nach oben

Metabolic Brain Disease

Erschienen in:

09.08.2015 | Original Article

¹H and ³¹P magnetic resonance spectroscopy in a rat model of chronic hepatic encephalopathy: in vivo longitudinal measurements of brain energy metabolism

verfasst von: Veronika Rackayova, Olivier Braissant, Valérie A. McLin, Corina Berset, Bernard Lanz, Cristina Cudalbu

Erschienen in: Metabolic Brain Disease | Ausgabe 6/2016

Einloggen, um Zugang zu erhalten

Abstract

Chronic liver disease (CLD) leads to a spectrum of neuropsychiatric disorders named hepatic encephalopathy (HE). Even though brain energy metabolism is believed to be altered in chronic HE, few studies have explored energy metabolism in CLD-induced HE, and their findings were inconsistent. The aim of this study was to characterize for the first time in vivo and longitudinally brain metabolic changes in a rat model of CLD-induced HE with a focus on energy metabolism, using the methodological advantages of high field proton and phosphorus Magnetic Resonance Spectroscopy (¹H- and ³¹P-MRS). Wistar rats were bile duct ligated (BDL) and studied before BDL and at post-operative weeks 4 and 8. Glutamine increased linearly over time (+146 %) together with plasma ammonium (+159 %). As a compensatory effect, other brain osmolytes decreased: myo-inositol (-36 %), followed by total choline and creatine. A decrease in the neurotransmitters glutamate (-17 %) and aspartate (-28 %) was measured only at week 8, while no significant changes were observed for lactate and phosphocreatine. Among the other energy metabolites measured by ³¹P-MRS, we observed a non-significant decrease in ATP together with a significant decrease in ADP (-28 %), but only at week 8 after ligation. Finally, brain glutamine showed the strongest correlations with changes in other brain metabolites, indicating its importance in type C HE. In conclusion, mild alterations in some metabolites involved in energy metabolism were observed but only at the end stage of the disease when edema and neurological changes are already present. Therefore, our data indicate that impaired energy metabolism is not one of the major causes of early HE symptoms in the established model of type C HE.

Nur mit Berechtigung zugänglich

Barbiroli B, Gaiani S, Lodi R et al (2002) Abnormal brain energy metabolism shown by in vivo phosphorus magnetic resonance spectroscopy in patients with chronic liver disease. Brain Res Bull 59:75–82. doi:10.1016/S0361-9230(02)00839-0 CrossRefPubMed

Biecker E, De Gottardi A, Neef M et al (2005) Long-term treatment of bile duct-ligated rats with rapamycin (sirolimus) significantly attenuates liver fibrosis: analysis of the underlying mechanisms. J Pharmacol Exp Ther 313:952–961. doi:10.1124/jpet.104.079616 CrossRefPubMed

Blei AT, Córdoba J (2001) Hepatic encephalopathy. Am J Gastroenterol 96:1968–1976. doi:10.1111/j.1572-0241.2001.03964.x CrossRefPubMed

Bluml S, Zuckerman E, Tan J, Ross BD (1998) Proton-decoupled 31P magnetic resonance spectroscopy reveals osmotic and metabolic disturbances in human hepatic encephalopathy. J Neurochem 71:1564–1576CrossRefPubMed

Bosoi CR, Parent-Robitaille C, Anderson K et al (2011) AST-120 (spherical carbon adsorbent) lowers ammonia levels and attenuates brain edema in bile duct-ligated rats. Hepatology 53:1995–2002. doi:10.1002/hep.24273 CrossRefPubMed

Bosoi CR, Zwingmann C, Marin H et al (2014) Increased brain lactate is central to the development of brain edema in rats with chronic liver disease. J Hepatol 60:554–560. doi:10.1016/j.jhep.2013.10.011 CrossRefPubMed

Bothwell JH, Styles P, Bhakoo KK (2002) Swelling-activated taurine and creatine effluxes from rat cortical astrocytes are pharmacologically distinct. J Membr Biol 185:157–164. doi:10.1007/s00232-001-0121-2 CrossRefPubMed

