogeneity and starling forces in capillaries. Metab. Brain Dis. 17:229–235.

    PubMed  Google Scholar 

  • Larsen, F.S., Adel Hansen, B., Pott, F., Ejlersen, E., Secher, N.H., Paulson, O.B., and Knudsen, G.M. (1996a). Dissociated cerebral vasoparalysis in acute liver failure. A hypothesis of gradual cerebral hyperaemia. J. Hepatol. 25:145–151.

    PubMed  Google Scholar 

  • Larsen, F.S., Ejlersen, E., Clemmesen, J.O., Kirkegaard, P., and Hansen, B.A. (1996b). Preservation of cerebral oxidative metabolism in fulminant hepatic failure: An autoregulation study. Liver Transpl. Surg. 2:348–353.

    PubMed  Google Scholar 

  • Larsen, F.S., Ejlersen, E., Hansen, B.A., Knudsen, G.M., Tygstrup, N., and Secher, N.H. (1995). Functional loss of cerebral blood flow autoregulation in patients with fulminant hepatic failure. J. Hepatol. 23:212–217.

    PubMed  Google Scholar 

  • Larsen, F.S., Gottstein, J., and Blei, A.T. (2001a). Cerebral hyperemia and nitric oxide synthase in rats with ammonia-induced brain edema. J. Hepatol. 34:548–554.

    PubMed  Google Scholar 

  • Larsen, F.S., Knudsen, G.M., Paulson, O.B., and Vilstrup, H. (1994). Cerebral blood flow autoregulation is absent in rats with thioacetamide-induced hepatic failure. J. Hepatol. 21:491–495.

    PubMed  Google Scholar 

  • Larsen, F.S., Moller, K., and Strauss, G. (2001b). Specific cerebral efflux of potassium in patients with fulminant hepatic failure [Abstract]. Liver Transpl. 7:C22.

    Google Scholar 

  • Larsen, F.S., and Wendon, J. (2002b). Brain edema in liver failure: Basic physiologic principles and management. Liver Transpl. 8:983–989.

    PubMed  Google Scholar 

  • Licinio, J., and Wong, M.L. (1997). Pathways and mechanisms for cytokine signaling of the central nervous system. J. Clin. Invest. 100:2941–2947.

    PubMed  Google Scholar 

  • Magistretti, P.J., Pellerin, L., Rothman, D.L., and Shulman, R.G. (1999). Energy on demand. Science 283:496–497.

    PubMed  Google Scholar 

  • 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. Hepatology 30:876–880.

    PubMed  Google Scholar 

  • Matta, B.F., and Stow, P.J. (1996). Sepsis-induced vasoparalysis does not involve the cerebral vasculature: Indirect evidence from autoregulation and carbon dioxide reactivity studies. Br. J. Anaesth. 76:790–794.

    PubMed  Google Scholar 

  • Michalak, A., Rose, C., Butterworth, J., and Butterworth, R.F. (1996). Neuroactive amino acids and glutamate (NMDA) receptors in frontal cortex of rats with experimental acute liver failure. Hepatology 24:908–913.

    Google Scholar 

  • Moller, K., Strauss, G.I., Qvist, J., Fonsmark, L., Knudsen, G.M., Larsen, F.S., Krabbe, K.S., Skinhoj, P., and Pedersen, B.K. (2002). Cerebral blood flow and oxidative metabolism during human endotoxemia. J. Cereb. Blood. Flow Metab. 22:1262–1270.

    PubMed  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.

    PubMed  Google Scholar 

  • Muto, Y., Nouri-Aria, K.T., Meager, A., Alexander, G.J., Eddleston, A.L., and Williams, R. (1988). Enhanced tumour necrosis factor and interleukin-1 in fulminant hepatic failure. Lancet 2:72–74.

    PubMed  Google Scholar 

  • Niwa, K., Araki, E., Morham, S.G., Ross, M.E., and Iadecola, C. (2000). Cyclooxygenase-2 contributes to functional hyperemia in whisker-barrel cortex. J. Neurosci. 20:763–770.

    PubMed  Google Scholar 

  • Niwa, K., Haensel, C., Ross, M.E., and Iadecola, C. (2001). Cyclooxygenase-1 participates in selected vasodilator responses of the cerebral circulation. Circ. Res. 88:600–608.

