Oxidative stress (OS) is defined as an unbalance between prooxidant and antioxidant factors that can lead to cellular and tissue damage.The newborn, especially if preterm, is highly prone to OS and to the toxic effect of free radicals (FR). At birth, the newborn is exposed to a relatively hyperoxic environment caused by an increased oxygen bioavailability with greatly enhanced generation of FR. Additional sources (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 FR. 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, a strict control of oxygen administration, lutein, melatonin, and hypothermia show great promise as potential neuroprotectants. This review provides an overview of the pathogenesis of free radical-mediated diseases of the newborn and the antioxidant strategies for now tested to reduce the OS and its damaging effects.

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Melatonin reduces OS and inflammatory cells recruitment and glial cells activation in cerebral cortex after neonatal HI damage. These results lay the groundwork for future clinical studies in infants.

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• Arterial spin labelling MRI can predict outcome in neonates with hypoxic-ischemic encephalopathy • Basal ganglia and thalami perfusion is higher in neonates with adverse outcome • Arterial spin labelling complements known MRI parameters in the prediction of outcome • The combined information of ASL and MRS measurements is the best predictor of outcome.