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J. Neurochem. (2010) 113, 735–748.

Disruption of brain energy metabolism is the hallmark of cerebral ischemia, a major cause of death worldwide. Astrocytes play a key role in the regulation of brain metabolism and their vulnerability to ischemia has been described. Aiming to quantify the effects of an ischemic insult in astrocytic metabolism, primary cultures of astrocytes were subjected to 5 h of oxygen and glucose deprivation in a bioreactor. Flux distributions, before and after ischemia, were estimated by metabolic flux analysis using isotopic information and the consumption/secretion rates of relevant extracellular metabolites as constraints. During ischemia and early recovery, 30% of cell death was observed; several metabolic alterations were also identified reflecting a metabolic response by the surviving cells. In the early recovery (∼10 h), astrocytes up‐regulated glucose utilization by 30% and …