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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Wyss M. T., Weber B., Treyer V., Heer S., Pellerin L., Magistretti P. J., Buck A.,
Project A multimodal approach to cerebral blood flow and metabolism
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Original article (peer-reviewed)

Journal J Cereb Blood Flow Metab
Volume (Issue) 29
Page(s) 44 - 56
Title of proceedings J Cereb Blood Flow Metab

Abstract

The purpose of this study was to investigate astrocytic oxidative metabolism using 1-(11)C-acetate. 1-(11)C-acetate kinetics were evaluated in the rat somatosensory cortex using a beta-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 (11)C-CO(2) and therefore related to oxygen consumption (CMRO(2)): (1) the onset of (11)C washout was delayed; (2) k(2) was not affected by acetazolamide-induced blood flow increase; (3) k(2) 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 k(2). In the test-retest experiments K(1) and k(2) were very stable. In summary, 1-(11)C-acetate seems a promising tracer to investigate astrocytic oxidative metabolism in vivo. If the washout rate indeed represents the production of (11)C-CO(2), then its increase during stimulation would point to a substantially higher astrocytic oxidative metabolism during brain activation. However, the quantitative relationship between k(2) and CMRO(2) needs to be determined in future experiments.Journal of Cerebral Blood Flow & Metabolism advance online publication, 20 August 2008; doi:10.1038/jcbfm.2008.86.
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