Stimulation-Induced Increases of Astrocytic Oxidative Metabolism in Rats and Humans Investigated with 1-11C-Acetate

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 ( k2) 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.