{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:58:06Z","timestamp":1792180686371,"version":"4.4.0"},"reference-count":104,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":40,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK135995"],"award-info":[{"award-number":["DK135995"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ajp.amjpathol.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Pathology"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.ajpath.2026.07.014","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T15:11:02Z","timestamp":1788016262000},"update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neurologic Consequences of Liver Disease"],"prefix":"10.1016","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5980-0921","authenticated-orcid":false,"given":"Matthew","family":"McMillin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6725-8844","authenticated-orcid":false,"given":"Kathryn","family":"Rhodes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0511-9778","authenticated-orcid":false,"given":"Sharon","family":"DeMorrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajpath.2026.07.014_bib1","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.jhep.2016.12.003","article-title":"EASL clinical practical guidelines on the management of acute (fulminant) liver failure","volume":"66","author":"European Association for the Study of the Liver Clinical Practice Guidelines Panel","year":"2017","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib2","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ajem.2018.10.032","article-title":"Acute liver failure: a review for emergency physicians","volume":"37","author":"Montrief","year":"2019","journal-title":"Am J Emerg Med"},{"key":"10.1016\/j.ajpath.2026.07.014_bib3","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/S0140-6736(19)31894-X","article-title":"Acute liver failure","volume":"394","author":"Stravitz","year":"2019","journal-title":"Lancet"},{"key":"10.1016\/j.ajpath.2026.07.014_bib4","article-title":"Brain CT scan diagnostic and prognostic value in patients with acute liver failure and cerebral edema: a multicenter cohort study","volume":"7","author":"Cardoso","year":"2025","journal-title":"Crit Care Explor"},{"key":"10.1016\/j.ajpath.2026.07.014_bib5","first-page":"23","article-title":"Portosystemic shunts and refractory hepatic encephalopathy: patient selection and current options","volume":"11","author":"Philips","year":"2019","journal-title":"Hepat Med"},{"key":"10.1016\/j.ajpath.2026.07.014_bib6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s40265-018-1018-z","article-title":"Hepatic encephalopathy: definition, clinical grading and diagnostic principles","volume":"79","author":"Weissenborn","year":"2019","journal-title":"Drugs"},{"key":"10.1016\/j.ajpath.2026.07.014_bib7","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1007\/s12098-023-04694-7","article-title":"Systemic complications secondary to chronic liver disease","volume":"91","author":"Mannion","year":"2024","journal-title":"Indian J Pediatr"},{"key":"10.1016\/j.ajpath.2026.07.014_bib8","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.cld.2021.01.008","article-title":"Diagnosis and management of hepatic encephalopathy","volume":"25","author":"Rudler","year":"2021","journal-title":"Clin Liver Dis"},{"key":"10.1016\/j.ajpath.2026.07.014_bib9","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.cld.2023.03.012","article-title":"Hepatic encephalopathy in acute-on-chronic liver failure","volume":"27","author":"Badal","year":"2023","journal-title":"Clin Liver Dis"},{"key":"10.1016\/j.ajpath.2026.07.014_bib10","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/hep.27210","article-title":"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","volume":"60","author":"Vilstrup","year":"2014","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2026.07.014_bib11","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1053\/j.gastro.2015.03.006","article-title":"United States Drug Induced Liver Injury Network: Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study","volume":"148","author":"Chalasani","year":"2015","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ajpath.2026.07.014_bib12","doi-asserted-by":"crossref","first-page":"617","DOI":"10.14309\/ajg.0000000000001655","article-title":"secular trends in severe idiosyncratic drug-induced liver injury in North America: an update from the Acute Liver Failure Study Group Registry","volume":"117","author":"Rao","year":"2022","journal-title":"Am J Gastroenterol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib13","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1053\/j.gastro.2009.06.006","article-title":"Acute Liver Failure Study