Evaluation of HIF1α expression in ischemic tolerance induced by intermittent normobaric hyperoxia in the rat model of stroke

Recent studies have shown that normobaric hyperoxia is effective in the treatment of acute ischemia, a phenomenon called preconditioning. However, the exact mechanism of this kind of preconditioning in vivo is not known. In this study, the effect of intermittent normobaric hyperoxia on expression of HIF1α in a stroke model was investigated. In this experimental study, rats were divided into 4 groups. Hyperoxia groups were exposed to 95% inspired oxygen for 4 h/day and 6 consecutive days. Oxygen concentration in the control groups was 21% (normoxia). After 24 h, rats in stroke groups were subjected to 60 min of right middle cerebral artery occlusion. After 24 h, reperfusion neurological deficit scores were assessed. The brain HIF1α levels were analyzed by Western blot. Statistical analysis was performed using two-way ANOVA, Bonferroni post-test, Fisher exact test, and GraphPad Prism 5 software. The results of this study showed that HIF1α levels increased in stroke groups compared with normoxia groups, while the amount of protein in hyperoxia groups was not significantly different from normoxia groups. Significantly increased HIF1α levels were observed in hyperoxia stroke group. Also, hyperoxia improved neurological deficit scores from 8.83% down to 3.46%. Hydroxylation, instability, and degradation of HIF1α occurred following hyperoxia. In the stroke groups, lack of oxygen delivery to cells prevents hydroxylation and degradation of HIF1α. In hyperoxia stroke group, inflammatory cytokines with increased ROS can induce increased expression of HIF1α.