{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T17:09:01Z","timestamp":1789924141846,"version":"4.0.1"},"reference-count":217,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hepatic encephalopathy (HE) is a neurological complication of liver disease resulting in cognitive, psychiatric, and motor symptoms. Although hyperammonemia is a key factor in the pathogenesis of HE, several other factors have recently been discovered. Among these, the impairment of a highly organized perivascular network known as the glymphatic pathway seems to be involved in the progression of some neurological complications due to the accumulation of misfolded proteins and waste substances in the brain interstitial fluids (ISF). The glymphatic system plays an important role in the clearance of brain metabolic derivatives and prevents aggregation of neurotoxic agents in the brain ISF. Impairment of it will result in aggravated accumulation of neurotoxic agents in the brain ISF. This could also be the case in patients with liver failure complicated by HE. Indeed, accumulation of some metabolic by-products and agents such as ammonia, glutamine, glutamate, and aromatic amino acids has been reported in the human brain ISF using microdialysis technique is attributed to worsening of HE and correlates with brain edema. Furthermore, it has been reported that the glymphatic system is impaired in the olfactory bulb, prefrontal cortex, and hippocampus in an experimental model of HE. In this review, we discuss different factors that may affect the function of the glymphatic pathways and how these changes may be involved in HE.<\/jats:p>","DOI":"10.3390\/cells12070979","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T05:19:24Z","timestamp":1679548764000},"page":"979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The Glymphatic System May Play a Vital Role in the Pathogenesis of Hepatic Encephalopathy: A Narrative Review"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5550-3639","authenticated-orcid":false,"given":"Ali","family":"Sepehrinezhad","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran 1449614535, Iran"},{"name":"Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad 9919191778, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fin","family":"Stolze Larsen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Rigshospitalet, Copenhagen University Hospital, 999017 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rezan","family":"Ashayeri Ahmadabad","sequence":"additional","affiliation":[{"name":"Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran 1449614535, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5222-4792","authenticated-orcid":false,"given":"Ali","family":"Shahbazi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran 1449614535, Iran"},{"name":"Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2242-9794","authenticated-orcid":false,"given":"Sajad","family":"Sahab Negah","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad 9919191778, Iran"},{"name":"Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran 1449614535, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1056\/NEJMra1600561","article-title":"Hepatic Encephalopathy","volume":"375","author":"Wijdicks","year":"2016","journal-title":"N. 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