Patterns of increased glucose use following extracellular infusion of glutamate: An autoradiographic study

Hirosuke Fujisawa, Hans Landolt, Ross Bullock

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)245-254
Number of pages10
JournalJournal of neurotrauma
Volume13
Issue number5
DOIs
StatePublished - May 1996

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Keywords

  • brain ischemia
  • glucose utilization
  • glutamate
  • microdialysis
  • rats

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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