    PubMed  Google Scholar 

  • Osburg, B., Peiser, C., Domling, D., Schomburg, L., Ko, Y.T., Voigt, K., and Bickel, U. (2002). Effect of endotoxin on expression of TNF receptors and transport of TNF-alpha at the blood-brain barrier of the rat. Am.J.Physiol. Endocrinol. Metab. 283:E899–E908.

    PubMed  Google Scholar 

  • Parfenova, H., Levine, V., Gunther, W.M., Pourcyrous, M., and Leffler, C.W. (2002). COX-1 and COX-2 con-tributions to basal and IL-1 beta-stimulated prostanoid synthesis in human neonatal cerebral microvascular endothelial cells. Pediatr. Res. 52:342–348.

    PubMed  Google Scholar 

  • Parfenova, H., Parfenov, V.N., Shlopov, B.V., Levine, V., Falkos, S., Pourcyrous, M., and Leffler, C.W. (2001). Dynamics of nuclear localization sites for COX-2 in vascular endothelial cells. Am. J. Physiol. Cell Physiol. 281:C166–C178.

    PubMed  Google Scholar 

  • Paulson, O.B., and Newman, E.A. (1987). Does the release of potassium from astrocyte endfeet regulate cerebral blood flow? Science 237:896–898.

    PubMed  Google Scholar 

  • Pellerin, L. (2003). Lactate as a pivotal element in neuron-glia metabolic cooperation. Neurochem. Int. 43:331–338.

    PubMed  Google Scholar 

  • Pollard, V., Prough, D.S., Deyo, D.J., Conroy, B., Uchida, T., Daye, A., Traber, L.D., and Traber, D.L. (1997). Cerebral blood flow during experimental endotoxemia in volunteers. Crit. Care Med. 25:1700–1706.

    PubMed  Google Scholar 

  • Quan, N., Whiteside, M., and Herkenham, M. (1998). Cyclooxygenase 2 mRNA expression in rat brain after peripheral injection of lipopolysaccharide. Brain Res. 802:189–197.

    PubMed  Google Scholar 

  • Rama Rao, K.V., Bai, G., Jayakumar, A.R., and Norenberg, M.D. (2001). Role of the peripheral benzodiazepine receptor and neurosteroids in the induction of the mitochondrial permeability transition in cultured astrocytes. J. Neurochem. 78:25.

    Google Scholar 

  • Rama Rao, K.V., Jayakumar, A.R., and Norenberg, M.D. (2003). Induction of the mitochondrial permeability transition in cultured astrocytes by glutamine. Neurochem. Int. 43:517–523.

    PubMed  Google Scholar 

  • Rao, V.L., Audet, R.M., and Butterworth, R.F. (1995). Increased nitric oxide synthase activities and L-[3H]arginine uptake in brain following portacaval anastomosis. J. Neurochem. 65:677–678.

    PubMed  Google Scholar 

  • Rao, V.L., Audet, R.M., and Butterworth, R.F. (1997). Increased neuronal nitric oxide synthase expression in brain following portacaval anastomosis. Brain Res. 765:169–172.

    Article  PubMed  Google Scholar 

  • Rolando, N., Harvey, F., Brahm, J., Philpott-Howard, J., Alexander, G., Gimson, A., Casewell, M., Fagan, E., and Williams, R. (1990). Prospective study of bacterial infection in acute liver failure: An analysis of fifty patients. Hepatology 11:49–53.

    PubMed  Google Scholar 

  • Rolando, N., Wade, J., Davalos, M., Wendon, J., Philpott-Howard, J., and Williams, R. (2000). The systemic inflammatory response syndrome in acute liver failure. Hepatology 32:734–739.

    PubMed  Google Scholar 

  • Rose, C., Michalak, A., Pannunzio, M., Chatauret, N., Rambaldi, A., and Butterworth, R.F. (2000). Mild hypother-mia delays the onset of coma and prevents brain edema and extracellular brain glutamate accumulation in rats with acute liver failure. Hepatology 31:872–877.

    PubMed  Google Scholar 

  • Rosenblum, W.I. (1987). Hydroxyl radical mediates the endothelium-dependent relaxation produced by bradykinin in mouse cerebral arterioles. Circ. Res. 61:601–603.

    PubMed  Google Scholar 

  • Ryter, S.W., Otterbein, L.E., Morse, D., and Choi, A.M. (2002). Heme oxygenase/carbon monoxide signaling pathways: Regulation and functional significance. Mol. Cell. Biochem. 234–235:249–263.

