Hyperoxia and the Immature Brain

Abstract

Despite major advances in obstetrics and neonatal intensive care, preterm infants frequently suffer from neurological impairments in later life. Preterm and also full-term neonates are generally susceptible to injury caused by reactive oxygen species due to the immaturity of endogenous radical scavenging systems. It is well known that high oxygen levels experienced during the critical phase of maturation can profoundly influence developmental processes. Supraphysiological oxygen concentrations used for resuscitation or in the care of critically ill infants are known to have deleterious effects on the developing lung and retina, contributing to the pathophysiology of neonatal diseases like bronchopulmonary dysplasia and retinopathy of prematurity. Moreover, experimental work from the last decade suggests that hyperoxia also leads to neuronal and glial cell death, contributing to the injury of white and grey matter observed in preterm infants. During the critical phase of brain maturation, hyperoxia can alter developmental processes, resulting in the disruption of neural plasticity and myelination. However, oxygen therapy can often not be avoided in neonatal intensive care. Therefore, in situations requiring oxygen supplementation, in addition to the development of appropriate monitoring systems, protective and/or regenerative strategies are highly warranted. Here, we summarise the clinical and experimental evidence as well as potential therapeutic strategies, providing an overview of the pathophysiology of oxygen exposure on the developing central nervous system and its impact on neonatal brain injury.

Protection of Oligodendrocytes Through Neuronal Overexpression of the Small GTPase Ras in Hyperoxia-Induced Neonatal Brain Injury

“…Furthermore, long-term analyses of neurodevelopmental behavior and of axonal function/integrity would have strengthened our hypothesis. However, previous experimental studies combined with clinical data provide clear evidence for a good correlation between alterations of WM development and long-term behavioral deficits as well as axonal integrity and function ( 14 , 18 – 21 , 39 ).…”

“…Oxygen-induced preterm birth-related brain injury is associated with subtle neurodegeneration and impaired WM development resulting in long-lasting decrease of fractional anisotropy and diffusivity in the WM associated with neurodevelopmental disturbances ( 17 , 19 – 21 , 38 , 39 ). Myelination is the key for efficient nerve conduction velocity proposed to strengthen circuitry throughout the nervous system ( 40 ).…”

Cell Death in the Developing Brain after Hypoxia-Ischemia

“…In the developing brain, cell damage can be induced by a variety of insults, such as hypoxia (Schwartz et al, 2004 ), hyperoxia (Reich et al, 2016 ), hypoxia-ischemia (Rice et al, 1981 ), trauma (Bittigau et al, 2004 ), and inflammation/infections (Strunk et al, 2014 ). However, most knowledge on mechanisms of cell death emanates from studies in vivo and in vitro in models of hypoxia-ischemia so therefore we will focus mostly on that work.…”

Effects of neonatal hyperoxia on the critical period of postnatal development of neurochemical expressions in brain stem respiratory-related nuclei in the rat

“…Unfortunately, such treatment can be detrimental and often leads to retinal, pulmonary, and brain pathologies (Reich et al. ). In the respiratory system of rodents, neonatal hyperoxia impairs carotid body oxygen sensing function, blunts hypoxic phrenic response, reduces alveolar number and radial alveolar counts, and inhibits alveolar growth and pulmonary remodeling (Shaffer et al.…”