Astrocytes respond to hypoxia by increasing glycolytic capacity

Astrocytes cope more readily with hypoxic insults than do neurons. We hypothesized that astrocytes can upregulate their glycolytic capacity, allowing anaerobic glycolysis to provide sufficient ATP for cell survival as well as for carrying out critical functions such as taking up glutamate. To test this hypothesis, astrocytes were subjected to hypoxia for 5 hr. Lactate dehydrogenase (LDH) and pyruvate kinase activities increased 3- to 4-fold. Examination of LDH isoenzyme patterns determined that it was the anaerobic isoenzymes that were upregulated. To determine whether increase in enzyme activity translates into increased glycolytic capacity, astrocytes were subjected to varying time periods of hypoxia, and glucose uptake was measured under conditions where astrocytes were forced to consume more ATP. This demonstrated that 8 hr of hypoxia resulted in a doubling of glycolytic capacity. We suggest that how quickly astrocytes upregulate glycolytic capacity may determine whether or not neurons within the stroke penumbra survive.