Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 29, Issue 1, Pages 44-56Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/jcbfm.2008.86
Keywords
1-C-11-acetate; astrocytes; beta-scintillator; oxidative metabolism; positron emission tomography; washout
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Funding
- Swiss National Science Foundation [3100A0-105804/1, PP00B-110751/1]
- OPO-Stiftung Zurich
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The purpose of this study was to investigate astrocytic oxidative metabolism using 1-C-11-acetate. 1-C-11-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 C-11-CO2 and therefore related to oxygen consumption (CMRO2): (1) the onset of C-11 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-C-11-acetate seems a promising tracer to investigate astrocytic oxidative metabolism in vivo. If the washout rate indeed represents the production of C-11-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.
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