Measurement of Cerebral Glucose Utilization Using Washout After Carotid Injection in the Rat

The carotid injection technique, used previously to quantitate the kinetics of blood‐brain barrier transport of metabolic substrates, may be modified to analyze the rate of cerebral glucose utilization. A 0.2‐ml solution of [ 14 C]glucose (G F ) and [ 3 H]methylglucose (M), an internal reference, is rapidly injected into the carotid artery, followed by microwave fixation of brain at various times up to 4 min after injection. The brain radioactivity is separated into a fraction containing neutral hexoses (G F and M) and a fraction containing metabolites of glucose. The G F /M ratio is related to the rate constant ( k 3 ) of brain glucose utilization by the simple, linear equation: In(G F /M) = In(G F °/M°) – k 3 t , where G F °/M°= the brain uptake index of glucose, relative to methylglucose, at 5‐15 s after injection, and t = the time after carotid injection, e.g., 1–4 min. It is assumed that (a) the rate of influx due to recirculation of label is minimal during the 4‐min circulation period; and (b) the rate constants of glucose efflux ( k 2 ) and methylglucose efflux ( k 2 *) are identical. Independent estimates of k 2 and k 2 * showed these parameters to be identical: k 2 = 0.14 + 0.08 min‐I; k 2 * = 0.14 ± 0.02 min‐I. A logarithmic plot of G F /M ratios versus time was linear (r = 0.99), and was described by the slope k 2 = 0.21 ± 0.02 min −1 . Assuming glucose is uniformly distributed in brain, then the glycolytic rate = k 3 × brain glucose = (0.21 min −1 ) (2.6 μmol g −1 ) = 0.55 μmol min −1 g −1 for the cortex of the barbiturate‐anesthetized rat. These studies provide the basis for a simple method of measurement of regional brain glycolysis that does not require either the use of correction factors, e.g., the lumped constant, or the use of differentially labeled glucose.