Group: Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure","volume":"137","author":"Lee","year":"2009","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ajpath.2026.07.014_bib14","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/S0140-6736(24)00693-7","article-title":"Acute liver failure","volume":"404","author":"Maiwall","year":"2024","journal-title":"Lancet"},{"key":"10.1016\/j.ajpath.2026.07.014_bib15","doi-asserted-by":"crossref","first-page":"5717","DOI":"10.3390\/ijms22115717","article-title":"Pathophysiological aspects of alcohol metabolism in the liver","volume":"22","author":"Hyun","year":"2021","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib16","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/JXX.0000000000001105","article-title":"Hepatic encephalopathy in patients with cirrhosis: key clinical considerations for the nurse practitioner and physician assistant","volume":"37","author":"Hanson","year":"2025","journal-title":"J Am Assoc Nurse Pract"},{"key":"10.1016\/j.ajpath.2026.07.014_bib17","first-page":"24","article-title":"Minimal hepatic encephalopathy in patients with alcohol related and non-alcoholic steatohepatitis related cirrhosis by psychometric hepatic cephalopathy score and critical flicker frequency","volume":"53","author":"Jagtap","year":"2021","journal-title":"Acta Med Indones"},{"key":"10.1016\/j.ajpath.2026.07.014_bib18","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1080\/17474124.2021.1844565","article-title":"Managing cognitive symptoms and fatigue in cholestatic liver disease","volume":"15","author":"Phaw","year":"2021","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib19","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.jhep.2010.05.036","article-title":"Central nervous system dysfunction in primary biliary cirrhosis and its relationship to symptoms","volume":"53","author":"McDonald","year":"2010","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib20","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s12944-024-02108-x","article-title":"Updated mechanisms of MASLD pathogenesis","volume":"23","author":"Li","year":"2024","journal-title":"Lipids Health Dis"},{"key":"10.1016\/j.ajpath.2026.07.014_bib21","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jare.2024.02.007","article-title":"A narrative review about cognitive impairment in metabolic dysfunction\u2013associated steatotic liver disease (MASLD): another matter to face through a holistic approach","volume":"68","author":"Meroni","year":"2025","journal-title":"J Adv Res"},{"key":"10.1016\/j.ajpath.2026.07.014_bib22","article-title":"The burden of non-alcoholic steatohepatitis: a systematic review of health-related quality of life and patient-reported outcomes","volume":"4","author":"Younossi","year":"2022","journal-title":"JHEP Rep"},{"key":"10.1016\/j.ajpath.2026.07.014_bib23","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.3390\/cells12182331","article-title":"Cognitive functions, neurotransmitter alterations, and hippocampal microstructural changes in mice caused by feeding on Western diet","volume":"12","author":"Custodio","year":"2023","journal-title":"Cells"},{"key":"10.1016\/j.ajpath.2026.07.014_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.ab.2022.114696","article-title":"Amino acids, ammonia, and hepatic encephalopathy","volume":"649","author":"Kroupina","year":"2022","journal-title":"Anal Biochem"},{"key":"10.1016\/j.ajpath.2026.07.014_bib25","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s11011-025-01645-3","article-title":"Blood-brain barrier dysfunction in hepatic encephalopathy: pathophysiology, diagnostic assessment and therapeutic perspectives","volume":"40","author":"Le Guennec","year":"2025","journal-title":"Metab Brain Dis"},{"key":"10.1016\/j.ajpath.2026.07.014_bib26","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1080\/19336950.2016.1207024","article-title":"Regulation and function of the SLC38A3\/SNAT3 glutamine transporter","volume":"10","author":"Rubio-Aliaga","year":"2016","journal-title":"Channels (Austin)"},{"key":"10.1016\/j.ajpath.2026.07.014_bib27","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/BF00999698","article-title":"Activities of neuronal and astrocytic marker enzymes in autopsied brain tissue from patients with hepatic encephalopathy","volume":"2","author":"Lavoie","year":"1987","journal-title":"Metab Brain Dis"},{"key":"10.1016\/j.ajpath.2026.07.014_bib28","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2021.578922","article-title":"Disturbance of the glutamate-glutamine cycle, secondary to hepatic damage, compromises memory function","volume":"15","author":"Lim\u00f3n","year":"2021","journal-title":"Front Neurosci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib29","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2022.874750","article-title":"Dysregulation of astrocytic glutamine transport in