690 Measurement of Regional Brain Glucose Utilization In Vivo Using (2- 14 C) Glucose

ALTERED FUNCTION of body tissues is generally accompanied by changes in the rate of energy utilization commensurate with the activity (i.e., mechanical work, secretion, transport, synthesis, etc.). While nervous tissue does not participate in actual mechanical work, nerve cell activity does require the maintenance of ion gradients, synthesis of neurotransmitters and of protein; all of which are energy consuming processes. 1 ' 2 Therefore, useful information about nervous tissue function may be obtained by studying its rates of energy utilization. The level of oxidative metabolism is the most satisfactory measure of steady state aerobic energy metabolism but it is difficult to measure oxygen utilization in small animals and impossible at this time to determine it in individual brain regions or nerve cells in vivo. An alternative is to measure glucose utilization (CMRglu) which, under most circumstances, but not all, is stoichiometrically related to oxygen consumption (6 mol 0 2/mol glucose). The first experiments in which CMRglu was estimated without determining blood flow or taking arteriovenous differences, appear to have been done by Gaitonde 3 who measured the incorporation of [2- 14 C]glucose into the acid soluble metabolites of brain. Gaitonde recognized that conversion of glucose to CO2 is not immediate, rather the evolution of 14 CO2 derived from [2- u C]glucose is predictable and relatively slow. Investigators experimenting in the late 1950's and early 1960's were, in fact, disappointed to find that they could not easily measure brain CMRglu by collecting venous 14 CO2. The relative specific activity (dpm/mol carbon) of CO2 was much lower than that of glucose and took more than an hour to equilibrate. In many experiments, complete equilibration did not occur. 4 ' 6 The explanation for this phenomenon became clear when Haslam and Krebs 8