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The aims were to test whether treatment with the ammonia\u2010lowering agent ornithine phenylacetate (<jats:styled-content style=\"fixed-case\">OP<\/jats:styled-content>) and\/or anti\u2010<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 (infliximab) prevent the deleterious brain consequences of lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>) in cirrhotic rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Rats 4\u00a0weeks following bile duct\u2010ligation (<jats:styled-content style=\"fixed-case\">BDL<\/jats:styled-content>), sham\u2010operation (sham) and\/or 7\u00a0days hyperammonemic feed (<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>), were randomized to receive <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> (1\u00a0mg\/kg) or saline, and treatment with either 3\u00a0days intraperitoneal injections of <jats:styled-content style=\"fixed-case\">OP<\/jats:styled-content> (0.6\u00a0g\/kg) and\/or infliximab, 10\u00a0mg\/kg. Animals were sacrificed at coma stages or at 3\u00a0h.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In sham rats, both HD and LPS increased brain water, with an increase in ammonia in the former and brain cytokines in the latter but with no effect on consciousness. BDL\u00a0+\u00a0HD rats caused significantly higher plasma ammonia, TNF\u2010\u03b1 and IL\u20106 levels compared to sham. LPS significantly worsened coma stage, increased brain water and plasma and brain TNF\u2010\u03b1. OP significantly delayed LPS\u2010induced progression to coma stages (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.009), reduced arterial ammonia and brain water (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 and <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01 respectively), which was associated with a significant reduction in cytokines. Infliximab significantly reduced plasma and brain cytokines, but not brain water. OP\u00a0+\u00a0infliximab attenuated increase in brain water and delayed occurrence of coma, which was not different to OP alone. In BDL rats, OP reduced the expression of brain <jats:styled-content style=\"fixed-case\">iNOS<\/jats:styled-content> and NF\u03baB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Reduction in ammonia with OP in cirrhotic rats prevents LPS\u2010induced brain edema and delays coma, suggesting that ammonia may prime the brain to the deleterious effect of LPS, possibly through effects on <jats:styled-content style=\"fixed-case\">iNOS<\/jats:styled-content> and NF\u03baB related mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1478-3231.2011.02698.x","type":"journal-article","created":{"date-parts":[[2011,12,8]],"date-time":"2011-12-08T05:54:04Z","timestamp":1323323644000},"page":"410-419","source":"Crossref","is-referenced-by-count":39,"title":["Reduction in hyperammonaemia by ornithine phenylacetate prevents lipopolysaccharide\u2010induced brain edema and coma in cirrhotic 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