Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: A PET study with [11C]acetate in humans

Frontiers in Neuroscience

Svend Borup Jensen¹  Peter eOtt²  Susanne eKeiding²  Hendrik eVilstrup²  Peter eIversen²  Michael eSørensen²  Kim eMouridsen³  Mikkel Bo Hansen³  Albert eGjedde⁴  Lasse Kristoffer eBak⁶  Helle S Waagepetersen⁶  Arne eSchousboe⁶ 

[1] Aalborg University Hospital;Aarhus University Hospital;Aarhus University;Johns Hopkins University;McGill University;University of Copenhagen, Faculty of Health and Medical Sciences;University of Copenhagen;

关键词: Astrocytes;    Mitochondria;    brain energy metabolism;    kinetic modelling;    Positron emission tomography.;   

DOI  :  10.3389/fnins.2014.00353

来源: DOAJ

【 摘 要 】

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 aremetabolized 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.

【 授权许可】

Unknown