Effect of Exogenous L-lactate on Post-ischemic Response to Injury in the Neurovascular Unit

Abstract L-lactate administration enhances functional recovery in several preclinical animal models of acute brain injury, and its protective effects have been mainly related to its metabolic functions. The neurovascular unit, consisting of endothelial cells, pericytes, glial cells and neurons, is central to brain metabolism and post-ischemic inflammation. Here, we analyzed the effect of L-lactate supplementation on the response to injury of cellular components of the neurovascular unit in the acute post-ischemic phase. When administered at reperfusion, L-lactate enhanced proliferation in the vascular compartment of the lesion. Furthermore, reactive glial cells from lactate-treated mice exhibited increased morphological complexity and differential expression of the gap-junction protein connexin 30 and the lysosomal protein CD68. Our results suggest that, in addition to its presumed ability to help overcome the hypoxic energy crisis and prevent brain cell death, L-lactate supplementation might contribute to stroke recovery by facilitating the execution and/or progression of signaling programs that promote proliferation, as well as by fine-tuning the efficiency with which glial cells confine and clear ischemic damage. Graphical Abstract L-lactate supplementation could fuel recovery after stroke and help mitigate damage extension . L-lactate could protect neurovascular unit cells from early death, promote proliferation within the lesion and refine the efficiency with which glial cells confine and clear ischemic damage, thereby preventing its spread