acute hyperammonemic brain edema","volume":"16","author":"Zieli\u0144ska","year":"2022","journal-title":"Front Neurosci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib30","article-title":"Hyperammonaemia induces mitochondrial dysfunction and neuronal cell death","volume":"4","author":"Angelova","year":"2022","journal-title":"JHEP Rep"},{"key":"10.1016\/j.ajpath.2026.07.014_bib31","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1007\/s12035-020-01985-4","article-title":"Ammonia-induced glial-inflammaging","volume":"57","author":"Bobermin","year":"2020","journal-title":"Mol Neurobiol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib32","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.047134","article-title":"Ammonia inhibits energy metabolism in astrocytes in a rapid and glutamate dehydrogenase 2-dependent manner","volume":"13","author":"Drews","year":"2020","journal-title":"Dis Model Mech"},{"key":"10.1016\/j.ajpath.2026.07.014_bib33","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s11910-025-01415-9","article-title":"Hepatic encephalopathy: current thoughts on pathophysiology and management","volume":"25","author":"Sen","year":"2025","journal-title":"Curr Neurol Neurosci Rep"},{"key":"10.1016\/j.ajpath.2026.07.014_bib34","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jceh.2018.06.007","article-title":"Hyperammonemia in hepatic encephalopathy","volume":"8","author":"Jayakumar","year":"2018","journal-title":"J Clin Exp Hepatol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib35","doi-asserted-by":"crossref","first-page":"7878","DOI":"10.1523\/JNEUROSCI.0315-17.2017","article-title":"Chemokine CCL2-CCR2 signaling induces neuronal cell death via STAT3 activation and IL-1[beta] production after status epilepticus","volume":"37","author":"Tian","year":"2017","journal-title":"J Neurosci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib36","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.cellsig.2010.01.010","article-title":"Tumor necrosis factor-alpha mediated signaling in neuronal homeostasis and dysfunction","volume":"22","author":"Park","year":"2010","journal-title":"Cell Signal"},{"key":"10.1016\/j.ajpath.2026.07.014_bib37","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.4103\/NRR.NRR-D-24-00600","article-title":"Role of astrocytes and microglia in hepatic encephalopathy associated with advanced chronic liver disease: lessons from animal studies","volume":"20","author":"Claeys","year":"2025","journal-title":"Neural Regen Res"},{"key":"10.1016\/j.ajpath.2026.07.014_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.ab.2021.114436","article-title":"A critical review of bile acids and their receptors in hepatic encephalopathy","volume":"643","author":"Williams","year":"2022","journal-title":"Anal Biochem"},{"key":"10.1016\/j.ajpath.2026.07.014_bib39","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1194\/jlr.R054114","article-title":"Intestinal transport and metabolism of bile acids","volume":"56","author":"Dawson","year":"2015","journal-title":"J Lipid Res"},{"key":"10.1016\/j.ajpath.2026.07.014_bib40","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.jhep.2013.01.003","article-title":"Modulation of the fecal bile acid profile by gut microbiota in cirrhosis","volume":"58","author":"Kakiyama","year":"2013","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib41","doi-asserted-by":"crossref","first-page":"s15","DOI":"10.5604\/01.3001.0010.5672","article-title":"The role of the gut microbiota in bile acid metabolism","volume":"16","author":"Ram\u00edrez-P\u00e9rez","year":"2017","journal-title":"Ann Hepatol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib42","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jceh.2018.04.011","article-title":"Bile acids in hepatic encephalopathy","volume":"9","author":"DeMorrow","year":"2019","journal-title":"J Clin Exp Hepatol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib43","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2024.1447878","article-title":"Regulation of bile acids and their receptor FXR in metabolic diseases","volume":"11","author":"Li","year":"2024","journal-title":"Front Nutr"},{"key":"10.1016\/j.ajpath.2026.07.014_bib44","doi-asserted-by":"crossref","first-page":"5004","DOI":"10.3390\/ijms26115004","article-title":"Biological actions of bile acids via cell surface receptors","volume":"26","author":"Kiriyama","year":"2025","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib45","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0317568","article-title":"Activation of S1PR2 on macrophages and the hepatocyte S1PR2\/RhoA\/ROCK1\/MLC2 pathway in vanishing bile duct syndrome","volume":"20","author":"Miyagawa-Hayashino","year":"2025","journal-title":"PLoS