Abstract
Free radicals play a role of paramount importance in the development of neonatal brain injury. Depending on the pathophysiological mechanisms underlying free radical overproduction and upon specific neonatal characteristics, such as the GA-dependent maturation of antioxidant defenses and of cerebrovascular autoregulation, different profiles of injury have been identified. The growing evidence on the detrimental effects of free radicals on the brain tissue has led to discover not only potential biomarkers for oxidative damage, but also possible neuroprotective therapeutic approaches targeting oxidative stress. While a more extensive validation of free radical biomarkers is required before considering their use in routine neonatal practice, two important treatments endowed with antioxidant properties, such as therapeutic hypothermia and magnesium sulfate, have become part of the standard of care to reduce the risk of neonatal brain injury, and other promising therapeutic strategies are being tested in clinical trials. The implementation of currently available evidence is crucial to optimize neonatal neuroprotection and to develop individualized diagnostic and therapeutic approaches addressing oxidative brain injury, with the final aim of improving the neurological outcome of this population.
Highlights
Oxygen (O2 ) plays a key role in mitochondrial oxidative phosphorylation and in the activity of several oxidative enzymes
The developing brain is susceptible to oxidative stress; as such, free radicals are deeply involved in the pathophysiology of neonatal brain injury, with relevant clinical and therapeutical implications. This narrative review aims to point out the role of free radicals in the development of neonatal brain injury in both term and preterm neonates by providing a detailed overview on the underlying pathophysiological mechanisms, currently available oxidative biomarkers and the novel antioxidant therapeutic options which have been explored in clinical settings so far
Are rich in iron, which supports their differentiation [57]; as a result, these cells are vulnerable to the iron-related mechanisms of oxidative damage. This event cascade is further supported by the evidence, in neonatal rat models of intraventricular hemorrhage (IVH), of increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels in the periventricular white matter adjacent to the ventricles involved by the hemorrhage [58,59] and of impaired mitochondrial function in premyelinating oligodendrocytes (pre-OL) exposed to hemoglobin-induced oxidative stress [60]
Summary
Oxygen (O2 ) plays a key role in mitochondrial oxidative phosphorylation and in the activity of several oxidative enzymes. At low/moderate concentrations, free radicals are involved in several physiological processes, including mitogenic responses, modulation of the immune system, vascular regulation. For this reason, ROS and RNS levels are tightly regulated by specific antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GP) [1]. The balance between ROS/RNS levels and antioxidant enzyme capacities defines the redox homeostasis and protects biological structures from oxidative damage; when this balance is shifted towards a free radical overproduction, oxidative stress develops [1]. This narrative review aims to point out the role of free radicals in the development of neonatal brain injury in both term and preterm neonates by providing a detailed overview on the underlying pathophysiological mechanisms, currently available oxidative biomarkers and the novel antioxidant therapeutic options which have been explored in clinical settings so far
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