Impact of room air resuscitation on early growth response gene-1 in a neonatal piglet model of cerebral hypoxic ischemia.
Early growth response gene-1 (Egr-1) is up-regulated by hypoxia-ischemia (HI) and reactive oxygen species (ROS) in adult animals, functioning as a master switch in inflammation and thrombogenesis. We hypothesized that resuscitation from HI with 100% O2 would result in greater Egr-1 expression, ROS, and cell death (CD) in the brains of newborn piglets than 21% O2. Two control groups breathed 21% O2 for 1 h followed by 21% or 100% O2 for 1 h. Two HI groups underwent carotid artery occlusion and breathed 8-12% O2 for 1 h followed by occlusion release and 21% or 100% O2 for 1 h. Brain Egr-1 mRNA and protein were analyzed via quantitative PCR and Western blot. CD and ROS were measured by fluorescence microscopy. Egr-1 mRNA expression increased throughout the brain in response to HI with regional heterogeneity, but protein levels did not. Resuscitation with 100% oxygen did not cause any additional Egr-1 mRNA, Egr-1 protein, CD, or ROS production as compared with 21% oxygen. There was no difference in physiologic recovery after HI with room air compared with 100% O2 resuscitation. However, 100% O2 administration was associated with increased CD in the brainstem independent of HI. Therefore, 100% O2 may have been toxic to some brainstem cells and potentially have significance in long-term neurologic sequelae seen after neonatal HI/resuscitation. Egr-1 protein levels may be tightly regulated in an attempt to diminish neurotoxicity or to enhance plasticity at this stage of development.
Department of Pediatrics, Uniformed Services University of the Helath Sciences, Bethesda, MD 20814, USA.
Melissa M
MM
Tyree
Clifton
C
Dalgard
J Timothy
JT
O'Neill
D000388:Air; D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012151:Resuscitation; D013552:Swine
D051766:Early Growth Response Protein 1; D017382:Reactive Oxygen Species; D010100:Oxygen