Neuroinflammation in hepatic encephalopathy: Mechanistic aspects

Journal of Clinical and Experimental Hepatology

Volumn 5, Issue S1, 2015, Pages S21-S28

  Jayakumar, Arumugam R ^a   Rama Rao, Kakulavarapu V ^b   Norenberg, Michael D ^a,b  

^a VETERANS AFFAIRS MEDICAL CENTER   (United States)

^b UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

Author keywords

Ammonia; Hepatic encephalopathy; Neuroinflammation

Indexed keywords

AMMONIA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; TOLL LIKE RECEPTOR 4;

ACUTE DISEASE; ASTROCYTE; BRAIN EDEMA; CELL ACTIVATION; CELL SWELLING; CHRONIC DISEASE; CYTOKINE PRODUCTION; DISEASE ACTIVITY; DISEASE ASSOCIATION; ENDOTHELIUM CELL; HEPATIC ENCEPHALOPATHY; HUMAN; IN VIVO STUDY; MICROGLIA; NERVOUS SYSTEM INFLAMMATION; NEUROTOXICITY; NONHUMAN; PRIORITY JOURNAL; REVIEW;

EID: 84924582553     PISSN: 09736883     EISSN: 22133453     Source Type: Journal    
DOI: 10.1016/j.jceh.2014.07.006     Document Type: Review

References (82)

