Microenvironmental changes including elevated levels Of L-glutamate, ionic homeostasis, acidification, and oxygen level are associated with brain insults. Their effects on energy metabolism were studied in cultured astrocytes. L-Glutamate caused a decrease in lactate accumulation through the activation of transporter in astrocytes in a concentration- and time-dependent manner. Decreases in glucose uptake, lactate synthesis and accumulation as well as increases in mitochondrial activity indicated a switch of the astrocytic metabolism from glycolytic to oxidative. Environmental changes co-operated with L-glutamate to regulate the metabolic strategy, e.g. KCl and oxygen deprivation reversed but acidification exacerbated the L-glutamate- mediated decrease in lactate accumulation. Taken together, during chronic exposure, oxidation of non-glucose substrates such as L-glutamate fuels the active transport of L-glutamate into astrocytes. (C) 2003 Elsevier Ireland Ltd. All rights reserved.