Braissant O (2010) Ammonia toxicity to the brain: effects on creatine metabolism and transport and protective roles of creatine. Mol Genet Metab 100(Suppl):S53–8. doi:10.1016/j.ymgme.2010.02.011 PubMed

Braissant O, Henry H, Villard A-M et al (2002) Ammonium-induced impairment of axonal growth is prevented through glial creatine. J Neurosci 22:9810–9820PubMed

Braissant O, McLin VA, Cudalbu C (2013) Ammonia toxicity to the brain. J Inherit Metab Dis 36:595–612. doi:10.1007/s10545-012-9546-2 CrossRefPubMed

Brusilow SW, Traystman R (1986) Hepatic encephalopathy. N Engl J Med 314:786–787, author reply 787 PubMed

Brusilow SW, Koehler RC, Traystman RJ, Cooper AJL (2010) Astrocyte glutamine synthetase: importance in hyperammonemic syndromes and potential target for therapy. Neurotherapeutics 7:452–470. doi:10.1016/j.nurt.2010.05.015 CrossRefPubMedPubMedCentral

Butterworth RF (2003) Pathogenesis of hepatic encephalopathy: new insights from neuroimaging and molecular studies. J Hepatol 39:278–285. doi:10.1016/S0168-8278(03)00267-8 CrossRefPubMed

Butterworth RF, Norenberg MD, Felipo V et al (2009) Experimental models of hepatic encephalopathy: ISHEN guidelines. Liver Int 29:783–788. doi:10.1111/j.1478-3231.2009.02034.x CrossRefPubMed

Chavarria L, Oria M, Romero-Gimenez J et al (2010) Diffusion tensor imaging supports the cytotoxic origin of brain edema in a rat model of acute liver failure. Gastroenterology 138:1566–1573. doi:10.1053/j.gastro.2009.10.003 CrossRefPubMed

Chavarria L, Oria M, Romero-Giménez J et al (2013) Brain magnetic resonance in experimental acute-on-chronic liver failure. Liver Int 33:294–300. doi:10.1111/liv.12032 CrossRefPubMed

Cooper JLA, Plum F (1987) Biochemistry and physiology of brain ammonia. Physiol Rev 67:440–519PubMed

Córdoba J, Alonso J, Rovira A et al (2001) The development of low-grade cerebral edema in cirrhosis is supported by the evolution of (1)H-magnetic resonance abnormalities after liver transplantation. J Hepatol 35:598–604CrossRefPubMed

Cudalbu C (2013) In vivo studies of brain metabolism in animal models of Hepatic Encephalopathy using ¹H Magnetic Resonance Spectroscopy. Metab Brain Dis 28:167–174. doi:10.1007/s11011-012-9368-9 CrossRefPubMed

Cudalbu C, Mlynárik V, Gruetter R (2012) Handling macromolecule signals in the quantification of the neurochemical profile. J Alzheimers Dis 31(Suppl 3):S101–S115. doi:10.3233/JAD-2012-120100 PubMed

Cudalbu C, Rackayova V, McLin VA, Braissant O (2014) Brain Glutamine, Osmolytes and Edema in a Model of Chronic Hepatic Encephalopathy: in vivo and Londitudinal Measurements using 1H MRS, DTI and Immunofluorescence. 16th ISHEN Meet London. doi: 10.1002/yea.122

Dam G, Keiding S, Munk OL et al (2013) Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake. Hepatology 57:258–265. doi:10.1002/hep.25995 CrossRefPubMed

Davies NA, Wright G, Ytrebø LM et al (2009) L-ornithine and phenylacetate synergistically produce sustained reduction in ammonia and brain water in cirrhotic rats. Hepatology 50:155–164. doi:10.1002/hep.22897 CrossRefPubMed

Felipo V, Butterworth RF (2002) Neurobiology of ammonia. Prog Neurobiol 67:259–279CrossRefPubMed

Ferenci P, Lockwood A, Mullen K et al (2002) Hepatic encephalopathy--definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology 35:716–721. doi:10.1053/jhep.2002.31250 CrossRefPubMed

