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Comparative Study
. 2008 Feb;76(2):261-70.
doi: 10.1016/j.resuscitation.2007.07.022. Epub 2007 Aug 31.

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

Alberto Mendoza-Paredes  1 , Huiping Liu, Gregory Schears, Zajfang Yu, Scott D Markowitz, Steven Schultz, Peter Pastuszko, William J Greeley, Vinay Nadkarni, Joanna Kubin, David F Wilson, Anna Pastuszko
Affiliations
Comparative Study

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

Alberto Mendoza-Paredes et al. Resuscitation. 2008 Feb.

Abstract

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 6h 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.

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Figures

Figure 1
Figure 1. A and B. Level of Bcl-2 in four regions of piglet brain measured after 6-hr recovery following repetitive apnea with resuscitation with 21% and 100% of oxygen
The results are means from 7 experiments ± SD. The data are expressed in % of the control (sham operated). ap<0.01 for significant difference from control; bp<0.05 and cp<0.01 for significant difference between 21% oxygen and 100% of oxygen groups of animals, as determined by one-way analysis of variance, followed by Mann–Whitney test.
Figure 1
Figure 1. A and B. Level of Bcl-2 in four regions of piglet brain measured after 6-hr recovery following repetitive apnea with resuscitation with 21% and 100% of oxygen
The results are means from 7 experiments ± SD. The data are expressed in % of the control (sham operated). ap<0.01 for significant difference from control; bp<0.05 and cp<0.01 for significant difference between 21% oxygen and 100% of oxygen groups of animals, as determined by one-way analysis of variance, followed by Mann–Whitney test.
Figure 2
Figure 2. A and B. Level of Bax in four regions of piglet brain measured after 6-hr recovery following repetitive apnea with resuscitation of 21% and 100% of oxygen
The results are means from 7 experiments ± SD. The data are expressed in % of the control (sham operated). ap<0.05 for significant difference from control; bp<0.05 for significant difference between 21% oxygen and 100% of oxygen groups of animals, as determined by one-way analysis of variance, followed by Mann–Whitney test.
Figure 2
Figure 2. A and B. Level of Bax in four regions of piglet brain measured after 6-hr recovery following repetitive apnea with resuscitation of 21% and 100% of oxygen
The results are means from 7 experiments ± SD. The data are expressed in % of the control (sham operated). ap<0.05 for significant difference from control; bp<0.05 for significant difference between 21% oxygen and 100% of oxygen groups of animals, as determined by one-way analysis of variance, followed by Mann–Whitney test.
Figure 3
Figure 3. A and B. Effect of repetitive apnea with resuscitation of 21% and 100% of oxygen on level of Caspase-3 in four regions of piglet brain tissue measured after 6-hr recovery
The results are means from 7 experiments ± SD. The data are expressed in % of the control (sham operated). ap<0.05 and bp<0.01 for significant difference from control; cp<0.05 for significant difference between 21% oxygen and 100% of oxygen groups of animals, as determined by one-way analysis of variance, followed by Mann–Whitney test.
Figure 3
Figure 3. A and B. Effect of repetitive apnea with resuscitation of 21% and 100% of oxygen on level of Caspase-3 in four regions of piglet brain tissue measured after 6-hr recovery
The results are means from 7 experiments ± SD. The data are expressed in % of the control (sham operated). ap<0.05 and bp<0.01 for significant difference from control; cp<0.05 for significant difference between 21% oxygen and 100% of oxygen groups of animals, as determined by one-way analysis of variance, followed by Mann–Whitney test.
Figure 4
Figure 4. A and B. Effect of repetitive apnea with resuscitation of 21% and 100% of oxygen on level of phosphorylated Akt in four regions of piglet brain tissue measured after 6-hr recovery
The results are means from 7 experiments ± SD. The data are expressed in % of the control (sham operated). ap<0.01 for significant difference from control; bp<0.01 for significant difference between 21% oxygen and 100% of oxygen groups of animals, as determined by one-way analysis of variance, followed by Mann–Whitney test.
Figure 4
Figure 4. A and B. Effect of repetitive apnea with resuscitation of 21% and 100% of oxygen on level of phosphorylated Akt in four regions of piglet brain tissue measured after 6-hr recovery
The results are means from 7 experiments ± SD. The data are expressed in % of the control (sham operated). ap<0.01 for significant difference from control; bp<0.01 for significant difference between 21% oxygen and 100% of oxygen groups of animals, as determined by one-way analysis of variance, followed by Mann–Whitney test.
Figure 5
Figure 5. A and B. Effect of repetitive apnea with resuscitation of 21% and 100% of oxygen on level of phosphorylated CREB in four regions of piglet brain tissue measured after 6-hr recovery
The results are means from 7 experiments ± SD. The data are expressed in % of the control (sham operated). ap<0.01 for significant difference from control; bp<0.01 for significant difference between 21% oxygen and 100% of oxygen groups of animals, as determined by one-way analysis of variance, followed by Mann–Whitney test.
Figure 5
Figure 5. A and B. Effect of repetitive apnea with resuscitation of 21% and 100% of oxygen on level of phosphorylated CREB in four regions of piglet brain tissue measured after 6-hr recovery
The results are means from 7 experiments ± SD. The data are expressed in % of the control (sham operated). ap<0.01 for significant difference from control; bp<0.01 for significant difference between 21% oxygen and 100% of oxygen groups of animals, as determined by one-way analysis of variance, followed by Mann–Whitney test.
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