TY - JOUR
T1 - Patterns of increased glucose use following extracellular infusion of glutamate
T2 - An autoradiographic study
AU - Fujisawa, Hirosuke
AU - Landolt, Hans
AU - Bullock, Ross
PY - 1996/5
Y1 - 1996/5
N2 - An apparent transient increase in local glucose utilization has been demonstrated in certain brain areas after global and focal ischemia in several models. A coincident transient increase in extracellular glutamate 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 glutamate at different concentrations (0.01, 0.1, 0.5, 1 M) into the extracellular space, and performed 2-deoxyglucose autoradiography after 90 min of infusion. Furthermore, we infused 14C-labeled glutamate to investigate its diffusion characteristics within the brain using autoradiographic methods. Glutamate at 0.5 and 1 M concentration caused large consistent areas of brain damage with all the histological features of acute infarction, although ischemia does not occur in this model. Glucose utilization was significantly increased (115 ± 20 vs. 56 ± 13 μmol/100 g/min in controls p < 0.01) in a sharply demarcated concentric zone, at the boundary between histologically damaged and normal brain, suggesting that viable cells not yet destroyed by glutamate respond by increased glucose metabolism. [14C] Glutamate diffused into the brain in a dose-dependent manner, and the pattern of its diffusion corresponded closely to that of the histological lesion and the zone of increased 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 homeostasis or repair cell damage.
AB - An apparent transient increase in local glucose utilization has been demonstrated in certain brain areas after global and focal ischemia in several models. A coincident transient increase in extracellular glutamate 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 glutamate at different concentrations (0.01, 0.1, 0.5, 1 M) into the extracellular space, and performed 2-deoxyglucose autoradiography after 90 min of infusion. Furthermore, we infused 14C-labeled glutamate to investigate its diffusion characteristics within the brain using autoradiographic methods. Glutamate at 0.5 and 1 M concentration caused large consistent areas of brain damage with all the histological features of acute infarction, although ischemia does not occur in this model. Glucose utilization was significantly increased (115 ± 20 vs. 56 ± 13 μmol/100 g/min in controls p < 0.01) in a sharply demarcated concentric zone, at the boundary between histologically damaged and normal brain, suggesting that viable cells not yet destroyed by glutamate respond by increased glucose metabolism. [14C] Glutamate diffused into the brain in a dose-dependent manner, and the pattern of its diffusion corresponded closely to that of the histological lesion and the zone of increased 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 homeostasis or repair cell damage.
KW - brain ischemia
KW - glucose utilization
KW - glutamate
KW - microdialysis
KW - rats
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U2 - 10.1089/neu.1996.13.245
DO - 10.1089/neu.1996.13.245
M3 - Article
C2 - 8797174
AN - SCOPUS:0029896937
VL - 13
SP - 245
EP - 254
JO - Central Nervous System Trauma
JF - Central Nervous System Trauma
SN - 0897-7151
IS - 5
ER -