Flögel U, Niendorf T, Serkowa N et al (1995) Changes in organic solutes, volume, energy state, and metabolism associated with osmotic stress in a glial cell line: a multinuclear NMR study. Neurochem Res 20:793–802CrossRefPubMed

Golding EM, Teague WE, Dobson GP (1995) Adjustment of K’ to varying pH and pMg for the creatine kinase, adenylate kinase and ATP hydrolysis equilibria permitting quantitative bioenergetic assessment. J Exp Biol 198:1775–1782PubMed

Gruetter R, Tkác I (2000) Field mapping without reference scan using asymmetric echo-planar techniques. Magn Reson Med 43:319–323CrossRefPubMed

Häussinger D (2006) Low grade cerebral edema and the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology 43:1187–1190. doi:10.1002/hep.21235 CrossRefPubMed

Häussinger D, Kircheis G, Fischer R et al (2000) Hepatic encephalopathy in chronic liver disease: a clinical manifestation of astrocyte swelling and low-grade cerebral edema? J Hepatol 32:1035–1038CrossRefPubMed

Hazell AS, Butterworth RF (1999) Hepatic encephalopathy: an update of pathophysiologic mechanisms. Proc Soc Exp Biol Med 222:99–112CrossRefPubMed

Iotti S, Frassineti C, Alderighi L et al (1996) In vivo assessment of free magnesium concentration in human brain by 31P MRS. A new calibration curve based on a mathematical algorithm. NMR Biomed 9:24–32. doi:10.1002/(SICI)1099-1492(199602)9:1<24::AID-NBM392>3.0.CO;2-B CrossRefPubMed

Kale RA, Gupta RK, Saraswat VA et al (2006) Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy. Hepatology 43:698–706. doi:10.1002/hep.21114 CrossRefPubMed

Kosenko E, Kaminsky Y, Grau E et al (1994) Brain ATP depletion induced by acute ammonia intoxication in rats is mediated by activation of the NMDA receptor and Na+, K+ ATPase. J Neurochem 63:2172–2178CrossRefPubMed

Kreis R, Farrow N, Ross BD (1991) Localized 1H NMR spectroscopy in patients with chronic hepatic encephalopathy. Analysis of changes in cerebral glutamine, choline and inositols. NMR Biomed 4:109–116CrossRefPubMed

Kreis R, Ross BD, Farrow NA, Ackerman Z (1992) Metabolic disorders of the brain in chronic hepatic encephalopathy detected with H-1 MR spectroscopy. Radiology 182:19–27. doi:10.1148/radiology.182.1.1345760 CrossRefPubMed

Kuby SA, Noda L, Lardy HA (1954) Adenosinetriphosphate-creatine transphosphorylase. J Biol Chem 210:65–82PubMed

Lai JC, Cooper AJ (1991) Neurotoxicity of ammonia and fatty-acids - differential inhibition of mitochondrial dehydrogenases by ammonia and fatty acyl coenzyme a derivatives. Neurochem Res 16:795–803CrossRefPubMed

Lanz B, Cudalbu C, Mclin V, et al. (2014) Effects of chronic hepatic encephalopathy on brain energy metabolism , studied by in vivo 13 C MRS in rats. 16th ISHEN Meet. London. pp 1–2

Lavoie J, Giguère JF, Layrargues GP, Butterworth RF (1987) Amino acid changes in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. J Neurochem 49:692–697CrossRefPubMed

Leke R, Bak LK, Iversen P et al (2011) Synthesis of neurotransmitter GABA via the neuronal tricarboxylic acid cycle is elevated in rats with liver cirrhosis consistent with a high GABAergic tone in chronic hepatic encephalopathy. J Neurochem 117:824–832. doi:10.1111/j.1471-4159.2011.07244.x CrossRefPubMed

Leke R, de Oliveira DL, Mussulini BHM et al (2012) Impairment of the organization of locomotor and exploratory behaviors in bile duct-ligated rats. PLoS One 7, e36322. doi:10.1371/journal.pone.0036322 CrossRefPubMedPubMedCentral