    Google Scholar 

  • Saija, A., Princi, P., Lanza, M., Scalese, M., Aramnejad, E., and De Sarro, A. (1995). Systemic cytokine admin-istration can affect blood-brain barrier permeability in the rat. Life Sci. 56:775–784.

    PubMed  Google Scholar 

  • Salvemini, D., Misko, T.P., Masferrer, J.L., Seibert, K., Currie, M.G., and Needleman, P. (1993). Nitric oxide activates cyclooxygenase enzymes. Proc. Natl. Acad. Sci. U. S. A. 90:7240–7244.

    PubMed  Google Scholar 

  • Schliess, F., Gorg, B., Fischer, R., Desjardins, P., Bidmon, H.J., Herrmann, A., Butterworth, R.F., Zilles, K., and Haussinger, D. (2002). Ammonia induces MK-801-sensitive nitration and phosphorylation of protein tyrosine residues in rat astrocytes. FAS EB J. 16:739–741.

    Google Scholar 

  • Sekiyama, K.D., Yoshiba, M., and Thomson, A.W. (1994). Circulating proinflammatory cytokines (IL-1beta, TNF-alpha, and IL-6) and IL-1 receptor antagonist (IL-1Ra) in fulminant hepatic failure and acute hepatitis. Clin. Exp. Immunol. 98:71–77.

    PubMed  Google Scholar 

  • Song, G., Dhodda, V.K., Blei, A.T., Dempsey, R.J., and Rao, V.L. (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.

    PubMed  Google Scholar 

  • Sugimoto, H., Koehler, R.C., Wilson, D.A., Brusilow, S.W., and Traystman, R.J. (1997). Methionine sulfox-imine, a glutamine synthetase inhibitor, attenuates increased extracellular potassium activity during acute hyperammonemia. J. Cereb. Blood Flow Metab. 17:44–49.

    PubMed  Google Scholar 

  • 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 15:449–453.

    PubMed  Google Scholar 

  • Takada, Y., Ishiguro, S., Fukunaga, K., Gu, M., Taniguchi, H., Seino, K.I., Yuzawa, K., Otsuka, M., Todoroki, T., and Fukao, K. (2001). Increased intracranial pressure in a porcine model of fulminant hepatic failure using amatoxin and endotoxin. J. Hepatol. 34:825–831.

    PubMed  Google Scholar 

  • Takahashi, H., Koehler, R.C., Hirata, T., Brusilow, S.W., and Traystman, R.J. (1992). Restoration of cerebrovascular CO2 responsivity by glutamine synthesis inhibition in hyperammonemic rats. Circ. Res. 71:1220–1230.

    PubMed  Google Scholar 

  • Taylor-Robinson, S.D., Sargentoni, J., Marcus, C.D., Morgan, M.Y., and Bryant, D.J. (1994). Regional variations in cerebral proton spectroscopy in patients with chronic hepatic encephalopathy. Metab. Brain Dis. 9:347–359.

    PubMed  Google Scholar 

  • Tofteng, F., Jorgensen, L., Hansen, B.A., Ott, P., Kondrup, J., and Larsen, F.S. (2002a). Cerebral microdialysis in patients with fulminant hepatic failure. Hepatology 36:1333–1340.

    PubMed  Google Scholar 

  • Tofteng, F., and Larsen, F.S. (2002b). Monitoring extracellular concentrations of lactate, glutamate, and glycerol by in vivo microdialysis in the brain during liver transplantation in acute liver failure. Liver Transpl. 8:302–305.

    PubMed  Google Scholar 

  • Tominaga, S., Watanabe, A., and Tsuji, T. (1991). Synergistic effect of bile acid, endotoxin, and ammonia on brain edema. Metab. Brain Dis. 6:93–105.

    PubMed  Google Scholar 

  • Traber, P., DalCanto, 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.

    PubMed  Google Scholar 

  • Traber, P.G., Ganger, D.R., and Blei, A.T. (1986). Brain edema in rabbits with galactosamine-induced fulminant hepatitis. Regional differences and effects on intracranial pressure. Gastroenterology 91:1347–1356.

    PubMed  Google Scholar 

  • Unterberg, A., Wahl, M., and Baethmann, A. (1988). Effects of free radicals on permeability and vasomotor response of cerebral vessels. Acta Neuropathol. (Berl.) 76:238–244.

