Lactate and Hypothermia: A Dual Approach for Neuroprotection in Neonatal Hypoxia-Ischemia

Motivation: Lactate, a key energy source for neurons, plays a critical role in brain function. Given its importance for neuronal activity, we ask: could it also offer neuroprotection in neonatal hypoxia-ischemia (NHI), a condition characterized by cerebral energy deficits? Goal(s): Nearly half of affected newborns show limited response to current therapeutic hypothermia (TH). This study examines whether combining lactate administration with TH improves neuroprotective outcomes. Approach: Using the Rice-Vannucci model, we optimized TH parameters and conducted MRI, behavioral tests, and protein analysis. Results: Lactate combined with TH showed greater neuroprotective effects, reducing brain lesion volumes and enhancing recovery compared to TH alone. Impact: Lactate administration showed neuroprotection in NHI. Our retrospective clinical evaluation tracking blood parameters during sodium L-lactate infusion in preterm infants confirmed the safety of lactate administration, even with elevated lactatemia at birth, indicating promising potential for clinical pediatric applications.