Maternal omega-3 fatty acid supplementation protects against lipopolysaccharide-induced white matter injury in the neonatal rat brain

Objectives: Periventricular leukomalacia (PVL) is the predominant form of brain injury in premature infants, and no specific treatment currently exists for this condition. We have evaluated whether maternal omega-3 fatty acid (omega 3 FA) treatment reduces endotoxin-induced PVL in the developing rat brain. Methods: Wistar rats with dated pregnancies were fed a standard diet or a diet enriched in omega 3 FA (70% docosahexaenoic acid + 30% eicosapentaenoic acid mixture) during gestation. Intraperitoneal injection of lipopolysaccharide (LPS) was administered consecutively on the 18th and 19th embryonic days to establish the endotoxin-induced PVL rat model. The animals were divided into four groups: (i) control, (ii) PVL, (iii) PVL+low-dose omega 3 FA and (iv) PVL+high-dose omega 3 FA. At day P7, apoptosis and hypomyelination in periventricular white matter were evaluated by immunohistochemical assessments. Results: High-dose maternal omega 3 FA treatment reduced brain weight loss. Maternal omega 3 FA treatment given either in low or high doses greatly decreased caspase-3 immunoreactivity and increased myelin basic protein immunoreactivity, indicating a decrease in apoptosis and hypomyelination. Conclusion: Considering that no specific treatment is available for PVL, maternal omega 3 FA supplementation may provide a nutritional strategy to limit periventricular white matter damage caused by infections during pregnancy.