Long‐term histological outcome after post‐hypoxic treatment with 100% or 40% oxygen in a model of perinatal hypoxic–ischemic brain injury

Abstract

Hypoxic newborns have traditionally been given supplemental oxygen, and until recently, guidelines for neonatal resuscitation recommended that 100% oxygen be used. Exposure to 100% oxygen after hypoxic injury, however, may exacerbate oxidative stress. The current study evaluated the effect of exposure to 100, 40 or 21% oxygen after neonatal hypoxic-ischemic injury on the severity of brain injury after long-term survival. The severity of histological brain injury was not different in animals exposed to 100% oxygen versus room air. Male animals treated with 40% oxygen post-hypoxia had the lowest mean total histology scores, but this was not statistically significant due to the large variation in injury within each treatment group. These results support the growing number of studies in human infants and experimental animals that show no benefit of 100% oxygen over room air for neonatal resuscitation. Our results suggest that post-hypoxia treatment with 40% oxygen may be beneficial, particularly in males. Further studies of the effects of different concentrations of oxygen on brain injury are warranted and should have sufficient power to examine sex differences.

Resuscitation with 100% oxygen increases injury and counteracts the neuroprotective effect of therapeutic hypothermia in the neonatal rat

“…We chose 30 min of reoxygenation because this is a typical resuscitation time used clinically. In contrast to our results, other investigators found no difference in brain injury in rats after reoxygenation with 100% oxygen vs. air (29), or even reduced injury after 100% oxygen in mice (30). Of note, the results in the latter study may have been distorted because more animals in the 100% O 2 group died prematurely and were excluded from the analyses.…”

Longitudinal diffusion tensor and manganese-enhanced MRI detect delayed cerebral gray and white matter injury after hypoxia–ischemia and hyperoxia

“…To our knowledge, it is the first study to examine the effect of hyperoxia after HI on long-term injury development in gray and white matter in a neonatal rat model using manganeseenhanced MRI in combination with DTI and anatomical imaging. Although some experimental studies have found no effect (10) or that hyperoxia limits injury (11), mounting experimental data indicate that hyperoxia exacerbates injury after HI in the immature brain (5,12). Our study corroborates these findings and adds important knowledge to the effect of hyperoxia on the prolonged evolution of injury in gray and white matter.…”

Post-hypoxic hypothermia is protective in human NT2-N neurons regardless of oxygen concentration during reoxygenation

“…air, 39 or even reduced injury after 100% oxygen in mice. 40 Importantly, more animals in the 100% group died prematurely and were excluded from analyses in the latter study.…”

“…A neuroprotective effect of hypothermia has been shown in both newborn animals 155, 157, 291 and clinical trials 19,39,163,164 . In line with these studies we demonstrate a protective effect of therapeutic hypothermia across all three models in the present work:…”

“…Importantly, therapeutic hypothermia may alter the predictive value of this early neurological examination (Sarnat HIE grade) on later neurodevelopmental prognosis 39,40 .…”