One"},{"key":"10.1016\/j.ajpath.2026.07.014_bib46","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.jhep.2010.12.004","article-title":"The bile acid membrane receptor TGR5 as an emerging target in metabolism and inflammation","volume":"54","author":"Pols","year":"2011","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib47","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.3390\/nu12092598","article-title":"TGR5 signaling in hepatic metabolic health","volume":"12","author":"Holter","year":"2020","journal-title":"Nutrients"},{"key":"10.1016\/j.ajpath.2026.07.014_bib48","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1136\/gutjnl-2018-316975","article-title":"TGR5-dependent hepatoprotection through the regulation of biliary epithelium barrier function","volume":"69","author":"Merlen","year":"2020","journal-title":"Gut"},{"key":"10.1016\/j.ajpath.2026.07.014_bib49","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/liv.13201","article-title":"Serum bile acids as marker for acute decompensation and acute-on-chronic liver failure in patients with non-cholestatic cirrhosis","volume":"37","author":"Horvatits","year":"2017","journal-title":"Liver Int"},{"key":"10.1016\/j.ajpath.2026.07.014_bib50","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1136\/gut.18.9.692","article-title":"Serum, cerebrospinal fluid, and brain levels of bile acids in patients with fulminant hepatic failure","volume":"18","author":"Bron","year":"1977","journal-title":"Gut"},{"key":"10.1016\/j.ajpath.2026.07.014_bib51","doi-asserted-by":"crossref","first-page":"617","DOI":"10.3389\/fnins.2017.00617","article-title":"Bile acid signaling pathways from the enterohepatic circulation to the central nervous system","volume":"11","author":"Mertens","year":"2017","journal-title":"Front Neurosci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib52","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fnins.2015.00080","article-title":"Hydrophilic bile acids protect human blood-brain barrier endothelial cells from disruption by unconjugated bilirubin: an in vitro study","volume":"9","author":"Palmela","year":"2015","journal-title":"Front Neurosci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib53","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.ajpath.2015.10.005","article-title":"Bile acid signaling is involved in the neurological decline in a murine model of acute liver failure","volume":"186","author":"McMillin","year":"2016","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/pr.109.002014","article-title":"Xenobiotic, bile acid, and cholesterol transporters: function and regulation","volume":"62","author":"Klaassen","year":"2010","journal-title":"Pharmacol Rev"},{"key":"10.1016\/j.ajpath.2026.07.014_bib55","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1210\/me.2015-1087","article-title":"Suppression of the HPA axis during cholestasis can be attributed to hypothalamic bile acid signaling","volume":"29","author":"McMillin","year":"2015","journal-title":"Mol Endocrinol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib56","doi-asserted-by":"crossref","DOI":"10.1038\/srep40112","article-title":"Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury","volume":"7","author":"Nizamutdinov","year":"2017","journal-title":"Sci Rep"},{"key":"10.1016\/j.ajpath.2026.07.014_bib57","doi-asserted-by":"crossref","first-page":"5982","DOI":"10.3390\/ijms21175982","article-title":"Bile acid signaling in neurodegenerative and neurological disorders","volume":"21","author":"Grant","year":"2020","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib58","doi-asserted-by":"crossref","first-page":"1110.7","DOI":"10.1096\/fasebj.26.1_supplement.1110.7","article-title":"Increased serum bile acids after extrahepatic biliary obstruction causes leakiness to the blood brain barrier via the disruption of tight junctions","volume":"26","author":"DeMorrow","year":"2012","journal-title":"FASEB J"},{"key":"10.1016\/j.ajpath.2026.07.014_bib59","article-title":"Increased intestinal bile acid absorption contributes to age-related cognitive impairment","volume":"5","author":"Ren","year":"2024","journal-title":"Cell Rep Med"},{"key":"10.1016\/j.ajpath.2026.07.014_bib60","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3389\/fnbeh.2015.00070","article-title":"Deletion of mouse FXR gene disturbs multiple neurotransmitter systems and alters neurobehavior","volume":"9","author":"Huang","year":"2015","journal-title":"Front Behav Neurosci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib61","doi-asserted-by":"crossref","first-page":"7750","DOI":"10.3390\/ijms21207750","article-title":"The status of bile acids and farnesoid X receptor in brain and liver of rats with thioacetamide-induced acute liver failure","volume":"21","author":"Czarnecka","year":"2020","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib62","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jcmgh.2018.02.008","article-title":"FXR-mediated