1. Felipo V. Hepatic encephalopathy: effects of liver failure on brain function. Nat Rev Neurosci. 2013; 14: 851-8. [DOI:10.1038/nrn3587]

2. Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American association for the study of liver diseases and the european association for the study of the liver. Hepatology. 2014; 60(2): 715-35. [DOI:10.1002/hep.27210]

3. Aldridge DR, Tranah EJ, Shawcross DL. Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation. J Clin Exp Hepatol. 2015; 5(1): S7-S20. [DOI:10.1016/j.jceh.2014.06.004]

4. Cauli O, Rodrigo R, Llansola M, Montoliu C, Monfort P, Piedrafita B, et al. Glutamatergic and gabaergic neurotransmission and neuronal circuits in hepatic encephalopathy. Metab Brain Dis. 2009; 24(1): 69-80. [DOI:10.1007/s11011-008-9115-4]

5. Llansola M, Montoliu C, Cauli O, Hernandez-Rabaza V, Agusti A, Cabrera-Pastor A, et al. Chronic hyperammonemia, glutamatergic neurotransmission and neurological alterations. Metab Brain Dis. 2013; 28(2): 151-4. [DOI:10.1007/s11011-012-9337-3]

6. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, and Blei AT. Hepatic encephalopathy--definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002; 35(3): 716-21. [DOI:10.1053/jhep.2002.31250]

7. Savlan I, Liakina V, Valantinas J. Concise review of current concepts on nomenclature and pathophysiology of hepatic encephalopathy. Medicina (Kaunas). 2014; 50(2): 75-81. [DOI:10.1016/j.medici.2014.06.008]

8. Acharya C, Bajaj JS. Current management of hepatic encephalopathy. Am J Gastroenterol. 2018; doi: 10.1038/s41395-018-0179-4. [DOI:10.1038/s41395-018-0179-4]

9. Butterworth RF. Pathophysiology of hepatic encephalopathy: the concept of synergism. Hepatol Res. 2008; 38(1): 116-21. [DOI:10.1111/j.1872-034X.2008.00436.x]

10. Rose CF. Ammonia-lowering strategies for the treatment of hepatic encephalopathy. Clin Pharmacol Ther. 2012; 92(3): 321-31. [DOI:10.1038/clpt.2012.112]

11. Shawcross DL. Diagnosis and management of hepatic encephalopathy. Br J Nurs. 2018; 27(3): S7-S13. [DOI:10.12968/bjon.2018.27.Sup3.S7]

12. Hadjihambi A, Arias N, Sheikh M, Jalan R. Hepatic encephalopathy: a critical currentreview. Hepatol Int. 2018; 12(1): 135-47. [DOI:10.1007/s12072-017-9812-3]

13. Swaminathan M, Ellul MA, Cross TJ. Hepatic encephalopathy: current challenges and future prospects. Hepat Med. 2018; 10: 1-11. [DOI:10.2147/HMER.S118964]

14. Parkash O, Ayub A, Hamid S. Hepatic encephalopathy. Brzozowski T. New dvances in the basic and clinical gastroenterology. 1st ed. InTech. 2012; p. 566.

15. Dasarathy S, Mookerjee RP, Rackayova V, Rangroo Thrane V, Vairappan B, Ott P, et al. Ammonia toxicity: from head to toe? Metab Brain Dis. 2017; 32(2): 529-38. [DOI:10.1007/s11011-016-9938-3]

16. Cooper AJ, Jeitner TM. Central role of glutamate metabolism in the maintenance of nitrogen homeostasis in normal and hyperammonemic brain. Biomolecules. 2016; 6(2): doi: 10.3390/biom6020016. [DOI:10.3390/biom6020016]

17. Prakash R, Mullen KD. Mechanisms, diagnosis and managementof hepatic encephalopathy. Nat Rev Gastroenterol Hepatol. 2010; 7(9): 515-25. [DOI:10.1038/nrgastro.2010.116]

18. Coltart I, Tranah TH, Shawcross DL. Inflammation and hepatic encephalopathy. Arch Biochem Biophys. 2013; 536(2): 189-96. [DOI:10.1016/j.abb.2013.03.016]

19. Jayakumar AR, Rama Rao KV, Norenberg MD. Neuroinflammation in hepatic encephalopathy: mechanistic aspects. J Clin Exp Hepatol. 2015; 5(1): S21-8. [DOI:10.1016/j.jceh.2014.07.006]

20. Wigmore SJ, Walsh TS, Lee A, Ross JA. Pro-inflammatory cytokine release and mediation of the acute phase protein response in fulminant hepatic failure. Intensive Care Med. 1998; 24(3): 224-9. [DOI:10.1007/s001340050554]

