[Evaluation of HIF1alpha 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 HIF1alpha 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 HIF1alpha 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 HIF1alpha 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 HIF1alpha 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 HIF1alpha occurred following hyperoxia. In the stroke groups, lack of oxygen delivery to cells prevents hydroxylation and degradation of HIF1alpha. In hyperoxia stroke group, inflammatory cytokines with increased ROS can induce increased expression of HIF1alpha

[ effect of temporary middle cerebral artery occlusion on reduction of brain injuries in rat stroke model]

Recent studies suggest that sub-lethal ischemia protect the brain from subsequent ischemic injuries. This study was an effort to identify and shed light on the nature of changes in the blood brain barrier permeability and brain edema. Rats were divided into four main experimental groups, each of 21 animals. The first group acted as a model of ischemic preconditioning which was subjected to 10 minutes of temporary middle cerebral artery occlusion in the first day [tMCAO] and in the second day, was subjected to 60 min middle cerebral artery occlusion [MCAO]. The second group acted as a control group and did not receive any surgery except 60 min middle cerebral artery occlusion in the second day. The third group served as a sham group, and was subjected to surgery with 10 min of temporary middle cerebral artery occlusion [tMCAO] in the first day. The fourth group remained intact and was not subjected to any surgery. Each main group subdivided into three subgroups [n=7] for infarct volume [n=21], blood brain barrier permeability, and brain edema. After 24 hours, each main group was subjected to 60min of right MCAO occlusion. Then, neurologic deficit score [NDS], infarct volume, blood brain barrier permeability, and brain edema were assessed in the subgroups. Preconditioning with tMCAO decreased NDS and infarct volume, brain barrier permeability, and brain edema. Temporary middle cerebral artery occlusion [tMCAO] is associated with neurologic deficit scores, infarct, blood brain barrier permeability, and brain edema consistent with an active role in the genesis of ischemic protection

effect of prolonged and intermittent normobaric hyperoxia preconditioning on glutathione reductase activity in the rat stroke model

Ischemic preconditioning [IPC] is an endogenous phenomenon that can induce ischemic tolerance [IT] in a variety of organs such as brain. To investigate the intermittent and prolonged dose of normobaric hyperoxia [HO] on neurologic deficit scores, infarct volume, and glutathione reductase activity. this was an experimental study carried out in Shahid Beheshti University of Medical Sciences in Tehran, Iran. A total of 80 rats were initially divided into four main groups. The first two groups were exposed to HO in prolonged [24h; PrHO; 95% O2] and intermittent [4h - 6days; InHO; 95% O2] groups and the second two groups served as controls and exposed to 21% oxygen in the same chamber [room air, RA] continuously [24h; PrRA] and discontinuously [4h - 6days; InRA]. Each group was further subdivided into three subgroups. After 24 h, the first subgroup was subjected to 60 minutes middle cerebral artery occlusion [MCAO] followed by 24h of reperfusion. Later, the IT induced by InHO and PrHO, were measured by neurologic deficit scores and infarct volume. The second and third subgroups were marked as sham-operated and intact subgroups for assessing the effect of HO on glutathione reductase activity. Our findings indicated that the InHO and PrHO are involved in induction of IT. