Short‐ and long‐term behavioral effects of exposure to 21%, 40% and 100% oxygen after perinatal hypoxia–ischemia in the rat

Abstract

Until recently, supplementation with 100% oxygen was standard therapy for newborns who required resuscitation at birth or suffered later hypoxic-ischemic events. Exposure to high concentrations of oxygen, however, may worsen oxidative stress induced by ischemic injury. In this study we investigated the short- and long-term behavioral outcomes in rats that had undergone hypoxic-ischemic brain injury on postnatal day 7, followed by 2h exposure to 21%, 40%, or 100% oxygen, compared to normal controls. There were no differences in the development of walking, head lifting and righting reflexes from postnatal days 9 to 15. Cliff avoidance showed some abnormal responses in the H21 animals. From postnatal days 28 to 56, three tests of sensorimotor coordination were performed weekly: ledged tapered beam, cylinder, and bilateral tactile stimulation. The ledged tapered beam test without prior training of animals was sensitive to injury, but did not distinguish between treatment groups. The cylinder test showed a greater use of the unimpaired limb in female 21% and 40% oxygen groups compared to controls. Performance in both cylinder and the beam tests showed a correlation with the degree of brain injury. The bilateral tactile stimulation test showed that the male 21% oxygen groups had worse sensory asymmetry than male 40% or 100% oxygen groups, but was not statistically significantly different from controls. We thus found a minor benefit to post-hypoxia-ischemic treatment with 100% and 40% oxygen compared to 21% in one test of early motor skills. Our results for long-term sensorimotor behavior, however, showed conflicting results, however, as males treated with 40% or 100% oxygen had less sensory asymmetry (better performance) in the bilateral tactile stimulation test than males treated with 21% oxygen, while females had impaired motor performance in the cylinder test with both 21% and 40% oxygen.

The effect of resuscitation in 100% oxygen on brain injury in a newborn rat model of severe hypoxic-ischaemic encephalopathy

“…Most animal resuscitation studies use a duration of 120 minutes for the duration of the reoxygenation period. 7,8,10,12 We used 30 minutes of resuscitation because this more closely replicates newborn resuscitation in the delivery suite, and allowed comparison with our previous study of hyperoxia in the moderate model. The resuscitation period followed immediately after the end of the insult to allow fast reoxygenation, as may be expected during an emergency resuscitation in the delivery room.…”

“…11 A study by Woodworth et al looked at short-and long-term behavioural effects following resuscitation in air, 40%, or 100% oxygen in postnatal day 7 (P7) rats. 12 They found conflicting long-term results for males (improved sensory skills in both oxygen treated groups) and females (worsened motor skills in air and 40% oxygen group). We have also previously studied the effect of resuscitation in 100% oxygen in combination with therapeutic hypothermia in a P7 rat model of moderate HI, and found that resuscitation in 100% oxygen counteracted the effect of therapeutic hypothermia with an increase in brain damage and worsening of reflex performance.…”