Free Radicals and Brain Damage in the Newborn

Abstract

Newborns and particularly preterm infants are at high risk of oxidative stress and they are very susceptible to free radical oxidative damage. Indeed, there is evidence of an imbalance between antioxidant- and oxidant-generating systems which causes oxidative damage. The brain may be especially at risk of free radical-mediated injury because neuronal membranes are rich in polyunsaturated fatty acids and because the human newborn has a relative deficiency of brain superoxide dismutase and glutathione peroxidase. The brain of the term fetus is at higher risk of oxidative stress than that of the preterm fetus, as a consequence of its higher concentration of polyunsaturated fatty acids and the maturity of the N-methyl-D-aspartate receptor system at term. There seems to be a maturation-dependent window of vulnerability to free radical attack during oligodendrocyte development. Early in its differentiation, the oligodendrocyte may be vulnerable because of active acquisition of iron for differentiation at a time of relative delay in the development of certain key antioxidant defenses in the brain. Excess free iron and deficient iron-binding and -metabolizing capacity are additional features favoring oxidant stress in premature infants. Free radicals may be generated by different mechanisms, such as ischemia-reperfusion, neutrophil and macrophage activation, Fenton chemistry, endothelial cell xanthine oxidase, free fatty acid and prostaglandin metabolism and hypoxia. Reactive oxidant production by these different mechanisms contributes in a piecewise manner to the pathogenesis of perinatal brain injury.

Optimal Oxygenation of Extremely Low Birth Weight Infants: A Meta-Analysis and Systematic Review of the Oxygen Saturation Target Studies

“…The understanding that oxidative stress is not only caused by oxygen represented a fundamental leap forward [6]. A number of free radical generating systems were identified after we first understood the important role of the oxygen radical generating system hypoxanthine-xanthine oxidase as an explanation of reoxygenation injury [7,8,9,10]. …”

Postnatal Hyperoxia Exposure Differentially Affects Hepatocytes and Liver Haemopoietic Cells in Newborn Rats

“…However, many authors recommend limitation of hyperoxia exposure in the newborn period due to increased awareness about its noxious effects [1]–[3]. Premature newborns, in particular, are known to be more susceptible to oxidative stress due to immaturity of the antioxidant system [4]–[5] and due to deficiency of antioxidant precursors in parenteral nutrition [6]. The role of hyperoxia in the pathogenesis of bronchopulmonary dysplasia and retinopathy of prematurity has been widely studied but the effects of neonatal hyperoxia on the other organs have not yet been fully considered.…”

Signaling Pathways Triggered by Oxidative Stress That Mediate Features of Severe Retinopathy of Prematurity

“…1 Early thinking focused on tissue damage from excessive generated reactive oxygen species (ROS). 2 potentially due to various oxygen stresses 3;4;5;6 , changes in photoreceptor metabolism during darkness 7;8 , and the high concentration of polyunsaturated fatty acids in photoreceptors 9 . In fact, studies were performed decades ago to test vitamin E as an antioxidant to reduce ROP, but these investigations were stopped because of complications of sepsis and necrotizing enterocolitis.…”