PATTERNS OF INCREASED GLUCOSE USE FOLLOWING EXTRACELLULAR INFUSION OFGLUTAMATE - AN AUTORADIOGRAPHIC STUDY

An apparent transient increase in local glucose utilization has been d emonstrated in certain brain areas after global and focal ischemia in several models, A coincident transient increase in extracellular gluta mate has been shown in the same brain regions in many of these models, To test the hypothesis that an increase in metabolism is an important component of the excitotoxic effect of glutamate, we perfused glutama te at different concentrations (0.01, 0.1, 0.5, 1 M) into the extracel lular space, and performed 2-deoxyglucose autoradiography after 90 min of infusion, Furthermore, we infused C-14-labeled glutamate to invest igate its diffusion characteristics within the brain using autoradiogr aphic methods, Glutamate at 0.5 and 1 M concentration caused large con sistent areas of brain damage with all the histological features of ac ute infarction, although ischemia does not occur in this model, Glucos e utilization was significantly increased (115 +/- 20 vs, 56 +/- 13 mu mol/100 g/min in controls p < 0.01) in a sharply demarcated concentri c zone, at the boundary between histologically damaged and normal brai n, suggesting that viable cells not yet destroyed by glutamate respond by increased glucose metabolism, [C-14] Glutamate diffused into the b rain in a dose-dependent manner, and the pattern of its diffusion corr esponded closely to that of the histological lesion and the zone of in creased glucose uptake, We speculate that the increase in glucose use, which is not caused by ischemia in this model, is due to a metabolic response to glutamate and may be due to attempts to restore ionic home ostasis or repair cell damage.