Exploration of the Preventive and Therapeutic Effects of D-Lactate Administration in a Mouse MCAO Model

Background: Stroke is a major global risk to human health due to its high incidence, mortality, and prevalence of associated long-term disabilities. Recent studies have highlighted a significant impact of the gut-brain axis and metabolites derived from intestinal microbiota on modulating neurological disorders, including stroke. Methods: In this study, we investigated the effects of pre- and post-treatment with D-lactate, a lactate stereoisomer mainly produced by certain gut bacteria, on stroke outcome using a transient middle cerebral artery occlusion (MCAO) mouse model. For this purpose, male C57BL/6J mice received a single administration of D-lactate or vehicle (PBS) via the tail vein either before the MCAO surgery, as a preventive approach, or upon reperfusion, as a therapeutic paradigm. Functional outcome was assessed daily using a standard neuroscore and the adhesive removal test until day three post-surgery, when mice were sacrificed. Results: Our results indicated no significant difference in infarct size, measured using cresyl violet staining, between the D-lactate and PBS groups in both pre- and post-treatment experiments. In addition, evaluation of neurological deficits and sensorimotor function showed no statistically significant differences between the interventions throughout the experiment. Conclusions: The present data suggest that treatment with D-lactate does not show a beneficial effect in our C57BL/6J mouse MCAO model.