Resuscitation with 100%, compared with 21%, oxygen following brief, repeated periods of apnea can protect vulnerable neonatal brain regions from apoptotic injury

Purpose: To determine the effect of repeated intermittent apnea and resuscitation with 100% vs. 21% oxygen enriched gas on levels of key regulatory proteins contributing to cell death (Bax, Caspase-3) or protecting neurons from hypoxic/ischemic injury (Bcl-2, p-Akt, p-CREB). Methods: The anaesthetized, mechanically ventilated newborn piglets underwent 10 episodes of apnea with resuscitation either with 100% or with 21% oxygen. Following 6 h recovery the animals were sacrificed painlessly, the brain dissected out and used to determine levels of Bcl-2, Bax, Caspase-3, p-Akt and p-CREB in the striatum, frontal cortex, midbrain and hippocampus were studied. Results: In hippocampus and striatum, Bcl-2 expression was higher with 100% vs. 21% group (173 ± 29% vs. 121 ± 31%, p < 0.05 and 189 ± 10% vs. 117 ± 47%, p < 0.01, respectively) whereas the Bax expression was lower (88 ± 3% vs. 100 ± 9%, p < 0.05 and 117 ± 5% vs. 133 ± 10%, p < 0.05, respectively). Expression of Caspase-3 in the striatum, was lower with 100% vs. 21% group (197 ± 35% vs. 263 ± 33%, p < 0.05, respectively) but not different in the hippocampus. p-Akt expression was higher with 100% vs. 21% oxygen in the hippocampus and striatum (225 ± 44% vs. 108 ± 35%, p < 0.01 and 215 ± 12% vs. 164 ± 16%, p < 0.01, respectively). The p-CREB expression was higher with 100% vs. 21% oxygen resuscitation in the hippocampus (217 ± 41% vs. 132 ± 30%, p < 0.01) with no changes in striatum. Much smaller or insignificant differences between 100% vs. 21% oxygen groups were observed in the frontal cortex and midbrain, respectively. Conclusion: In neonatal piglet model of intermittent apnea, selectively vulnerable regions of brain (striatum and hippocampus) are better protected from apoptotic injury when resuscitation was conducted with 100%, rather than 21%, oxygen.