{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T21:29:42Z","timestamp":1780694982380,"version":"3.54.1"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2014,4,9]],"date-time":"2014-04-09T00:00:00Z","timestamp":1397001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Microglia and astrocyte related pro\u2010inflammatory responses are thought to underpin cerebral sequelae of acute liver failure. Conversely, despite background pro\u2010inflammatory responses in cirrhosis, overt brain swelling and coma associated with acute\u2010on\u2010chronic liver failure, is infrequent unless precipitated (e.g. sepsis). Moreover in other chronic neurodegenerative disorders and sepsis, the brain is protected from recurrent microbial insults by compensatory microglial\u2010associated immune responses. To characterise longitudinal cerebral immune responses in a bile duct\u2010ligated (BDL) rat model of cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Rats underwent BDL or sham operation before sacrifice at either 1\u2010day, 1, 2 and 4\u00a0weeks post\u2010surgery. We analysed consciousness, brain water, biochemistry and immunohistochemistry to assess activation of microglia (ED\u20101, OX6 and Iba\u20101), astrocytes (Glial fibrillary acidic protein \u2010 GFAP), cellular stress (Heat shock protein \u2010 Hsp 25) and pro\u2010inflammatory mediator expression (inducible nitric oxide synthase (iNOS), interleukin\u20101beta (IL\u20101\u03b2) and tumour growth factor\u2010beta (TGF\u2010\u03b2)).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BDL significantly increased ammonia and bilirubin (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01 respectively). The classical microglial markers OX6, ED1 and Iba\u20101 and pro\u2010inflammatory IL\u20101\u03b2 and iNOS were not significantly increased. However, the alternative microglial marker and regulatory cytokine TGF\u2010\u03b2 was elevated from day 1 to 4\u00a0weeks post\u2010BDL. GFAP expression was significantly increased in corpus callosum in all groups. In BDL rats, Hsp 25 was also increased in the corpus callosum, peaking at 2 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BDL triggers early alternative, but not classical, microglial activation. There was a correlation between astrocyte activation and cellular stress. These findings indicate early cerebral immune responses, which may be associated with immune tolerance to further challenge.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12481","type":"journal-article","created":{"date-parts":[[2014,2,17]],"date-time":"2014-02-17T11:27:07Z","timestamp":1392636427000},"page":"1184-1191","source":"Crossref","is-referenced-by-count":32,"title":["Characterisation of temporal microglia and astrocyte immune responses in bile duct\u2010ligated rat models of cirrhosis"],"prefix":"10.1111","volume":"34","author":[{"given":"Gavin A. K.","family":"Wright","sequence":"first","affiliation":[{"name":"Institute of Hepatology University College London Royal Free Hospital London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalda","family":"Sharifi","sequence":"additional","affiliation":[{"name":"Institute of Hepatology University College London Royal Free Hospital London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A.","family":"Newman","sequence":"additional","affiliation":[{"name":"Institute of Hepatology University College London Royal Free Hospital London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Davies","sequence":"additional","affiliation":[{"name":"Institute of Hepatology University College London Royal Free Hospital London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balasubramaniyam","family":"Vairappan","sequence":"additional","affiliation":[{"name":"Institute of Hepatology University College London Royal Free Hospital London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh V.","family":"Perry","sequence":"additional","affiliation":[{"name":"Institute of Hepatology University College London Royal Free Hospital London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Jalan","sequence":"additional","affiliation":[{"name":"Institute of Hepatology University College London Royal Free Hospital London London 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