What we know: the inflammatory basis of hepatic encephalopathy.
Central Nervous System (CNS) degeneration appearing in patients with cirrhosis is responsible for cognitive and persistent motor impairments that lead to an important impact on life quality. Brain injury affects certain areas of the CNS that might affect two types of cells: neurons and astrocytes. The process leading to brain injury could be induced by portosystemic shunting accompanied by hyperammonemia and by the activation of peripheral inflammation, manifested as episodic encephalopathy. Hyperammonemia combined with a decrease on the BCA/AAA ratio induces alterations of energetic metabolism and the formation of free radicals in the CNS. This process would be stimulated by the activation of peripheral inflammatory mediators that could act on receptors of the blood brain barrier such as TLR4, activating inflammatory responses in the CNS. As a result, a persistent activation of microglia and an irreversible neuronal and astrocytic injury would be induced. A new knowledge of the mechanisms leading to brain injury in cirrhosis would develop protective strategies to correct changes of nitrogen metabolism and inflammation.
Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5 Str, 02-106, Warsaw, Poland.
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Translational Research in Fetal Surgery for Congenital Malformations, Center for Fetal, Cellular and Molecular Therapy, Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center (CCHMC), 3333 Burnet Avenue, MLC 11020, S 8.400 AT, Cincinnati, OH, 45229-3039, USA. Marc.Oria@cchmc.org.|Liver Failure Group, UCL Institute for Liver and Digestive Health, Royal Free Hospital, University College London, London, UK. Marc.Oria@cchmc.org.
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D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D018836:Inflammation Mediators / Q000378:metabolism*
D018836:Inflammation Mediators
Astrocytes; Hepatic encephalopathy; Inflammation; Microglia; Neurodegeneration