Lactate and glucose as energy substrates and their role in traumatic brain injury and therapy

Abstract

Traumatic brain injury is a leading cause of disability and mortality worldwide, but no new pharmacological treatments are clinically available. A key pathophysiological development in the understanding of traumatic brain injury is the energy crisis derived from decreased cerebral blood flow, increased energy demand and mitochondrial dysfunction. Although still controversial, new findings suggest that brain cells try to cope in these conditions by metabolizing lactate as an energy substrate ‘on-demand’ in lieu of glucose. Experimental and clinical data suggest that lactate, at least when exogenously administered, is transported from astrocytes to neurons for neuronal utilization, essentially bypassing the slow, catabolizing glycolysis process to quickly and efficiently produce ATP. Treatment strategies using systemically applied lactate have proved to be protective in various experimental traumatic brain injury studies. However, lactate has the potential to elevate oxygen consumption to high levels and, therefore, could potentially impose a danger for tissue-at-risk with low cerebral blood flow. The present review outlines the experimental basis of lactate in energy metabolism under physiological and pathophysiological conditions and presents arguments for lactate as a new therapeutical tool in human head injury.