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


CONCLUSIONS
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.
Mendoza-Paredes
Alberto
A
Department of Biochemistry & Biophysics, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Liu
Huiping
H
Schears
Gregory
G
Yu
Zajfang
Z
Markowitz
Scott D
SD
Schultz
Steven
S
Pastuszko
Peter
P
Greeley
William J
WJ
Nadkarni
Vinay
V
Kubin
Joanna
J
Wilson
David F
DF
Pastuszko
Anna
A
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D053148:Caspase 3 / Q000096:biosynthesis; D050792:Circulatory Arrest, Deep Hypothermia Induced; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D010100:Oxygen / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D013552:Swine; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D051025:bcl-Associated Death Protein / Q000096:biosynthesis
D015415:Biomarkers; D017362:Cyclic AMP Response Element-Binding Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D010100:Oxygen