Astrocytes respond to hypoxia by increasing glycolytic capacity

Astrocytes cope more readily with hypoxic insults than do neurons, We hypot hesized 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 t his hypothesis, astrocytes were subjected to hypoxia for 5 hr. Lactate dehy drogenase (LDH) and pyruvate kinase activities increased 3- to 4-fold. Exam ination of LDH isoenzyme patterns determined that it was the anaerobic isoe nzymes that were upregulated, To determine whether increase in enzyme activ ity translates into increased glycolytic capacity, astrocytes were subjecte d to varying time periods of hypoxia, and glucose uptake was measured under conditions where astrocytes were forced to consume more ATP This demonstra ted that 8 hr of hypoxia resulted in a doubling of glycolytic capacity, We suggest that how quickly astrocytes upregulate glycolytic capacity may dete rmine whether or not neurons within the stroke penumbra survive. J, Neurosc i Res. 57:255-260, 1999, (C) 1999 Wiley-Liss, Inc.