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Glucose can fuel glutamate uptake in ischemic brain
R A Swanson1, J Chen, S H Graham
1Department of Neurology, Veterans Affairs Medical Center, San Francisco, California 94121.
Summary
Brain cells can clear excess glutamate during oxygen deprivation if glucose is available. This study shows glucose, not oxygen, is key for glutamate uptake in ischemic brain, preventing excitotoxicity.
Area of Science:
- Neuroscience
- Cellular Biology
- Biochemistry
Background:
- Astrocytes in cell culture maintain glutamate uptake during hypoxia when glucose is present.
- It remains unclear if this capacity extends to the brain in its natural state (in situ).
Purpose of the Study:
- To investigate if the brain in situ can maintain extracellular glutamate uptake during ischemia when glucose is supplied.
- To determine the role of glucose versus oxygen in regulating extracellular glutamate levels during cerebral ischemia.
Main Methods:
- Microdialysis probes were inserted into the caudate nuclei of rats.
- Probes were perfused with artificial cerebrospinal fluid (CSF) containing either 30 mM or 0 mM glucose.
- Global cerebral ischemia was induced via cardiac arrest, and extracellular glutamate levels were measured.
Main Results:
- In the absence of glucose, extracellular glutamate increased 50-fold during ischemia.
- Supplying glucose to the perfusate reduced this glutamate rise to less than 20% of glucose-free levels.
- The glucose-mediated reduction in glutamate was blocked by threo-beta-hydroxyaspartate, a glutamate uptake inhibitor.
Conclusions:
- Efficient uptake of extracellular glutamate in the brain does not require oxygen.
- Elevated extracellular glutamate during ischemia is primarily due to metabolic issues other than hypoxia.
- Maintaining glucose supply is crucial for preventing excitotoxicity during ischemic events.