    Google Scholar 

  • Van Dam, A.M., De Vries, H.E., Kuiper, J., Zijlstra, F.J., De Boer, A.G., Tilders, F.J., and Berkenbosch, F. (1996). Interleukin-1 receptors on rat brain endothelial cells: A role in neuroimmune interaction? FAS EB J. 10:351–356.

    Google Scholar 

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

    PubMed  Google Scholar 

  • Vaquero, J., Polson, J., Chung, C., Helenowski, I., Schiodt, F.V., Reisch, J., Lee, W.M., and Blei, A.T. (2003b). Infection and the progression of hepatic encephalopathy in acute liver failure. Gastroenterology 125:755–764.

    PubMed  Google Scholar 

  • Venkatasubramanian, P.N., Tom, B., Blei, A.T., and Wyrwicz, A.M. (2001). Monitoring of brain water by chemical shift imaging during ammonia-induced brain swelling in rats after portacaval anastomosis. Artif. Organs 25:551–557.

    PubMed  Google Scholar 

  • Verma, A., Nye, J.S., and Snyder, S.H. (1987). Porphyrins are endogenous ligands for the mitochondrial (peripheral-type) benzodiazepine receptor. Proc. Natl. Acad. Sci. U. S. A. 84:2256–2260.

    PubMed  Google Scholar 

  • Warskulat, U., Gorg, B., Bidmon, H.J., Muller, H.W., Schliess, F., and Haussinger, D. (2002). Ammonia-induced heme oxygenase-1 expression in cultured rat astrocytes and rat brain in vivo. Glia 40:324–336.

    PubMed  Google Scholar 

  • Wei, E.P., Christman, C.W., Kontos, H.A., and Povlishock, J.T. (1985). Effects of oxygen radicals on cerebral arterioles. Am.J.Physiol. 248:H157–H162.

    PubMed  Google Scholar 

  • Wei, E.P., Kontos, H.A., and Beckman, J.S. (1996). Mechanisms of cerebral vasodilation by superoxide, hydrogen peroxide, and peroxynitrite. Am. J. Physiol. 271:H1262–H1266.

    PubMed  Google Scholar 

  • Wei, E.P., Kontos, H.A., and Beckman, J.S. (1998). Antioxidants inhibit ATP-sensitive potassium channels in cerebral arterioles. Stroke 29:817–822; discussion 823.

    PubMed  Google Scholar 

  • Wendon, J.A., Harrison, P.M., Keays, R., and Williams, R. (1994). Cerebral blood flow and metabolism in fulminant liver failure. Hepatology 19:1407–1413.

    PubMed  Google Scholar 

  • Wiencken, A.E., and Casagrande, V.A. (1999). Endothelial nitric oxide synthetase (eNOS) in astrocytes: Another source of nitric oxide in neocortex. Glia 26:280–290.

    PubMed  Google Scholar 

  • Wigmore, S.J., Walsh, T.S., Lee, A., and Ross, J.A. (1998). Pro-inflammatory cytokine release and mediation of the acute phase protein response in fulminant hepatic failure. Intens. Care Med. 24:224–229.

    Google Scholar 

  • Zakhary, R., Gaine, S.P., Dinerman, J.L., Ruat, M., Flavahan, N.A., and Snyder, S.H. (1996). Heme oxygenase 2: Endothelial and neuronal localization and role in endothelium-dependent relaxation. Proc. Natl. Acad. Sci. U. S. A. 93:795–798.

    PubMed  Google Scholar 

  • Zwingmann, C., Chatauret, N., Leibfritz, D., and Butterworth, R.F. (2003). Selective increase of brain lactate synthesis in experimental acute liver failure: Results of a [H-C] nuclear magnetic resonance study. Hepatology 37:420–428.

    PubMed  Google Scholar 

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  1. Hepatology Section, Lakeside VA Medical Center and Northwestern University Feinberg School of Medicine, Chicago, Illinois

    Javier Vaquero, Chuhan Chung & Andres T. Blei

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  1. Javier Vaquero
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  2. Chuhan Chung
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Vaquero, J., Chung, C. & Blei, A.T. Cerebral Blood Flow in Acute Liver Failure: A Finding in Search of a Mechanism. Metab Brain Dis 19, 177–194 (2004). https://doi.org/10.1023/B:MEBR.0000043968.04313.e7

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