Oxidative glucose metabolism in rat brain during single forepaw stimulation: A spatially localized H-1[C-13] nuclear magnetic resonance study

In the alpha-chloralose-anesthetized rat during single forepaw stimulation, a spatially localized H-1[C-13] nuclear magnetic resonance spectroscopic method was used to measure the rate of cerebral [C4]-glutamate isotopic turnover from infused [1,6-C-13]glucose. The glutamate turnover data were analyzed using a mathematical model of cerebral glucose metabolism to evaluate the tricarboxylic add (TCA) cycle flux (V-TCA). During stimulation the value of V-TCA in the sensorimotor region increased from 0.47 +/- 0.06 (at rest) to 1.44 +/- 0.41 mu mol.g(-1).min(-1) (P < 0.01) in the contralateral hemispheric compartment (24 mm(3)) and to 0.65 +/- 0.10 mu mol.g(-1).min(-1) (P < 0.03) in the ipsilateral side. Each V-TCA 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 mu mol.g(-1).min(-1); current study) is in the range total-CMRglc previously reported for awake rats undergoing physiologic activation (0.7-1.4 mu mol.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.