{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:01:36Z","timestamp":1791900096116,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,8,2]],"date-time":"2013-08-02T00:00:00Z","timestamp":1375401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"The Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Acute liver failure (<jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>) is frequently complicated by infection leading to precipitation of central nervous system complications such as hepatic encephalopathy (<jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content>) and increased mortality. There is evidence to suggest that when infection occurs in <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content> patients, the resulting pro\u2010inflammatory mechanisms may be amplified that could, in turn, have a major impact on blood\u2013brain barrier (<jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>) function. The aim of this study was to investigate the role of endotoxemia on the progression of encephalopathy in relation to <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content> permeability during <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult male C57\u2010<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>6 mice with <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content> resulting from azoxymethane\u2010induced toxic liver injury were administered trace amounts of the endotoxin component lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>). Effects on the magnitude of the systemic inflammatory response, liver pathology and <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content> integrity were measured as a function of progression of <jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content>, defined as time to loss of corneal reflex (coma).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Lipopolysaccharide caused additional two\u2010 to seven\u2010fold (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) increases in circulating pro\u2010inflammatory cytokines (TNF\u2010\u03b1, IL\u20101\u03b2, IL\u20106), worsening liver pathology and associated increases of circulating transaminases as well as increased hyperammonaemia consistent with a further loss of viable hepatocytes. LPS treatment of ALF mice led to a rapid precipitation of hepatic coma and the BBB became permeable to the 25\u2010kDa protein immunoglobulin G (IgG). This extravasation of IgG was accompanied by ignificant up\u2010regulation of matrix metalloproteinase\u20109 (MMP\u20109), an endopeptidase known to modulate opening of the BBB in a wide range of neurological disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings represent the first direct evidence of inflammation\u2010related <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content> permeability changes in <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12252","type":"journal-article","created":{"date-parts":[[2013,6,19]],"date-time":"2013-06-19T11:53:51Z","timestamp":1371642831000},"page":"353-361","source":"Crossref","is-referenced-by-count":52,"title":["Lipopolysaccharide precipitates hepatic encephalopathy and increases blood\u2013brain barrier permeability in mice with acute liver failure"],"prefix":"10.1111","volume":"34","author":[{"given":"Anne","family":"Chastre","sequence":"first","affiliation":[{"name":"Neuroscience Research Unit Saint\u2010Luc Hospital CRCHUM Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille","family":"B\u00e9langer","sequence":"additional","affiliation":[{"name":"Neuroscience Research Unit Saint\u2010Luc Hospital CRCHUM Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bich N.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of pathology Saint\u2010Luc Hospital CHUM Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger F.","family":"Butterworth","sequence":"additional","affiliation":[{"name":"Neuroscience Research Unit Saint\u2010Luc Hospital CRCHUM Montreal QC 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