Oxidative Glucose Metabolism in Rat Brain during Single Forepaw Stimulation: A Spatially Localized 1H[13C] Nuclear Magnetic Resonance Study

Abstract

In the α-chloralose-anesthetized rat during single forepaw stimulation, a spatially localized 1H[13C] nuclear magnetic resonance spectroscopic method was used to measure the rate of cerebral [C4]-glutamate isotopic turnover from infused [1,6-13C]glucose. The glutamate turnover data were analyzed using a mathematical model of cerebral glucose metabolism to evaluate the tricarboxylic acid (TCA) cycle flux (VTCA). During stimulation the value of VTCA in the sensorimotor region increased from 0.47 ± 0.06 (at rest) to 1.44 ± 0.41 μmol·g−1 min−1 ( P < 0.01) in the contralateral hemispheric compartment (24 mm3) and to 0.65 ± 0.10 μmol·g−1min−1 ( P < 0.03) in the ipsilateral side. Each VTCA value was converted to the cerebral metabolic rates of glucose oxidation ( oxidative-CMRglC) and oxygen consumption (CMRO2). These rates were corrected for partial-volume based on activation maps obtained by blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI). The percent increase and the absolute value of oxidative-CMRglc in the activated regions are similar to values reported previously for total-CMRglc using the same activation paradigm. This indicates that the large majority of energy required for brain activation, in going from the resting to an activated state, is supplied by glucose oxidation. The level of activity during stimulation is relevant to awake animals because the oxidative-CMRglc (1.05 ± 0.28 μmol·g−1·min−1; current study) is in the range of total-CMRglc previously reported for awake rats undergoing physiologic activation (0.7–1.4 μmol·g−1 min−1). It is concluded that oxidative glycolysis is the main source of energy for increased brain activity and a positive BOLD fMRI signal-change occurs in conjunction with a large increase in CMRO2.