Effects of Lactate on Improving Cognitive Function and Survival Rate in a Mouse Model of Post-Sepsis Cognitive Impairment

BACKGROUND: Post-sepsis cognitive impairment (PSCI) represents a prevalent complication observed in survivors of sepsis, manifesting as neurocognitive deficits, including memory impairment and attentional deficits. The precise mechanisms contributing to PSCI are inadequately understood, and there is a notable absence of effective clinical interventions. Lactate, previously considered as a metabolic byproduct, has recently been recognized as a potential energy source and signaling molecule involved in various physiological and pathological processes that are intricately linked to clinical outcomes of sepsis. This study aimed to explore the neuroprotective effects of lactate on PSCI and to elucidate the underlying mechanisms. METHODS: Sixty male C57BL/6 mice were randomly assigned to three groups: control, sepsis-induced cognitive impairment, and lactate treatment groups. Sepsisassociated cognitive impairment was induced by cecal ligation and puncture. Lactate was administered via daily intraperitoneal injection (1 mol/L, 10 µL/g) for 10 consecutive days beginning 24 hours after surgery, while control groups received saline. Survival and body weight were monitored for 20 days. Cognitive performance was evaluated between days 10 and 15 using established behavioral paradigms. Brain tissue was subsequently collected for histological and molecular analyses. RESULTS: levels, and modulated inflammatory cytokine production. Mechanistically, lactate upregulated the expression of glucose transporter 1 (GLUT1) in brain tissue. This facilitated glucose utilization and diminished pyruvate accumulation, potentially influencing energy metabolism. Concurrently, lactate also reduced Malondialdehyde (MDA) levels and elevated Superoxide Dismutase (SOD) activity to mitigate oxidative damage. CONCLUSIONS: Lactate emerges as a promising neuroprotective agent against PSCI potentially influencing cerebral energy metabolism, alleviating oxidative stress, and inhibiting neuroinflammation and neuronal damage.