1. Lockwood A.H., Yap E.W., Wong W.H. Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephalopathy. JCereb Blood Flow Metab 1991, 11:337-341.
2. Norenberg M.D. The astrocyte in liver disease. Advances in Cellular Neurobiology 1981, Vol. 2:303-352. Academic Press, New York.
3. Martin H., Voss K., Hufnagl P., Wack R., Wassilew G. Morphometric and densitometric investigations of protoplasmic astrocytes and neurons in human hepatic encephalopathy. Exp Pathol 1987, 32:241-250.
4. Lee W.M. Acute liver failure. Semin Respir Crit Care Med 2012, 33:36-45.
5. Jalan R., Olde Damink S.W., Hayes P.C., Deutz N.E., Lee A. Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow. JHepatol 2004, 41:613-620.
6. Larsen F.S., Hansen B.A., Blei A.T. Intensive care management of patients with acute liver failure with emphasis on systemic hemodynamic instability and cerebral edema: a critical appraisal of pathophysiology. Can J Gastroenterol 2000, 14(suppl D):105D-111D.
7. Shawcross D.L., Wendon J.A. The neurological manifestations of acute liver failure. Neurochem Int 2012, 60:662-671.
8. Norenberg M.D. Alight and electron microscopic study of experimental portal-systemic (ammonia) encephalopathy. Progression and reversal of the disorder. Lab Invest 1977, 36:618-627.
9. Voorhies T.M., Ehrlich M.E., Duffy T.E., Petito C.K., Plum F. Acute hyperammonemia in the young primate. Physiologic and neuropathological correlates. Pediatr Res 1983, 17:970-975.
10. Traber P.G., Dal Canto M.C., Ganger D., Blei A.T. Electron microscopic evaluation of brain edema in rabbits with galactosamine-induced fulminant hepatic failure: ultrastructure and integrity of the blood-brain barrier. Hepatology 1987, 7:1272-1277.
11. Swain M.S., Blei A.T., Butterworth R.F., Kraig R.P. Intracellular pH rises and astrocytes swell after portacaval anastomosis in rats. Am J Physiol Regul Integr Comp Physiol 1991, 261:R1491-R1496.
12. Kato M., Hughes R.D., Keays R.T., Williams R. Electron microscopic study of brain capillaries in cerebral edema from fulminant hepatic failure. Hepatology 1992, 15:1060-1066.
13. Norenberg M.D. The role of astrocytes in hepatic encephalopathy. Neurochem Pathol 1987, 6:13-33.
14. Martinez-Hernandez A., Bell K.P., Norenberg M.D. Glutamine synthetase: glial localization in brain. Science 1977, 195:1356-1358.
15. Norenberg M.D., Neary J.T., Bender A.S., Dombro R.S. Hepatic encephalopathy: a disorder in glial-neuronal communication. Prog Brain Res 1992, 94:261-269.
16. Conn H., Lieberthal M. The Hepatic Coma Syndrome and Lactulose 1978, Williams & Wilkins Co, Baltimore.
17. Gregorios J.B., Mozes L.W., Norenberg L.O.B., Norenberg M.D. Morphologic effects of ammonia on primary astrocyte cultures. I: light microscopic studies. JNeuropathol Exp Neurol 1985, 44:397-403.
18. Gregorios J.B., Mozes L.W., Norenberg M.D. Morphologic effects of ammonia on primary astrocyte cultures. II: electron microscopic studies. JNeuropathol Exp Neurol 1985, 44:404-414.
19. Blei A.T., Olafsson S., Therrien G., Butterworth R.F. Ammonia-induced brain edema and intracranial hypertension in rats after portacaval anastomosis. Hepatology 1994, 19:1437-1444.
20. Clemmesen J.O., Larsen F.S., Kondrup J., Hansen B.A., Ott P. Cerebral herniation in acute liver failure is correlated with arterial ammonia concentration. Hepatology 1999, 29:648-653.
21. Coltart I., Tranah T.H., Shawcross D.L. Inflammation and hepatic encephalopathy. Arch Biochem Biophys 2013 Aug 15, 536(2):189-196.
22. Odeh M. Pathogenesis of hepatic encephalopathy: the tumour necrosis factor-alpha theory. Eur J Clin Invest 2007, 37:291-304.
23. Norenberg M.D., Rama Rao K.V., Jayakumar A.R. Signaling factors in the mechanism of ammonia neurotoxicity. Metab Brain Dis 2009, 24:103-117.
24. Norenberg M.D., Jayakumar A.R., Rama Rao K.V., Panickar K.S. New concepts in the mechanism of ammonia-induced astrocyte swelling. Metab Brain Dis 2007, 22:219-234.
25. Rama Rao K.V., Jayakumar A.R., Norenberg M.D. Brain edema in acute liver failure: mechanisms and concepts. Metab Brain Dis 2014, In press.
26. Bodega G., Suárez I., Almonacid L., et al. Effect of ammonia on ciliary neurotrophic factor mRNA and protein expression and its upstream signalling pathway in cultured rat astroglial cells: possible implication of c-fos, Sp1 and p38MAPK. Neuropathol Appl Neurobiol 2007, 33:420-430.
27. Konopacka A., Konopacki F.A., Albrecht J. Protein kinase G is involved in ammonia-induced swelling of astrocytes. JNeurochem 2009, 109(suppl 1):246-251.
28. Aspinall R.J., Weis S.M., Barnes L., et al. ASrc family kinase inhibitor improves survival in experimental acute liver failure associated with elevated cerebral and circulating vascular endothelial growth factor levels. Liver Int 2011, 31:1222-1230.
29. Panickar K.S., Jayakumar A.R., Rao K.V., Norenberg M.D. Ammonia-induced activation of p53 in cultured astrocytes: role in cell swelling and glutamate uptake. Neurochem Int 2009, 55:98-105.
