Perisynaptic astrocytes normally provide fast take-up of glutamate released during synaptic activity. In pathological conditions however, extracellular glutamate levels can be abnormally high and neurotoxic (Wang and Qin, 2010). Part of this glutamate can be cleared via glutamate transporters located in the capillary endothelial cells that form the blood-brain-barrier. The efficacy of such efflux depends on the glutamate concentration gradient between blood and interstitial fluid (Teichberg et al., 2009). Meanwhile, blood glutamate content can be lowered by activation of a blood-resident enzyme glutamate–pyruvate transaminase that in the presence of pyruvate transforms glutamate into 2-ketoglutarate (Gottlieb et al., 2003), thus reducing the glutamate blood concentration. This should favor the glutamate flux from the interstitial fluid to the blood. Therefore, extracellular glutamate levels can be controlled in part by blood pyruvate, which can enhance the brain-to-blood glutamate efflux.

Indeed, Zlotnik and co-authors demonstrated (Zlotnik et al., 2008, 2012) that intravenous injection of pyruvate after traumatic brain injury in rats led to a transient decrease in blood glutamate levels and significantly improved neurological outcome during the first days following injury as well as hippocampal neuron survival at 30 days after injury.   Full article -> click here