Lien YHH, Shapiro JI, Chan L (1990) Effects of hypernatremia on organic brain osmoles. J Clin Invest 85:1427–1435. doi:10.1172/JCI114587 CrossRefPubMedPubMedCentral

Lockwood AH, Ginsberg MD, Rhoades HM, Gutierrez MT (1986) Cerebral glucose metabolism after portacaval shunting in the rat. Patterns of metabolism and implications for the pathogenesis of hepatic encephalopathy. J Clin Invest 78:86–95. doi:10.1172/JCI112578 CrossRefPubMedPubMedCentral

McPhail MJW, Patel NR, Taylor-Robinson SD (2012) Brain Imaging and hepatic encephalopathy. Clin Liver Dis 16:57–72. doi:10.1016/j.cld.2011.12.001 CrossRefPubMed

Mlynárik V, Gambarota G, Frenkel H, Gruetter R (2006) Localized short-echo-time proton MR spectroscopy with full signal-intensity acquisition. Magn Reson Med 56:965–970. doi:10.1002/mrm.21043 CrossRefPubMed

Mlynárik V, Cacquevel M, Sun-Reimer L et al (2012) Proton and phosphorus magnetic resonance spectroscopy of a mouse model of Alzheimer’s disease. J Alzheimers Dis 31(Suppl 3):S87–S99. doi:10.3233/JAD-2012-112072 PubMed

Nioka S, Chance B, Hilberman M et al (1987) Relationship between intracellular pH and energy metabolism in dog brain as measured by 31P-NMR. J Appl Physiol 62:2094–2102PubMed

Ott P, Vilstrup H (2014) Cerebral effects of ammonia in liver disease: current hypotheses. Metab Brain Dis 29:901–911. doi:10.1007/s11011-014-9494-7 CrossRefPubMed

Ott P, Clemmesen O, Larsen FS (2005) Cerebral metabolic disturbances in the brain during acute liver failure: From hyperammonemia to energy failure and proteolysis. Neurochem Int 47:13–18. doi:10.1016/j.neuint.2005.04.002 CrossRefPubMed

Petroff O, Prichard J (1985) Cerebral intracellular pH by 31P nuclear magnetic resonance. Neurology 35:781–788CrossRefPubMed

Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed 14:260–264. doi:10.1002/nbm.698 CrossRefPubMed

Quinn M, McMillin M, Galindo C et al (2014) Bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanisms. Dig Liver Dis 46:527–534. doi:10.1016/j.dld.2014.01.159 CrossRefPubMedPubMedCentral

Rackayova V, Lanz B, Berset C, et al. (2015) In vivo Longitudinal Measurements of Brain Energy Metabolism in Chronic Hepatic Encephalopathy in a Rat Model using 31P MRS and 1H MRS. 23rd Annu. ISMRM Meet. Toronto. p 1

Rae CD (2014) A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra. Neurochem Res 39:1–36. doi:10.1007/s11064-013-1199-5 CrossRefPubMed

Rama Rao KV, Norenberg MD (2012) Brain energy metabolism and mitochondrial dysfunction in acute and chronic hepatic encephalopathy. Neurochem Int 60:697–706. doi:10.1016/j.neuint.2011.09.007 CrossRefPubMed

Rao KVR, Norenberg MD (2001) Cerebral energy metabolism in hepatic encephalopathy and hyperammonemia. Metab Brain Dis 16:67–78. doi:10.1023/A:1011666612822 CrossRefPubMed

Ratnakumari L, Audet R, Qureshi IA, Butterworth RF (1995) Na+, K+−ATPase activities are increased in brain in both congenital and acquired hyperammonemic syndromes. Neurosci Lett 197:89–92CrossRefPubMed

Schousboe A, Waagepetersen HS, Leke R, Bak LK (2014) Effects of hyperammonemia on brain energy metabolism: controversial findings in vivo and in vitro. Metab Brain Dis. doi:10.1007/s11011-014-9513-8

Shah NJ, Neeb H, Kircheis G et al (2008) Quantitative cerebral water content mapping in hepatic encephalopathy. Neuroimage 41:706–717. doi:10.1016/j.neuroimage.2008.02.057 CrossRefPubMed

