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

Peter Iversen, Kim Mouridsen, Mikkel B. Hansen, Svend B. Jensen, Michael Sørensen, Lasse K. Bak, Helle S. Waagepetersen, Arne Schousboe, Peter Ott, Hendrik Vilstrup, Susanne Keiding, Albert Gjedde

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Abstract

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.

Original languageEnglish (US)
Article numberArticle 353
JournalFrontiers in Neuroscience
Volume8
Issue numberOCT
DOIs
StatePublished - Jan 1 2014

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Keywords

  • Astrocytes
  • Brain energy metabolism
  • Kinetic modelling
  • Mitochondria
  • Positron emission tomography

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Iversen, P., Mouridsen, K., Hansen, M. B., Jensen, S. B., Sørensen, M., Bak, L. K., Waagepetersen, H. S., Schousboe, A., Ott, P., Vilstrup, H., Keiding, S., & Gjedde, A. (2014). Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: A PET study with [11C]acetate in humans. Frontiers in Neuroscience, 8(OCT), [Article 353]. https://doi.org/10.3389/fnins.2014.00353