Background and aims Docosahexanoic acid (DHA) is a major component of membrane phospholipids and critical for fetal neuro-development. It accumulates during late pregnancy and may protect against oxidative damage to biomembranes. Isoprostanes, neuroprostanes, and neurofurans have all become attractive biomarkers of oxidative damage and lipid peroxidation in brain tissues. Lately also F₂-dihomo-isoprostanes have emerged as an in vivo biomarker of free radical damage to myelin in white matter.

Methods Global hypoxia was induced in newborn piglets (age 12–36 h) until Base Excess -20 mmol/L or mean arterial blood pressure <20 mmHg. One group (n = 11) was resuscitated with ambient air and another (n = 10) received in addition DHA 5 mg/kg 4 h after start of resuscitation. The piglets were followed for 9½ h after end of hypoxia.

Results Treatment with 5 mg/kg DHA 4 h after severe hypoxia significantly attenuated lipid peroxidation in tissues from cortex and hippocampus. There were less Isoprostanes in cortex and hippocampus in compared with reoxygenation with air (21%) alone, p = 0.041 in cortex and p = 0.006 in hippocampus. Neuroprostanes were lower in cortex in the DHA treated group, p = 0.047. F₂-dihomo-Isoprostane, an indicator of white matter damage, was significantly lower in tissue from hippocampus in the DHA treated group, p = 0.035.

Conclusions Treatment with DHA after severe neonatal hypoxia attenuates lipid peroxidation and brain damage in both grey- and white matter tissues. These novel findings add new knowledge on oxidative injury and points at a possible therapeutic intervention after perinatal asphyxia or severe hypoxia in both term and preterm babies.