Hyperoxia and neonatal brain injury

Advances in perinatal care have led to marked improvement in survival rates of premature infants. Neurologic morbidity of these children, however, has not decreased at the same pace.

During the period of rapid brain growth, which in the human extends from the 6th month of gestation to the third year of life, silent triggers can cause active apoptotic cell death in the developing brain.

Premature infants are exposed postnatally to unphysiologically high oxygen concentrations compared to intrauterine conditions (25mm Hg partial oxygen pressure). We have demonstrated that oxygen is a powerful trigger for widespread apoptotic neuronal death in the developing rodent brain. Hyperoxia-induced cell death is associated with oxidative stress, decreased expression of survival promoting growth factors (neurotrophins), inactivation of neurotrophin-controlled pathways and an increase of pro-inflammatory cytokines.

Analysis of the brain proteome in infant rats following hyperoxia revealed changes in proteins which are involved in axon growth and guidance and in vesicle trafficking. These findings suggest that hyperoxia may result in the formation of an abnormal neuronal network and is possibly associated with decreased synaptic activity.

In additional studies, a marked protective effect could be demonstrated with the female hormone 17ß-estradiol against hyperoxia-induced brain injury. The results imply that in preterm infants, who are prematurely deprived of maternal intrauterine estrogen and are concomitantly exposed to unphysiologically high oxygen levels, estrogen supplementation may help improve neurocognitive outcome.