Iron supplementation aggravates periventricular cystic white matter lesions in newborn mice

Periventricular leukomalacia (PVL) is the main cause of neurological impairment in premature newborns. The pathogenesis of PVL remains unclear but may involve glutamate excitotoxicity and free radical production. Oxygen and iron, which are widely used in premature newborns, are oxidizing agents with a potential for promoting free radical production. We previously described a mouse model of excitotoxic neonatal white matter lesions mimicking several aspects of human PVL. In the present study, we used this mouse model to investigate whether iron pretreatment or 100% oxygen exposure worsened excitotoxic lesions. We found that iron pretreatment but not hyperoxia significantly increased white matter lesions, suggesting that high doses of iron may aggravate PVL in premature newborns.