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


Wyss, M T; Weber, B; Treyer, V; Heer, S; Pellerin, L; Magistretti, P J; Buck, A (2009). Stimulation-induced increases of astrocytic oxidative metabolism in rats and humans investigated with 1-11C-acetate. Journal of Cerebral Blood Flow and Metabolism, 29(1):44-56.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nuclear Medicine
04 Faculty of Medicine > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2009
Deposited On:12 Mar 2009 12:32
Last Modified:05 Apr 2016 12:57
Publisher:Nature Publishing Group
ISSN:0271-678X
Additional Information:Nature Publishing Group - Full text article
Publisher DOI:10.1038/jcbfm.2008.86
Official URL:http://www.nature.com/jcbfm/journal/v29/n1/pdf/jcbfm200886a.pdf
PubMed ID:18714330
Permanent URL: http://doi.org/10.5167/uzh-12514

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