Taylor-Robinson SD, Sargentoni J, Oatridge A et al (1996) MR imaging and spectroscopy of the basal ganglia in chronic liver disease: correlation of T1-weighted contrast measurements with abnormalities in proton and phosphorus-31 MR spectra. Metab Brain Dis 11:249–268CrossRefPubMed

Taylor-Robinson SD, Buckley C, Changani KK et al (1999) Cerebral proton and phosphorus-31 magnetic resonance spectroscopy in patients with subclinical hepatic encephalopathy. Liver 19:389–398. doi:10.1111/j.1478-3231.1999.tb00067.x CrossRefPubMed

Tkáč I, Starčuk Z, Choi IY, Gruetter R (1999) In vivo 1H NMR spectroscopy of rat brain at 1 ms echo time. Magn Reson Med 41:649–656. doi:10.1002/(SICI)1522-2594(199904)41:4<649::AID-MRM2>3.0.CO;2-G CrossRefPubMed

Tkac I, Henry P-G, Zacharoff L et al (2012) Homeostatic adaptations in brain energy metabolism in mouse models of Huntington disease. J Cereb Blood Flow Metab 32:1977–1988. doi:10.1038/jcbfm.2012.104 CrossRefPubMedPubMedCentral

Vanhamme L, van den Boogaart A, Van Huffel S (1997) Improved method for accurate and efficient quantification of MRS data with use of prior knowledge. J Magn Reson 129:35–43CrossRefPubMed

Veech RL, Lawson JW, Cornell NW, Krebs HA (1979) Cytosolic phosphorylation potential. J Biol Chem 254:6538–6547PubMed

Zwingmann C (2007) The anaplerotic flux and ammonia detoxification in hepatic encephalopathy. Metab Brain Dis 22:235–249. doi:10.1007/s11011-007-9069-y CrossRefPubMed

Zwingmann C, Butterworth R (2005) An update on the role of brain glutamine synthesis and its relation to cell-specific energy metabolism in the hyperammonemic brain: further studies using NMR spectroscopy. Neurochem Int 47:19–30. doi:10.1016/j.neuint.2005.04.003 CrossRefPubMed

Titel: 1H and 31P magnetic resonance spectroscopy in a rat model of chronic hepatic encephalopathy: in vivo longitudinal measurements of brain energy metabolism
verfasst von: Veronika Rackayova
Olivier Braissant
Valérie A. McLin
Corina Berset
Bernard Lanz
Cristina Cudalbu
Publikationsdatum: 09.08.2015
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 6/2016
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-015-9715-8

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Vierten reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Bluttest erkennt Parkinson schon zehn Jahre vor der Diagnose

10.05.2024 Parkinson-Krankheit Nachrichten

Ein Bluttest kann abnorm aggregiertes Alpha-Synuclein bei einigen Menschen schon zehn Jahre vor Beginn der motorischen Parkinsonsymptome nachweisen. Mit einem solchen Test lassen sich möglicherweise Prodromalstadien erfassen und die Betroffenen früher behandeln.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Wartezeit nicht kürzer, aber Arbeit flexibler

Psychotherapie Medizin aktuell

Fünf Jahren nach der Neugestaltung der Psychotherapie-Richtlinie wurden jetzt die Effekte der vorgenommenen Änderungen ausgewertet. Das Hauptziel der Novellierung war eine kürzere Wartezeit auf Therapieplätze. Dieses Ziel wurde nicht erreicht, es gab jedoch positive Auswirkungen auf andere Bereiche.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2016

Altered urinary porphyrins and mercury exposure as biomarkers for autism severity in Egyptian children with autism spectrum disorder

Timosaponin B-II ameliorates scopolamine-induced cognition deficits by attenuating acetylcholinesterase activity and brain oxidative damage in mice

Probiotics in management of hepatic encephalopathy

Altered expression and localization of synaptophysin in developing cerebellar cortex of neonatal rats due to maternal diabetes mellitus

Delayed bradykinin postconditioning modulates intrinsic neuroprotective enzyme expression in the rat CA1 region after cerebral ischemia: a proteomic study