Introduction: Brain metabolism is thought to be maintained by neuronal-glial metabolic coupling[1]. Glia take up glutamate from the synaptic cleft for conversion into glutamine, triggering glial glycolysis with production of lactate. This lactate is shuttled into neurons and further metabolized[2]. The origin and role of lactate in severe traumatic brain injury (TBI) remains controversial.

Methods: Using a modified weight drop model of severe TBI and magnetic resonance (MR) spectroscopy with infusion of 13C labeled glucose, lactate and acetate, the present study investigated the possibility that neuronal-glial metabolism is uncoupled following severe TBI.

Results: Histopathology of the model showed severe brain injury with subarachnoid and hemorrhage together with glial cell activation and positive staining for tau at 90 min post trauma. High resolution MR spectroscopy of brain metabolites revealed significant labeling of lactate at C-3 and C-2 irrespective of the infused substrates.

Conclusions: Increased 13C labeled lactate in all study groups in the absence of ischemia, implied activated astrocytic glycolysis and production of lactate with failure of neuronal uptake; i.e. a loss of glial sensing for glutamate. It is important to recognize that the early increase in extracellular lactate in severe TBI with the injured neurons unable to pick it up likely contributes to a rapid progression towards irreversible injury and pan-necrosis. Hence, a method to detect and scavenge the excess extracellular lactate on site or early following severe TBI may be a potential primary therapeutic measure.

Patient Care: The research contradicts the belief that lactate may have a therapeutic role following TBI.

Learning Objectives: 1. Understanding the origin of lactate following severe TBI. 2. Identify novel therapeutic approaches to severe TBI.

References: 1.Tsacopoulos M, Magistretti PJ. Metabolic coupling between glia and neurons. J Neurosci 1996 Feb 1;16(3):877-885. 2.Magistretti PJ. Role of glutamate in neuron-glia metabolic coupling. Am J Clin Nutr 2009 Sep;90(3):875S-880S.