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Lactate has been considered for a long time as a metabolic waste and/or a sign of hypoxia in the central nervous system. Nevertheless, clear evidence that lactate can constitute an adequate energy substrate for brain tissue has been provided as early as in the 1950s with the pioneering work of McIlwain in brain slices. Over the years, several studies using different approaches have confirmed that lactate is efficiently oxidized by brain cells in vitro. Moreover, lactate has been shown under certain circumstances to have a neuroprotective effect and support neuronal activity. Similar confirmation of lactate utilization in vivo as well as putative neuroprotection in various excitotoxic models has been provided. Lactate was even shown to restore cognitive performance upon an hypoglycemic episode in humans. More recently, it was proposed that lactate could be produced by astrocytes and released in the extracellular …