cortical cholesterol accumulation contributes to the pathogenesis of type A hepatic encephalopathy","volume":"6","author":"McMillin","year":"2018","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib63","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbadis.2025.167750","article-title":"Farnesoid X receptor activation alleviates hepatic encephalopathy by improving hepatic ammonia metabolism in murine models","volume":"1871","author":"Ye","year":"2025","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"10.1016\/j.ajpath.2026.07.014_bib64","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1046\/j.0953-816x.2001.01634.x","article-title":"An essential role for the H218\/AGR16\/Edg-5\/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability","volume":"14","author":"MacLennan","year":"2001","journal-title":"Eur J Neurosci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib65","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1002\/glia.23663","article-title":"Neural sphingosine 1-phosphate accumulation activates microglia and links impaired autophagy and inflammation","volume":"67","author":"Karunakaran","year":"2019","journal-title":"Glia"},{"key":"10.1016\/j.ajpath.2026.07.014_bib66","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1073\/pnas.1615413114","article-title":"Sphingosine 1-phosphate receptor modulation suppresses pathogenic astrocyte activation and chronic progressive CNS inflammation","volume":"114","author":"Rothhammer","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2026.07.014_bib67","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3389\/fncel.2017.00191","article-title":"Bile acid-mediated sphingosine-1-phosphate receptor 2 signaling promotes neuroinflammation during hepatic encephalopathy in mice","volume":"11","author":"McMillin","year":"2017","journal-title":"Front Cell Neurosci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib68","doi-asserted-by":"crossref","DOI":"10.1111\/nan.12799","article-title":"The S1PR2-CCL2-BDNF-TrkB pathway mediates neuroinflammation and motor incoordination in hyperammonaemia","volume":"48","author":"Arenas","year":"2022","journal-title":"Neuropathol Appl Neurobiol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib69","doi-asserted-by":"crossref","DOI":"10.3390\/ijms242417251","article-title":"Enhanced activation of the S1PR2-IL-1[beta]-Src-BDNF-TrkB pathway mediates neuroinflammation in the hippocampus and cognitive impairment in hyperammonemic rats","volume":"24","author":"Sancho-Alonso","year":"2023","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib70","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1002\/glia.21049","article-title":"The bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain","volume":"58","author":"Keitel","year":"2010","journal-title":"Glia"},{"key":"10.1016\/j.ajpath.2026.07.014_bib71","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1111\/jnc.13243","article-title":"TGR5 signaling reduces neuroinflammation during hepatic encephalopathy","volume":"135","author":"McMillin","year":"2015","journal-title":"J Neurochem"},{"key":"10.1016\/j.ajpath.2026.07.014_bib72","doi-asserted-by":"crossref","first-page":"G749","DOI":"10.1152\/ajpgi.00184.2011","article-title":"Liver-brain inflammation axis","volume":"301","author":"D'Mello","year":"2011","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib73","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bbi.2013.10.009","article-title":"Liver-brain interactions in inflammatory liver diseases: implications for fatigue and mood disorders","volume":"35","author":"D'Mello","year":"2014","journal-title":"Brain Behav Immun"},{"key":"10.1016\/j.ajpath.2026.07.014_bib74","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/liv.12048","article-title":"Contrasting responses of Kupffer cells and inflammatory mononuclear phagocytes to biliary obstruction in a mouse model of cholestatic liver injury","volume":"33","author":"Duwaerts","year":"2013","journal-title":"Liver Int"},{"key":"10.1016\/j.ajpath.2026.07.014_bib75","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.surg.2008.01.008","article-title":"Hepatic macrophages promote the neutrophil-dependent resolution of fibrosis in repairing cholestatic rat livers","volume":"143","author":"Harty","year":"2008","journal-title":"Surgery"},{"key":"10.1016\/j.ajpath.2026.07.014_bib76","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.jhep.2010.07.018","article-title":"NK cells suppress experimental cholestatic liver injury by an interleukin-6-mediated, Kupffer cell-dependent mechanism","volume":"54","author":"Cheng","year":"2011","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib77","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1042\/CS20070328","article-title":"Hepatic