Shawcross DL, Davies NA, Williams R, Jalan R. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol. 2004;40(2):247–54. https://doi.org/10.1016/j.jhep.2003.10.016.

Article  CAS  PubMed  Google Scholar 

Blei AT. Infection, inflammation and hepatic encephalopathy, synergism redefined. J Hepatol. 2004;40(2):327–30. https://doi.org/10.1016/j.jhep.2003.12.007.

Article  PubMed  Google Scholar 

Felipo V, Urios A, Montesinos E, Molina I, Garcia-Torres ML, Civera M, Olmo JA, Ortega J, Martinez-Valls J, Serra MA, Cassinello N, Wassel A, Jordá E, Montoliu C. Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy. Metab Brain Dis. 2012;27(1):51–8. https://doi.org/10.1007/s11011-011-9269-3.

Article  CAS  PubMed  Google Scholar 

Aldridge DR, Tranah EJ, Shawcross DL. Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation. J Clin Exp Hepatol. 2015;5(Suppl 1):S7–20. https://doi.org/10.1016/j.jceh.2014.06.004.

Article  PubMed  Google Scholar 

Azhari H, Swain MG. Role of peripheral inflammation in hepatic encephalopathy. J Clin Exp Hepatol. 2018;8(3):281–5. https://doi.org/10.1016/j.jceh.2018.06.008.

Article  PubMed  PubMed Central  Google Scholar 

Häussinger D, Dhiman RK, Felipo V, Görg B, Jalan R, Kircheis G, Merli M, Montagnese S, Romero-Gomez M, Schnitzler A, Taylor-Robinson SD, Vilstrup H. Hepatic encephalopathy. Nat Rev Dis Primers. 2022;8(1):43. https://doi.org/10.1038/s41572-022-00366-6.

Article  PubMed  Google Scholar 

Balzano T, Dadsetan S, Forteza J, Cabrera-Pastor A, Taoro-Gonzalez L, Malaguarnera M, Gil-Perotin S, Cubas-Nuñez L, Casanova B, Castro-Quintas A, Ponce-Mora A, Arenas YM, Leone P, Erceg S, Llansola M, Felipo V. Chronic hyperammonemia induces peripheral inflammation that leads to cognitive impairment in rats: reversed by anti-TNF-α treatment. J Hepatol. 2020;73(3):582–92. https://doi.org/10.1016/j.jhep.2019.01.008.

Article  CAS  PubMed  Google Scholar 

Cabrera-Pastor A, Llansola M, Montoliu C, Malaguarnera M, Balzano T, Taoro-Gonzalez L, García-García R, Mangas-Losada A, Izquierdo-Altarejos P, Arenas YM, Leone P, Felipo V. Peripheral inflammation induces neuroinflammation that alters neurotransmission and cognitive and motor function in hepatic encephalopathy: underlying mechanisms and therapeutic implications. Acta Physiol (Oxf). 2019;226(2): e13270. https://doi.org/10.1111/apha.13270.

Article  CAS  PubMed  Google Scholar 

Arenas YM, Balzano T, Ivaylova G, Llansola M, Felipo V. The S1PR2-CCL2-BDNF-TrkB pathway mediates neuroinflammation and motor incoordination in hyperammonaemia. Neuropathol Appl Neurobiol. 2022;48(4): e12799. https://doi.org/10.1111/nan.12799.

Article  CAS  PubMed  Google Scholar 

Arenas YM, Martínez-García M, Llansola M, Felipo V. Enhanced BDNF and TrkB activation enhance GABA neurotransmission in cerebellum in hyperammonemia. Int J Mol Sci. 2022;23(19):11770. https://doi.org/10.3390/ijms231911770.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Llansola M, Arenas YM, Sancho-Alonso M, Mincheva G, Palomares-Rodriguez A, Doverskog M, Izquierdo-Altarejos P, Felipo V. Neuroinflammation alters GABAergic neurotransmission in hyperammonemia and hepatic encephalopathy, leading to motor incoordination. Mechanisms and therapeutic implications. Front Pharmacol. 2024;15:1358323. https://doi.org/10.3389/fphar.2024.1358323.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Williams GP, Schonhoff AM, Sette A, Lindestam Arlehamn CS. Central and peripheral inflammation: connecting the immune responses of Parkinson’s disease. J Parkinsons Dis. 2022;12(s1):S129–36. https://doi.org/10.3233/JPD-223241.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cossu D, Hatano T, Hattori N. The role of immune dysfunction in Parkinson’s disease development. Int J Mol Sci. 2023;24(23):16766. https://doi.org/10.3390/ijms242316766.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Takeda S, Sato N, Morishita R. Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy. Front Aging Neurosci. 2014;6:171. https://doi.org/10.3389/fnagi.2014.00171.

