Antioxidant therapy and neuroprotection in the newborn

Injury to the perinatal brain is a leading cause of childhood mortality and lifelong disability. Despite recent improvements in neonatal care, no effective treatment for perinatal brain lesions is available. The newborn, especially if preterm, is highly prone to oxidative stress (OS) and to the toxic effect of free radicals (FRs). At birth, the newborn is exposed to a relatively hyperoxic environment caused by an increased oxygen bioavailability with greatly enhanced generation of FRs. Additional sources (e.g., inflammation, hypoxia, ischemia, glutamate and free iron release) occur, magnifying OS. In the preterm baby, the perinatal transition is accompanied by the immaturity of the antioxidant systems and the reduced ability to induce efficient homeostatic mechanisms designed to control overproduction of cell-damaging FRs. Improved understanding of the pathophysiological mechanism involved in perinatal brain lesions helps to identify potential targets for neuroprotective interventions, and the knowledge of these mechanisms has enabled scientists to develop new therapeutic strategies that have confirmed their neuroprotective effects in animal studies. Considering the growing role of OS in preterm newborn morbidity in respect to the higher risk of FR damage in these babies, erythropoietin, allopurinol, melatonin and hypothermia demonstrate great promise as potential neuroprotectans. This article provides an overview of the pathogenesis of FR-mediated diseases of the newborn and the antioxidant strategies now tested in order to reduce OS and its damaging effects.