NKT cells: friend or foe?","volume":"114","author":"Swain","year":"2008","journal-title":"Clin Sci (Lond)"},{"key":"10.1016\/j.ajpath.2026.07.014_bib78","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1053\/j.gastro.2008.10.027","article-title":"Invariant natural killer T cells suppress the neutrophil inflammatory response in a mouse model of cholestatic liver damage","volume":"136","author":"Wintermeyer","year":"2009","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ajpath.2026.07.014_bib79","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jneuroim.2018.10.012","article-title":"The cerebral endothelial cell as a key regulator of inflammatory processes in sterile inflammation","volume":"326","author":"Ludewig","year":"2019","journal-title":"J Neuroimmunol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib80","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0206389","article-title":"US Drug-Induced Liver Injury Network and the Acute Liver Failure Study Group: Cytokine profiles in acute liver injury-results from the US Drug-Induced Liver Injury Network (DILIN) and the Acute Liver Failure Study Group","volume":"13","author":"Bonkovsky","year":"2018","journal-title":"PLoS One"},{"key":"10.1016\/j.ajpath.2026.07.014_bib81","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1111\/hepr.14175","article-title":"Serum pro-inflammatory cytokine interleukin-6 level is predictive of further decompensation and mortality in liver cirrhosis","volume":"55","author":"Ikeda","year":"2025","journal-title":"Hepatol Res"},{"key":"10.1016\/j.ajpath.2026.07.014_bib82","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/glia.20467","article-title":"Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration","volume":"55","author":"Qin","year":"2007","journal-title":"Glia"},{"key":"10.1016\/j.ajpath.2026.07.014_bib83","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1046\/j.1471-4159.1999.0730309.x","article-title":"Effects of systemic immunogenic insults and circulating proinflammatory cytokines on the transcription of the inhibitory factor kappaB alpha within specific cellular populations of the rat brain","volume":"73","author":"Laflamme","year":"1999","journal-title":"J Neurochem"},{"key":"10.1016\/j.ajpath.2026.07.014_bib84","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1189\/jlb.0310149","article-title":"The regulatory role of nitric oxide in proinflammatory cytokine expression during the induction and resolution of inflammation","volume":"88","author":"Kobayashi","year":"2010","journal-title":"J Leukoc Biol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib85","first-page":"22","article-title":"How the blood talks to the brain parenchyma and the paraventricular nucleus of the hypothalamus during systemic inflammatory and infectious stimuli","volume":"223","author":"Rivest","year":"2000","journal-title":"Proc Soc Exp Biol Med"},{"key":"10.1016\/j.ajpath.2026.07.014_bib86","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1046\/j.1471-4159.1997.69041668.x","article-title":"Regulation of the genes encoding interleukin-6, its receptor, and gp130 in the rat brain in response to the immune activator lipopolysaccharide and the proinflammatory cytokine interleukin-1beta","volume":"69","author":"Valli\u00e8res","year":"1997","journal-title":"J Neurochem"},{"key":"10.1016\/j.ajpath.2026.07.014_bib87","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.jhep.2011.09.014","article-title":"Regulatory T cells suppress sickness behaviour development without altering liver injury in cholestatic mice","volume":"56","author":"Nguyen","year":"2012","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib88","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1523\/JNEUROSCI.3567-08.2009","article-title":"Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation","volume":"29","author":"D'Mello","year":"2009","journal-title":"J Neurosci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib89","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/hep.21003","article-title":"TNF-alpha-secreting monocytes are recruited into the brain of cholestatic mice","volume":"43","author":"Kerfoot","year":"2006","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2026.07.014_bib90","doi-asserted-by":"crossref","DOI":"10.3389\/fnetp.2022.937739","article-title":"Plasticity of monocytes and macrophages in cirrhosis of the liver","volume":"2","author":"Geng","year":"2022","journal-title":"Front Netw Physiol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib91","doi-asserted-by":"crossref","first-page":"6683","DOI":"10.1038\/s41598-017-05938-1","article-title":"Minimal hepatic encephalopathy is associated with expansion and activation of CD4+CD28-, Th22 and Tfh and B lymphocytes","volume":"7","author":"Mangas-Losada","year":"2017","journal-title":"Sci