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Reoxygenation with 100% Oxygen Following Hypoxia in Mice Causes Apoptosis
Yoshiro Nishimura1, Masaaki Ueki, Masaki Imanishi
1*Department of Disaster and Emergency Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan †Department of Anaesthesia, Nishiwaki Municipal Hospital, Nishiwaki, Hyogo, Japan ‡Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan §Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka, Japan ||Department of Pathology and Host Defense, Kagawa University, Kitagun, Kagawa, Japan ¶Department of Anaesthesia, Higashiosaka City Medical Center, Higashiosaka, Japan.
Abstract:
After hypoxia, reoxygenation with air is the consensus treatment for full-term neonates; however, the effect of hyperoxic reoxygenation of adults is unknown. The present study was designed to investigate the effects of reoxygenation with 100% oxygen after hypoxia on inflammation and apoptosis in mice. Eight-week-old mice were either subjected to hypoxia in 8% oxygen for 30 min or air served as controls. Following hypoxia, mice underwent reoxygenation for 30 min with 21% or 100% oxygen. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), caspase-3 and brain derived neurotrophic factor (BDNF) mRNA study and histopathological study were performed. Reoxygenation with 100% oxygen significantly increased TNF-α (2.5 h after hypoxia), IL-1β (5 h after hypoxia), caspase-3 (8 h after hypoxia) mRNA levels in the whole brain compared with 21% oxygen, and significantly decreased erythropoietin mRNA expression compared with 21% oxygen 9 h after reoxygenation. However, reoxygenation with 100% oxygen and 21% oxygen significantly decreased BDNF mRNA levels compared with control air group. There were no clear abnormal findings showing neuronal death among the three groups. Reoxygenation with 100% oxygen after hypoxia induced inflammation and apoptosis in adult mice. Therefore, these results suggest that the reoxygenation with 100% oxygen after hypoxia has harmful effects on adult brain as well as on neonatal brain.
