Shulman R G, Rothman D L, Hyder F
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06510, USA.
Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3245-50. doi: 10.1073/pnas.96.6.3245.
Focal changes in the cerebral metabolic rate of glucose utilization (CMRglc) are small (10-40%) during sensory activation in awake humans, as well as in awake rodents and primates (20-50%). They are significantly larger (50-250%) in sensory activation studies of anesthetized rats and cats. Our data, in agreement with literature values, show that in the resting anesthetized state values of CMRglc are lower than in the resting nonanesthetized state whereas the final state values, reached upon activation, are similar for the anesthetized and nonanesthetized animals. The lower resting anesthetized state values of CMRglc explain why the increments upon activation from anesthesia are larger than when starting from the nonanesthetized conditions. Recent 13C NMR measurements in our laboratory have established a quantitative relationship between the energetics of glucose oxidation, CMRglc (oxidative), and the flux of the glutamate/gamma-aminobutyric acid/glutamine neurotransmitter cycle, Vcycle. In both the resting awake value of CMRglc(oxidative), and its increment upon stimulation, a large majority (approximately 80%) of the brain energy consumption is devoted to Vcycle. In the differencing methods of functional imaging, it is assumed that the incremental change in the measured signal represents the modular activity that supports the functional response. However, the same amount of activity must be present during the response to stimulation, irrespective of the initial basal state of the cortex. Thus, whereas the incremental signals of DeltaCMRglc can localize neurotransmitter activity, the magnitude of such activity during the response is represented by the total localized CMRglc, not the increment.
在清醒人类、清醒啮齿动物和灵长类动物的感觉激活过程中，大脑葡萄糖代谢率（CMRglc）的局部变化较小（10%-40%），而在麻醉大鼠和猫的感觉激活研究中，这种变化则显著更大（50%-250%）。我们的数据与文献值一致，表明在静息麻醉状态下，CMRglc的值低于静息非麻醉状态，而激活后达到的最终状态值在麻醉和非麻醉动物中相似。CMRglc在静息麻醉状态下的值较低，这就解释了为什么从麻醉状态激活时的增量比从非麻醉状态开始时更大。我们实验室最近的13C NMR测量建立了葡萄糖氧化能量学、CMRglc（氧化）与谷氨酸/γ-氨基丁酸/谷氨酰胺神经递质循环通量Vcycle之间的定量关系。在CMRglc（氧化）的静息清醒值及其刺激后的增量中，大脑能量消耗的大部分（约80%）都用于Vcycle。在功能成像的差分方法中，假定测量信号的增量变化代表支持功能反应的模块活动。然而，无论皮层的初始基础状态如何，在对刺激的反应过程中必须存在相同量的活动。因此，虽然DeltaCMRglc的增量信号可以定位神经递质活动，但反应过程中这种活动的大小由总局部CMRglc表示，而不是增量。