21. Wright G, Shawcross D, Olde Damink SW, Jalan R. Brain cytokine flux in acute liver failure and its relationship with intracranial hypertension. Metab Brain Dis. 2007; 22(3-4): 375-88. [DOI:10.1007/s11011-007-9071-4]

22. Cauli O, Rodrigo R, Piedrafita B, Boix J, Felipo V. Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts. Hepatology. 2007; 46(2): 514-9. [DOI:10.1002/hep.21734]

23. Ciecko-Michalska I, Szczepanek M, Slowik A, Mach T. Pathogenesis of hepatic encephalopathy. Gastroenterol Res Pract. 2012; 2012: 642108. [DOI:10.1155/2012/642108]

24. Bosoi CR, Rose CF. Oxidative stress: a systemic factor implicated in the pathogenesis of hepatic encephalopathy. Metab Brain Dis. 2013; 28(2): 175-8. [DOI:10.1007/s11011-012-9351-5]

25. Seyan AS, Hughes RD, Shawcross DL. Changing face of hepatic encephalopathy: role of inflammation and oxidative stress. World J Gastroenterol. 2010; 16(27): 3347-57. [DOI:10.3748/wjg.v16.i27.3347]

26. Cabrera-Pastor A, Llansola M, Reznikov V, Boix J, Felipo V. Differential effects of chronic hyperammonemia onmodulation of the glutamate-nitric oxide-cGMP pathway by metabotropic glutamate receptor 5 and low and high affinity AMPA receptors in cerebellum in vivo. Neurochem Int. 2012; 61(1): 63-71. [DOI:10.1016/j.neuint.2012.04.006]

27. Cauli O, Mansouri MT, Agusti A, Felipo V. Hyperammonemia increases GABAergic tone in the cerebellum but decreases it in the rat cortex. Gastroenterology. 2009; 136(4): 1359-67, e1-2.

28. Cauli O, Mlili N, Rodrigo R, Felipo V. Hyperammonaemia alters the mechanisms by which metabotropic glutamate receptors in nucleus accumbens modulate motor function. J Neurochem. 2007; 103(1): 38-46. [DOI:10.1111/j.1471-4159.2007.04734.x]

29. Llansola M, Rodrigo R, Monfort P, Montoliu C, Kosenko E, Cauli O, et al. NMDA receptors in hyperammonemia and hepatic encephalopathy. Metab Brain Dis. 2007; 22(3-4): 321-35. [DOI:10.1007/s11011-007-9067-0]

30. Vogels BA, Maas MA, Daalhuisen J, Quack G, Chamuleau RA. Memantine, a noncompetitive NMDA receptor antagonist improves hyperammonemia-induced encephalopathy and acute hepatic encephalopathy in rats. Hepatology. 1997; 25(4): 820-7. [DOI:10.1002/hep.510250406]

31. Boix J, Llansola M, Cabrera-Pastor A, Felipo V. Metabotropic glutamate receptor 5 modulates the nitric oxide-cGMP pathway in cerebellum in vivo through activation of AMPA receptors. Neurochem Int. 2011; 58(5): 599-604. [DOI:10.1016/j.neuint.2011.01.025]

32. Cabrera-Pastor A, Taoro-Gonzalez L, Lopez-Merino E, Celma F, Llansola M, Felipo V. Chronic hyperammonemia alters in opposite ways membrane expression of GluA1 and GluA2 AMPA receptor subunits in cerebellum. Molecular mechanisms involved. Biochim Biophys Acta Mol Basis Dis. 2018; 1864(1): 286-95. [DOI:10.1016/j.bbadis.2017.10.031]

33. Felipo V, Piedrafita B, Barios JA, Agusti A, Ahabrach H, Romero-Vives M, et al. Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein kinase activity in hypothalamus correlating with circadian rhythms alterations. Chronobiol Int. 2015; 32(7): 966-79.

34. Tahmasebi S. Gene expression of calcium-calmodulin dependent protein kinase IIα in brain of rat model with hepatic encephalopathy. MSc Thesis. Iran: University of Kurdistan. 2015.

35. Saito N, Shirai Y. Protein kinase C gamma (PKC gamma): function of neuron specific isotype. J Biochem. 2002; 132(5): 683-7. [DOI:10.1093/oxfordjournals.jbchem.a003274]

36. Felipo V, Kosenko E, Minana MD, Marcaida G, Grisolia S. Molecular mechanism of acute ammonia toxicity and of its prevention by L-carnitine. Adv Exp Med Biol. 1994; 368: 65-77. [DOI:10.1007/978-1-4615-1989-8_7]

37. Felipo V, Hermenegildo C, Montoliu C, Llansola M, Minana MD. Neurotoxicity of ammonia and glutamate: molecular mechanisms and prevention. Neurotoxicology. 1998; 19(4-5): 675-81.