30. Schliess F., Görg B., Fischer R., et al. Ammonia induces MK-801-sensitive nitration and phosphorylation of protein tyrosine residues in rat astrocytes. FASEB J 2002, 16:739-741.
31. Sinke A.P., Jayakumar A.R., Panickar K.S., Moriyama M., Reddy P.V., Norenberg M.D. NFkappaB in the mechanism of ammonia-induced astrocyte swelling in culture. JNeurochem 2008, 106:2302-2311.
32. Jayakumar A.R., Bethea J.R., Tong X.Y., Gomez J., Norenberg M.D. NF-κB in the mechanism of brain edema in acute liver failure: studies in transgenic mice. Neurobiol Dis 2011, 41:498-507.
33. Jayakumar A.R., Liu M., Moriyama M., et al. Na-K-Cl Cotransporter-1 in the mechanism of ammonia-induced astrocyte swelling. JBiol Chem 2008, 283:33874-33882.
34. Jayakumar A.R., Valdes V., Norenberg M.D. The Na-K-Cl cotransporter in the brain edema of acute liver failure. JHepatol 2011, 54:272-278.
35. Jayakumar A.R., Valdes V., Tong X.Y., Shamaladevi N., Gonzalez W., Norenberg M.D. Sulfonylurea receptor 1 contributes to the astrocyte swelling and brain edema in acute liver failure. Transl Stroke Res 2014, 5:28-37.
36. Rama Rao K.V., Jayakumar A.R., Tong X., Curtis K.M., Norenberg M.D. Brain aquaporin-4 in experimental acute liver failure. JNeuropathol Exp Neurol 2010, 69:869-879.
37. Gans H., Mori K., Lindsey E., et al. Septicemia as a manifestation of acute liver failure. Surg Gynecol Obstet 1971, 132:783-790.
38. Wilkinson S.P., Arroyo V., Gazzard B.G., Moodie H., Williams R. Relation of renal impairment and haemorrhagic diathesis to endotoxaemia in fulminant hepatic failure. Lancet 1974, 1:521-524.
39. Liehr H., Grün M., Brunswig D. Endotoxaemia in acute hepatic failure. Acta Hepatogastroenterol (Stuttg) 1976, 23:235-240.
40. Wyke R.J., Canalese J.C., Gimson A.E., Williams R. Bacteraemia in patients with fulminant hepatic failure. Liver 1982, 2:45-52.
41. Izumi S., Hughes R.D., Langley P.G., Pernambuco J.R., Williams R. Acute phase response after liver transplantation for fulminant hepatic failure and cirrhosis. Transpl Int 1995, 8:340-345.
42. Wigmore S.J., Walsh T.S., Lee A., Ross J.A. Pro-inflammatory cytokine release and mediation of the acute phase protein response in fulminant hepatic failure. Intensive Care Med 1998, 24:224-229.
43. Wright G., Shawcross D., Olde Damink S.W., Jalan R. Brain cytokine flux in acute liver failure and its relationship with intracranial hypertension. Metab Brain Dis 2007, 22:375-388.
44. Banks W.A., Kastin A.J., Broadwell R.D. Passage of cytokines across the blood-brain barrier. Neuroimmunomodulation 1995, 2:241-248.
45. Chung C., Gottstein J., Blei A.T. Indomethacin prevents the development of experimental ammonia-induced brain edema in rats after portacaval anastomosis. Hepatology 2001, 34:249-254.
46. Clemmesen J.O., Hansen B.A., Larsen F.S. Indomethacin normalizes intracranial pressure in acute liver failure: a twenty-three-year-old woman treated with indomethacin. Hepatology 1997, 26:1423-1425.
47. Jiang W., Desjardins P., Butterworth R.F. Direct evidence for central proinflammatory mechanisms in rats with experimental acute liver failure: protective effect of hypothermia. JCereb Blood Flow Metab 2009, 29:944-952.
48. Böcker R., Estler C.J., Ludewig-Sandig D. Evaluation of the hepatotoxic potential of minocycline. Antimicrob Agents Chemother 1991, 35:1434.
49. Malcolm A., Heap T.R., Eckstein R.P., Lunzer M.R. Minocycline-induced liver injury. Am J Gastroenterol 1996, 91:1641-1653.
50. Bemeur C., Qu H., Desjardins P., Butterworth R.F. IL-1 or TNF receptor gene deletion delays onset of encephalopathy and attenuates brain edema in experimental acute liver failure. Neurochem Int 2010, 56:213-215.
51. Chastre A., Bélanger M., Beauchesne E., Nguyen B.N., Desjardins P., Butterworth R.F. Inflammatory cascades driven by tumor necrosis factor-alpha play a major role in the progression of acute liver failure and its neurological complications. PLoS One 2012, 7:e49670.
52. Butterworth R.F. The liver-brain axis in liver failure: neuroinflammation and encephalopathy. Nat Rev Gastroenterol Hepatol 2013, 10:522-528.
53. Rama Rao K.V., Jayakumar A.R., Tong X., Alvarez V.M., Norenberg M.D. Marked potentiation of cell swelling by cytokines in ammonia-sensitized cultured astrocytes. JNeuroinflammation 2010, 7:66.
54. Frank-Cannon T.C., Alto L.T., McAlpine F.E., Tansey M.G. Does neuroinflammation fan the flame in neurodegenerative diseases?. Mol Neurodegener 2009, 4:47.
55. Chastre A., Jiang W., Desjardins P., Butterworth R.F. Ammonia and proinflammatory cytokines modify expression of genes coding for astrocytic proteins implicated in brain edema in acute liver failure. Metab Brain Dis 2010, 25:17-21.
56. Rodrigo R., Cauli O., Gomez-Pinedo U., et al. Hyperammonemia induces neuroinflammation that contributes to cognitive impairment in rats with hepatic encephalopathy. Gastroenterology 2010, 139:675-684.
