Stimulation-induced increases of astrocytic oxidative metabolism in rats and humans investigated with 1-11C-acetate

Matthias T. Wyss, Bruno Weber, Valerie Treyer, Stefan Heer, Luc Pellerin, Pierre Magistretti, Alfred Buck*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The purpose of this study was to investigate astrocytic oxidative metabolism using 1-11C-acetate. 1-11C-acetate kinetics were evaluated in the rat somatosensory cortex using a β-scintillator during different manipulations (test-retest, infraorbital nerve stimulation, and administration of acetazolamide or dichloroacetate). In humans a visual activation paradigm was used and kinetics were measured with positron emission tomography. Data were analyzed using a one-tissue compartment model. The following features supported the hypothesis that washout of radiolabel (k 2) is because of 11C-CO2 and therefore related to oxygen consumption (CMRO2): (1) the onset of 11C washout was delayed; (2) k2 was not affected by acetazolamide-induced blood flow increase; (3) k2 demonstrated a significant increase during stimulation in rats (from 0.014±0.007 to 0.027±0.006 per minute) and humans (from 0.016±0.010 to 0.026±0.006 per minute); and (4) dichloroacetate led to a substantial decrease of k2. In the test-retest experiments K1 and k2 were very stable. In summary, 1-11C-acetate seems a promising tracer to investigate astrocytic oxidative metabolism in vivo. If the washout rate indeed represents the production of 11C-CO2, then its increase during stimulation would point to a substantially higher astrocytic oxidative metabolism during brain activation. However, the quantitative relationship between k2 and CMRO2 needs to be determined in future experiments.

Original languageEnglish (US)
Pages (from-to)44-56
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • 1-C-acetate
  • Astrocytes
  • Oxidative metabolism
  • Positron emission tomography
  • Washout
  • β-scintillator

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'Stimulation-induced increases of astrocytic oxidative metabolism in rats and humans investigated with 1-<sup>11</sup>C-acetate'. Together they form a unique fingerprint.

Cite this