The cellular basis of neurovascular metabolic coupling.

Functional brain imaging studies, such as positron emission tomography and functional nuclear magnetic resonance imaging, are based on the regional increases in cerebral blood flow, glucose consumption and oxygen consumption that are associated with regional increases in neuronal activity. The cellular basis of the signals that are measured is however incompletely understood at present. An increasingly important role for astrocytes in neurovascular metabolic coupling is being described, which was already suggested over 100 years ago as astrocytes are a structural link between endothelial cells of brain capillaries and neurons. Recent data have provided evidence for a role of the astrocytic intracellular sodium concentration in driving astrocytic glycolysis that may provide neurons with lactate as an energy substrate during activation. We have previously described intracellular sodium changes in astrocytes that are associated with astrocytic intercellular calcium waves. These intercellular calcium waves have been demonstrated both in astrocytes in culture as well as in brain slices. In this paper a new hypothesis concerning a role for astrocytic intercellular calcium waves in brain energy metabolism is formulated.