Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: A PET study with [11C]acetate in humans
In patients with impaired liver function and hepatic encephalopathy (HE), consistent elevations of blood ammonia concentration suggest a crucial role in the pathogenesis of HE. Ammonia and acetate are metabolized in brain both primarily in astrocytes. Here, we used dynamic [11C]acetate PET of the b...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-11-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnins.2014.00353/full |
| _version_ | 1818313085134307328 |
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| author | Peter eIversen Kim eMouridsen Mikkel Bo Hansen Svend Borup Jensen Michael eSørensen Michael eSørensen Lasse Kristoffer eBak Helle S Waagepetersen Arne eSchousboe Peter eOtt Hendrik eVilstrup Susanne eKeiding Susanne eKeiding Susanne eKeiding Albert eGjedde Albert eGjedde Albert eGjedde Albert eGjedde |
| author_facet | Peter eIversen Kim eMouridsen Mikkel Bo Hansen Svend Borup Jensen Michael eSørensen Michael eSørensen Lasse Kristoffer eBak Helle S Waagepetersen Arne eSchousboe Peter eOtt Hendrik eVilstrup Susanne eKeiding Susanne eKeiding Susanne eKeiding Albert eGjedde Albert eGjedde Albert eGjedde Albert eGjedde |
| author_sort | Peter eIversen |
| collection | DOAJ |
| description | In patients with impaired liver function and hepatic encephalopathy (HE), consistent elevations of blood ammonia concentration suggest a crucial role in the pathogenesis of HE. Ammonia and acetate are metabolized in brain both primarily in astrocytes. Here, we used dynamic [11C]acetate PET of the brain to measure the contribution of astrocytes to the previously observed reduction of brain oxidative metabolism in patients with liver cirrhosis and HE, compared to patients with cirrhosis without HE, and to healthy subjects. We used a new kinetic model to estimate uptake from blood to astrocytes and astrocyte metabolism of [11C]acetate. No significant differences of the rate constant of oxidation of [11C]acetate (k3) were found among the three groups of subjects. The net metabolic clearance of [11C]acetate from blood was lower in the group of patients with cirrhosis and HE than in the group of healthy subjects (P<0.05), which we interpret to be an effect of reduced cerebral blood flow rather than a reflection of low [11C]acetate metabolism. We conclude that the characteristic decline of whole-brain oxidative metabolism in patients with cirrhosis with HE is not due to malfunction of oxidative metabolism in astrocytes. Thus, the observed decline of brain oxidative metabolism implicates changes of neurons and their energy turnover in patients with HE. |
| first_indexed | 2024-12-13T08:28:08Z |
| format | Article |
| id | doaj.art-c98f0db4866149fcb6964ae7f3a3ee20 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-13T08:28:08Z |
| publishDate | 2014-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-c98f0db4866149fcb6964ae7f3a3ee202022-12-21T23:53:50ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2014-11-01810.3389/fnins.2014.00353112438Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: A PET study with [11C]acetate in humansPeter eIversen0Kim eMouridsen1Mikkel Bo Hansen2Svend Borup Jensen3Michael eSørensen4Michael eSørensen5Lasse Kristoffer eBak6Helle S Waagepetersen7Arne eSchousboe8Peter eOtt9Hendrik eVilstrup10Susanne eKeiding11Susanne eKeiding12Susanne eKeiding13Albert eGjedde14Albert eGjedde15Albert eGjedde16Albert eGjedde17Aarhus University HospitalAarhus UniversityAarhus UniversityAalborg University HospitalAarhus University HospitalAarhus University HospitalUniversity of Copenhagen, Faculty of Health and Medical SciencesUniversity of Copenhagen, Faculty of Health and Medical SciencesUniversity of Copenhagen, Faculty of Health and Medical SciencesAarhus University HospitalAarhus University HospitalUniversity of CopenhagenAarhus University HospitalAarhus University HospitalUniversity of CopenhagenAarhus UniversityMcGill UniversityJohns Hopkins UniversityIn patients with impaired liver function and hepatic encephalopathy (HE), consistent elevations of blood ammonia concentration suggest a crucial role in the pathogenesis of HE. Ammonia and acetate are metabolized in brain both primarily in astrocytes. Here, we used dynamic [11C]acetate PET of the brain to measure the contribution of astrocytes to the previously observed reduction of brain oxidative metabolism in patients with liver cirrhosis and HE, compared to patients with cirrhosis without HE, and to healthy subjects. We used a new kinetic model to estimate uptake from blood to astrocytes and astrocyte metabolism of [11C]acetate. No significant differences of the rate constant of oxidation of [11C]acetate (k3) were found among the three groups of subjects. The net metabolic clearance of [11C]acetate from blood was lower in the group of patients with cirrhosis and HE than in the group of healthy subjects (P<0.05), which we interpret to be an effect of reduced cerebral blood flow rather than a reflection of low [11C]acetate metabolism. We conclude that the characteristic decline of whole-brain oxidative metabolism in patients with cirrhosis with HE is not due to malfunction of oxidative metabolism in astrocytes. Thus, the observed decline of brain oxidative metabolism implicates changes of neurons and their energy turnover in patients with HE.http://journal.frontiersin.org/Journal/10.3389/fnins.2014.00353/fullAstrocytesMitochondriabrain energy metabolismkinetic modellingPositron emission tomography. |
| spellingShingle | Peter eIversen Kim eMouridsen Mikkel Bo Hansen Svend Borup Jensen Michael eSørensen Michael eSørensen Lasse Kristoffer eBak Helle S Waagepetersen Arne eSchousboe Peter eOtt Hendrik eVilstrup Susanne eKeiding Susanne eKeiding Susanne eKeiding Albert eGjedde Albert eGjedde Albert eGjedde Albert eGjedde Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: A PET study with [11C]acetate in humans Frontiers in Neuroscience Astrocytes Mitochondria brain energy metabolism kinetic modelling Positron emission tomography. |
| title | Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: A PET study with [11C]acetate in humans |
| title_full | Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: A PET study with [11C]acetate in humans |
| title_fullStr | Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: A PET study with [11C]acetate in humans |
| title_full_unstemmed | Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: A PET study with [11C]acetate in humans |
| title_short | Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: A PET study with [11C]acetate in humans |
| title_sort | oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy a pet study with 11c acetate in humans |
| topic | Astrocytes Mitochondria brain energy metabolism kinetic modelling Positron emission tomography. |
| url | http://journal.frontiersin.org/Journal/10.3389/fnins.2014.00353/full |
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