EXPRESS: NEUROPROTECTIVE EFFICACY OF AN OMEGA-3 DIGLYCERIDE EMULSION IN A PIGLET MODEL OF NEWBORN HYPOXIC-ISCHEMIC BRAIN DAMAGE.

BACKGROUND: Acute injection of omega-3 fatty acids (n-3) formulated in a novel diglyceride (DG) lipid emulsion is neuroprotective after hypoxic-ischemic encephalopathy (HIE) in neonatal rodents. METHODS: the efficacy of acute n-3 DG emulsion treatment was tested in 2-3-day-old piglets subjected to bilateral carotid artery clamping and 8% O₂ exposure for 30 min. Animals were randomly assigned to normothermia or hypothermia (HT, 34 ± 0.5 °C), then to n-3 DG or vehicle administration 30 min post-HI. Brain activity was assessed by amplitude-integrated EEG over 6 h. Brain injury was analyzed by TUNEL, GFAP and IBA-1 staining, ¹H-NMR spectroscopy (Lactate/NAA, Glutamate/NAA), and Western blot (caspase-3, TNF-α, IL-1β, protein carbonylation). RESULTS: n-3 DG was well tolerated, with no hemodynamic or respiratory side effects. HT alone moderately improved brain activity and only reduced inflammation, whereas n-3 DG treatment partially restored early EEG recovery, attenuated cell death and neuroinflammatory markers, and limited protein carbonyl formation and GFAP+ cell loss. Notably, n-3 DG efficacy was preserved under HT conditions. CONCLUSIONS: These results support the neuroprotective potential of n-3 DG emulsion in a piglet model of HIE, with promising implications for clinical translation.