Rep"},{"key":"10.1016\/j.ajpath.2026.07.014_bib92","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1007\/s11011-024-01417-5","article-title":"Role of peripheral inflammation in minimal hepatic encephalopathy","volume":"39","author":"Llansola","year":"2024","journal-title":"Metab Brain Dis"},{"key":"10.1016\/j.ajpath.2026.07.014_bib93","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jhep.2003.10.016","article-title":"Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis","volume":"40","author":"Shawcross","year":"2004","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib94","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1097\/MCG.0b013e31815e7f58","article-title":"IL-6 and IL-18 in blood may discriminate cirrhotic patients with and without minimal hepatic encephalopathy","volume":"43","author":"Montoliu","year":"2009","journal-title":"J Clin Gastroenterol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib95","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1038\/s41598-018-21399-6","article-title":"The cerebellum of patients with steatohepatitis shows lymphocyte infiltration, microglial activation and loss of Purkinje and granular neurons","volume":"8","author":"Balzano","year":"2018","journal-title":"Sci Rep"},{"key":"10.1016\/j.ajpath.2026.07.014_bib96","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241210407","article-title":"Mild cognitive impairment is associated with enhanced activation of Th17 lymphocytes in non-alcoholic fatty liver disease","volume":"24","author":"Fiorillo","year":"2023","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib97","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1566-0702(00)00215-0","article-title":"Functional and chemical anatomy of the afferent vagal system","volume":"85","author":"Berthoud","year":"2000","journal-title":"Auton Neurosci"},{"key":"10.1016\/j.ajpath.2026.07.014_bib98","doi-asserted-by":"crossref","first-page":"E2","DOI":"10.3171\/2018.6.FOCUS18216","article-title":"The vagus afferent network: emerging role in translational connectomics","volume":"45","author":"Hachem","year":"2018","journal-title":"Neurosurg Focus"},{"key":"10.1016\/j.ajpath.2026.07.014_bib99","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.cmet.2012.06.015","article-title":"Hindbrain neurons as an essential hub in the neuroanatomically distributed control of energy balance","volume":"16","author":"Grill","year":"2012","journal-title":"Cell Metab"},{"key":"10.1016\/j.ajpath.2026.07.014_bib100","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1038\/s41467-018-04639-1","article-title":"Gut vagal sensory signaling regulates hippocampus function through multi-order pathways","volume":"9","author":"Suarez","year":"2018","journal-title":"Nat Commun"},{"key":"10.1016\/j.ajpath.2026.07.014_bib101","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.conb.2020.03.006","article-title":"Vagal sensory neurons and gut-brain signaling","volume":"62","author":"Yu","year":"2020","journal-title":"Curr Opin Neurobiol"},{"key":"10.1016\/j.ajpath.2026.07.014_bib102","doi-asserted-by":"crossref","first-page":"7","DOI":"10.15424\/bioelectronmed.2016.00007","article-title":"Cytokine-specific neurograms in the sensory vagus nerve","volume":"3","author":"Steinberg","year":"2016","journal-title":"Bioelectron Med"},{"key":"10.1016\/j.ajpath.2026.07.014_bib103","doi-asserted-by":"crossref","first-page":"E4843","DOI":"10.1073\/pnas.1719083115","article-title":"Identification of cytokine-specific sensory neural signals by decoding murine vagus nerve activity","volume":"115","author":"Zanos","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2026.07.014_bib104","article-title":"Hepatic branch vagotomy modulates the gut-liver-brain axis in murine cirrhosis","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Physiol"}],"container-title":["The American Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944026002403?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944026002403?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:45:49Z","timestamp":1789087549000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002944026002403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":104,"alternative-id":["S0002944026002403"],"URL":"https:\/\/doi.org\/10.1016\/j.ajpath.2026.07.014","relation":{},"ISSN":["0002-9440"],"issn-type":[{"value":"0002-9440","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Neurologic Consequences of Liver Disease","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Pathology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajpath.2026.07.014","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Published by Elsevier Inc. on behalf of the American Society for Investigative Pathology.","name":"copyright","label":"Copyright"}]}}