57. Garden G.A., Möller T. Microglia biology in health and disease. JNeuroimmune Pharmacol 2006, 1:127-137.
58. Görg B., Bidmon H.J., Häussinger D. Gene expression profiling in the cerebral cortex of patients with cirrhosis with and without hepatic encephalopathy. Hepatology 2013, 57:2436-2447.
59. Butterworth R.F. Neuroinflammation in acute liver failure: mechanisms and novel therapeutic targets. Neurochem Int 2011, 59:830-836.
60. Rao K.V., Brahmbhatt M., Norenberg M.D. Microglia contribute to ammonia-induced astrocyte swelling in culture. Metab Brain Dis 2013, 28:139-143.
61. Khanna A., Kahle K.T., Walcott B.P., Gerzanich V., Simard J.M. Disruption of ion homeostasis in the neurogliovascular unit underlies the pathogenesis of ischemic cerebral edema. Transl Stroke Res 2014, 5:3-16.
62. Rangroo Thrane V., Thrane A.S., Chang J., Alleluia V., Nagelhus E.A., Nedergaard M. Real-time analysis of microglial activation and motility in hepatic and hyperammonemic encephalopathy. Neuroscience 2012, 220:247-255.
63. Nguyen J.H., Yamamoto S., Steers J., et al. Matrix metalloproteinase-9 contributes to brain extravasation and edema in fulminant hepatic failure mice. JHepatol 2006, 44:1105-1114.
64. Jayakumar A.R., Ruiz-Cordero R., Tong X.Y., Norenberg M.D. Brain edema in acute liver failure: role of neurosteroids. Arch Biochem Biophys 2013, 536:171-175.
65. Hermenegildo C., Marcaida G., Montoliu C., Grisolía S., Miñana M.D., Felipo V. NMDA receptor antagonists prevent acute ammonia toxicity in mice. Neurochem Res 1996, 21:1237-1244.
66. Paul V., Jayakumar A.R. Independent and combined effects of L-arginine and diazepam on ammonium chloride-induced convulsions in rats. Indian J Physiol Pharmacol 1999, 43:199-204.
67. Vanaja P., Jayakumar A.R. Evidence for an involvement of the ammonia-decreasing action of L-arginine in suppressing picrotoxin-induced convulsions in rats and its additive action with diazepam. Neurol Res 2001, 23:622-626.
68. Chen J.R., Wang B.N., Tseng G.F., Wang Y.J., Huang Y.S., Wang T.J. Morphological changes of cortical pyramidal neurons in hepatic encephalopathy. BMC Neurosci 2014, 15:15.
69. D'Mello C., Le T., Swain M.G. Cerebral microglia recruits monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation. JNeurosci 2009, 29:2089-2102.
70. Agusti A., Cauli O., Rodrigo R., Llansola M., Hernández-Rabaza V., Felipo V. p38 MAP kinase is a therapeutic target for hepatic encephalopathy in rats with portacaval shunts. Gut 2011, 60:1572-1579.
71. Zemtsova I., Görg B., Keitel V., Bidmon H.J., Schrör K., Häussinger D. Microglia activation in hepatic encephalopathy in rats and humans. Hepatology 2011, 54:204-215.
72. Wright G.A., Sharifi Y., Newman T.A., et al. Characterisation of temporal microglia and astrocyte immune responses in bile duct-ligated rat models of cirrhosis. Liver Int 2014, In press.
73. Brück J., Görg B., Bidmon H.J., et al. Locomotor impairment and cerebrocortical oxidative stress in portal vein ligated rats invivo. JHepatol 2011, 54:251-257.
74. Jayakumar A.R., Panickar K.S., Murthy ChR., Norenberg M.D. Oxidative stress and mitogen-activated protein kinase phosphorylation mediate ammonia-induced cell swelling and glutamate uptake inhibition in cultured astrocytes. JNeurosci 2006, 26:4774-4784.
75. Jayakumar A.R., Rama Rao K.V., Tong X.Y., Norenberg M.D. Calcium in the mechanism of ammonia-induced astrocyte swelling. JNeurochem 2009, 109(suppl 1):252-257.
76. Feuerstein G.Z., Wang X., Barone F.C. The role of cytokines in the neuropathology of stroke and neurotrauma. Neuroimmunomodulation 1998, 5:143-159.
77. Jayakumar A.R., Tong X.Y., Ospel J., Norenberg M.D. Role of cerebral endothelial cells in the astrocyte swelling and brain edema associated with acute hepatic encephalopathy. Neuroscience 2012, 218:305-316.
78. Jayakumar A.R., Norenberg M.D. Endothelial-astrocytic interactions in acute liver failure. Metab Brain Dis 2013, 28:183-186.
79. Jayakumar A.R., Tong X.Y., Curtis K.M., Ruiz-Cordero R., Abreu M.T., Norenberg M.D. Increased toll-like receptor 4 in cerebral endothelial cells contributes to the astrocyte swelling and brain edema in acute hepatic encephalopathy. JNeurochem 2014, 128:890-903.
80. Skowrońska M., Zielińska M., Wójcik-Stanaszek L., et al. Ammonia increases paracellular permeability of rat brain endothelial cells by a mechanism encompassing oxidative/nitrosative stress and activation of matrix metalloproteinases. JNeurochem 2012, 121:125-134.
81. Hashimoto M., Ishikawa Y., Yokota S., Goto F., Bando T., Sakakibara Y. Action site of circulating interleukin-1 on the rabbit brain. Brain Res 1991, 540:217-223.
82. Matsumura K., Kobayashi S. Signaling the brain in inflammation: the role of endothelial cells. Front Biosci 2004, 9:2819-2826.