38. Faridi S. Gene expression of protein kinase Cγ in brain of rat with hepatic encephalopathy. MSc Thesis. Iran: University of Kurdistan. 2015.

39. Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev. 2011; 75(1): 50-83. [DOI:10.1128/MMBR.00031-10]

40. McKay MM, Morrison DK. Integrating signals from RTKs to ERK/MAPK. Oncogene. 2007; 26(22): 3113-21. [DOI:10.1038/sj.onc.1210394]

41. Morrison DK. MAP kinase pathways. Cold Spring Harb Perspect Biol. 2012; 4: a011254. [DOI:10.1101/cshperspect.a011254]

42. Hommes DW, Peppelenbosch MP, van Deventer SJ. Mitogen activated protein (MAP)kinase signal transduction pathways and novel anti-inflammatory targets. Gut. 2003; 52(1): 144-51. [DOI:10.1136/gut.52.1.144]

43. Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 2004; 68(2): 320-44. [DOI:10.1128/MMBR.68.2.320-344.2004]

44. Taoro-Gonzalez L, Arenas YM, Cabrera-Pastor A, Felipo V. Hyperammonemia alters membrane expression of GluA1 and GluA2 subunits of AMPA receptors in hippocampus by enhancing activation of the IL-1 receptor: underlying mechanisms .J Neuroinflammation. 2018; 15: 36. doi.org/10.1186/s12974-018-1082-z. [DOI:10.1186/s12974-018-1082-z]

45. Agusti A, Cauli O, Rodrigo R, Llansola M, Hernandez-Rabaza V, Felipo V. p38 MAP kinase is a therapeutic target for hepatic encephalopathy in rats with portacaval shunts. Gut. 2011; 60(11): 1572-9. [DOI:10.1136/gut.2010.236083]

46. Kaminska B.MAPK signalling pathways as molecular targets for anti-inflammatory therapy--from molecular mechanisms to therapeutic benefits. Biochim Biophys Acta. 2005; 1754(1-2): 253-62. [DOI:10.1016/j.bbapap.2005.08.017]

47. Zhang J, Gao S, Duan Z, Hu KQ. Overview on acute-on-chronic liver failure.Front Med. 2016; 10(1): 1-17. [DOI:10.1007/s11684-016-0439-x]

48. Fiati Kenston SS, Song X, Li Z, Zhao J. Mechanistic insight, diagnosis, and treatment of ammonia-induced hepatic encephalopathy. J Gastroenterol Hepatol. 2018; doi: 10.1111/jgh.14408. [DOI:10.1111/jgh.14408]

49. Merli M, Iebba V, Giusto M. What is new about diet in hepatic encephalopathy. Metab Brain Dis. 2016; 31(6): 1289-94. [DOI:10.1007/s11011-015-9734-5]

50. Weber FL Jr. Lactulose and combination therapy of hepatic encephalopathy: the role of the intestinal microflora. Dig Dis. 1996; 14(1): 53-63. [DOI:10.1159/000171583]

51. Blanco Vela CI, Poo RamirezJL. Efficacy of oral L-ornithine L-aspartate in cirrhotic patients with hyperammonemic hepatic encephalopathy. Ann Hepatol. 2011; 10(2): S55-9.

52. Jiang Q, Jiang XH, Zheng MH, Chen YP. L-Ornithine-l-aspartate in the management of hepatic encephalopathy: a meta-analysis. J Gastroenterol Hepatol. 2009; 24(1): 9-14. [DOI:10.1111/j.1440-1746.2008.05582.x]

53. Cordoba J. Hepatic encephalopathy: from the pathogenesis to the new treatments. ISRN Hepatol. 2014; 2014: 236268. doi: 10.1155/2014/236268. [DOI:10.1155/2014/236268]

54. Plauth M, Merli M, Kondrup J, Weimann A, Ferenci P, Muller MJ, et al. ESPEN guidelines for nutrition in liver disease and transplantation. Clin Nutr. 1997; 16(2): 43-55. [DOI:10.1016/S0261-5614(97)80022-2]

55. Rodrigo R, Cauli O, Gomez-Pinedo U, Agusti A, Hernandez-Rabaza V, Garcia-Verdugo JM, et al. Hyperammonemia induces neuroinflammation that contributes to cognitive impairment in rats with hepatic encephalopathy. Gastroenterology. 2010; 139(2): 675-84. [DOI:10.1053/j.gastro.2010.03.040]

56. Wijdicks EF. Hepatic encephalopathy. N Engl J Med. 2016; 375: 1660-70. [DOI:10.1056/NEJMra1600561]