Increased brain lactate is central to the development of brain edema in rats with chronic liver disease
dc.contributor.author | Bosoi, Cristina R. | |
dc.contributor.author | Zwingmann, Claudia | |
dc.contributor.author | Marin, Helen A. | |
dc.contributor.author | Parent-Robitaille, Christian | |
dc.contributor.author | Huynh, Jimmy | |
dc.contributor.author | Tremblay, Mélanie | |
dc.contributor.author | Rose, Christopher | |
dc.date.accessioned | 2015-03-05T18:29:21Z | |
dc.date.available | 2015-03-05T18:29:21Z | |
dc.date.issued | 2014 | |
dc.identifier.uri | http://hdl.handle.net/1866/11398 | |
dc.description.sponsorship | Canadian Institutes of Health Research. CB:Fonds de recherche du Québec – Santé | fr |
dc.subject | Chronic liver failure | fr |
dc.subject | Hepatic encephalopathy | fr |
dc.subject | Lactate | fr |
dc.subject | Nuclear magnetic resonance | fr |
dc.subject | Glutamine | fr |
dc.subject | Brain edema | fr |
dc.subject | Maladie du foie en phase terminale | fr |
dc.subject | Encéphalopathie hépatique | fr |
dc.subject | Acide lactique | fr |
dc.subject | Résonance magnétique nucléaire biomoléculaire | fr |
dc.subject | Oedème cérébral | fr |
dc.title | Increased brain lactate is central to the development of brain edema in rats with chronic liver disease | fr |
dc.type | Article | fr |
dc.contributor.affiliation | Université de Montréal. Faculté de médecine | fr |
dc.contributor.affiliation | Université de Montréal. Faculté de médecine. Centre de recherche du CHUM | fr |
dc.identifier.doi | 10.1016/j.jhep.2013.10.011 | |
dcterms.abstract | The pathogenesis of brain edema in patients with chronic liver disease (CLD) and minimal hepatic encephalopathy (HE) remains undefined. This study evaluated the role of brain lactate, glutamine and organic osmolytes, including myo-inositol and taurine, in the development of brain edema in a rat model of cirrhosis.Six-week bile-duct ligated (BDL) rats were injected with (13)C-glucose and de novo synthesis of lactate, and glutamine in the brain was quantified using (13)C nuclear magnetic resonance spectroscopy (NMR). Total brain lactate, glutamine, and osmolytes were measured using (1)H NMR or high performance liquid chromatography. To further define the interplay between lactate, glutamine and brain edema, BDL rats were treated with AST-120 (engineered activated carbon microspheres) and dichloroacetate (DCA: lactate synthesis inhibitor).Significant increases in de novo synthesis of lactate (1.6-fold, p<0.001) and glutamine (2.2-fold, p<0.01) were demonstrated in the brains of BDL rats vs. SHAM-operated controls. Moreover, a decrease in cerebral myo-inositol (p<0.001), with no change in taurine, was found in the presence of brain edema in BDL rats vs. controls. BDL rats treated with either AST-120 or DCA showed attenuation in brain edema and brain lactate. These two treatments did not lead to similar reductions in brain glutamine.Increased brain lactate, and not glutamine, is a primary player in the pathogenesis of brain edema in CLD. In addition, alterations in the osmoregulatory response may also be contributing factors. Our results suggest that inhibiting lactate synthesis is a new potential target for the treatment of HE. | fr |
dcterms.language | eng | fr |
UdeM.VersionRioxx | Version acceptée / Accepted Manuscript | |
oaire.citationTitle | Journal of hepatology | |
oaire.citationVolume | 60 | |
oaire.citationIssue | 3 | |
oaire.citationStartPage | 554 | |
oaire.citationEndPage | 560 |
Files in this item
This item appears in the following Collection(s)
This document disseminated on Papyrus is the exclusive property of the copyright holders and is protected by the Copyright Act (R.S.C. 1985, c. C-42). It may be used for fair dealing and non-commercial purposes, for private study or research, criticism and review as provided by law. For any other use, written authorization from the copyright holders is required.