Article  PubMed  PubMed Central  Google Scholar 

Sun Y, Koyama Y, Shimada S. Inflammation from peripheral organs to the brain: how does systemic inflammation cause neuroinflammation? Front Aging Neurosci. 2022;14: 903455. https://doi.org/10.3389/fnagi.2022.903455.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu X, Nemeth DP, Tarr AJ, Belevych N, Syed ZW, Wang Y, Ismail AS, Reed NS, Sheridan JF, Yajnik AR, Disabato DJ, Zhu L, Quan N. Euflammation attenuates peripheral inflammation-induced neuroinflammation and mitigates immune-to-brain signaling. Brain Behav Immun. 2016;54:140–8. https://doi.org/10.1016/j.bbi.2016.01.018.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tieck MP, Vasilenko N, Ruschil C, Kowarik MC. Peripheral memory B cells in multiple sclerosis vs. double negative B cells in neuromyelitis optica spectrum disorder: disease driving B cell subsets during CNS inflammation. Front Cell Neurosci. 2024;18:1337339. https://doi.org/10.3389/fncel.2024.1337339.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dias-Carvalho A, Sá SI, Carvalho F, Fernandes E, Costa VM. Inflammation as common link to progressive neurological diseases. Arch Toxicol. 2024;98(1):95–119. https://doi.org/10.1007/s00204-023-03628-8.

Article  CAS  PubMed  Google Scholar 

Mangas-Losada A, García-García R, Urios A, Escudero-García D, Tosca J, Giner-Durán R, Serra MA, Montoliu C, Felipo V. Minimal hepatic encephalopathy is associated with expansion and activation of CD4+CD28-, Th22 and Tfh and B lymphocytes. Sci Rep. 2017;7(1):6683. https://doi.org/10.1038/s41598-017-05938-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mangas-Losada A, García-García R, Leone P, Ballester MP, Cabrera-Pastor A, Urios A, Gallego JJ, Martínez-Pretel JJ, Giménez-Garzó C, Revert F, Escudero-García D, Tosca J, Ríos MP, Montón C, Durbán L, Aparicio L, Montoliu C, Felipo V. Selective improvement by rifaximin of changes in the immunophenotype in patients who improve minimal hepatic encephalopathy. J Transl Med. 2019;17(1):293. https://doi.org/10.1186/s12967-019-2046-5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Balzano T, Forteza J, Molina P, Giner J, Monzó A, Sancho-Jiménez J, Urios A, Montoliu C, Felipo V. The cerebellum of patients with steatohepatitis shows lymphocyte infiltration, microglial activation and loss of purkinje and granular neurons. Sci Rep. 2018;8(1):3004. https://doi.org/10.1038/s41598-018-21399-6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Leone P, Arenas YM, Balzano T, Mincheva G, Martinez-Garcia M, Montoliu C, Llansola M, Felipo V. Patients who died with steatohepatitis or liver cirrhosis show neuroinflammation and neuronal loss in hippocampus. Eur J Neurol. 2023;30(10):3032–46. https://doi.org/10.1111/ene.15935.

Article  PubMed  Google Scholar 

Kerfoot SM, D’Mello C, Nguyen H, Ajuebor MN, Kubes P, Le T, Swain MG. TNF-alpha-secreting monocytes are recruited into the brain of cholestatic mice. Hepatology (Baltimore, MD). 2006;43(1):154–62. https://doi.org/10.1002/hep.21003.

Article  PubMed  Google Scholar 

D’Mello C, Le T, Swain MG. Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation. J Neurosci. 2009;29(7):2089–102. https://doi.org/10.1523/JNEUROSCI.3567-08.2009.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kostic M, Dzopalic T, Zivanovic S, Zivkovic N, Cvetanovic A, Stojanovic I, Vojinovic S, Marjanovic G, Savic V, Colic M. IL-17 and glutamate excitotoxicity in the pathogenesis of multiple sclerosis. Scand J Immunol. 2014;79(3):181–6. https://doi.org/10.1111/sji.12147.

Article  CAS  PubMed