Molecular Mechanisms of Neurological Alterations in Hepatic Encephalopathy

Abstract

Event Abstract Back to Event Molecular Mechanisms of Neurological Alterations in Hepatic Encephalopathy M. Llansola1*, O. Cauli1, P. Monfort1, A. Agustí1, H. Abrahach1, V. Retnikov1, V. Hernandez1, A. Cabrera1, A. González1, C. Giménez1 and V. Felipo1 1 Centro de Investigación Príncipe Felipe, Laboratory of Neurobiology, Spain Patients with liver diseases (e.g. cirrhosis) may present hepatic encephalopathy (HE), an alteration in cerebral function which is a consequence of failure of liver function. Patients with HE may present different neurological alterations, as impairment of cognitive or motor functions or altered sleep-wake cycle, which impairs their quality of live. Hyperammonemia is considered a main contributor to the neurological alterations in HE. Animal models of chronic HE (e.g. rats with portacaval shunts) or of ‘‘pure’’ hyperammonemia reproduce some of these impaired cerebral functions. Both hyperammonemia and neuroinflammation contribute to the impairment of cognitive and motor functions. We have found a good correlation between the learning ability and the function of the glutamate-nitric oxide-cGMP pathway in rat cerebellum in vivo. Treatment of rats with chronic HE or hyperammonemia by means of inhibitors of phosphodiesterase 5 (that increase levels of cGMP) restores the function of the glutamate-nitric oxide-cGMP pathway in cerebellum as well as the learning ability. The same beneficial effects may be obtained by treating the rats chronically with an anti-inflammatory compound, ibuprofen. Ibuprofen also improves the hypokinesia in rats with portacaval shunts. Hyperammonemic rats also show altered circadian rhythms of activity due to the impairment of the circadian variation of the hypothalamus-pituitary-adrenal axis. Mechanisms involved in the effects of hyperammonemia and inflammation include alteration in glutamatergic and GABAergic neurotransmission in cerebellum and basal ganglia. The study of these mechanisms in animal models of HE will allow the development of new and more efficient therapeutic strategies: for example, the increase of cGMP levels or anti-inflammatory molecules to improve learning and memory performance in individuals with HE. Conference: 2nd NEUROMED Workshop, Fez, Morocco, 10 Jun - 12 Jun, 2010. Presentation Type: Oral Presentation Topic: Oral Session 1: Brain diseases and their treatment Citation: Llansola M, Cauli O, Monfort P, Agustí A, Abrahach H, Retnikov V, Hernandez V, Cabrera A, González A, Giménez C and Felipo V (2010). Molecular Mechanisms of Neurological Alterations in Hepatic Encephalopathy. Front. Neurosci. Conference Abstract: 2nd NEUROMED Workshop. doi: 10.3389/conf.fnins.2010.12.00017 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 03 Jun 2010; Published Online: 03 Jun 2010. * Correspondence: M. Llansola, Centro de Investigación Príncipe Felipe, Laboratory of Neurobiology, Valencia, Spain, marta@cipf.es Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers M. Llansola O. Cauli P. Monfort A. Agustí H. Abrahach V. Retnikov V. Hernandez A. Cabrera A. González C. Giménez V. Felipo Google M. Llansola O. Cauli P. Monfort A. Agustí H. Abrahach V. Retnikov V. Hernandez A. Cabrera A. González C. Giménez V. Felipo Google Scholar M. Llansola O. Cauli P. Monfort A. Agustí H. Abrahach V. Retnikov V. Hernandez A. Cabrera A. González C. Giménez V. Felipo PubMed M. Llansola O. Cauli P. Monfort A. Agustí H. Abrahach V. Retnikov V. Hernandez A. Cabrera A. González C. Giménez V. Felipo Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.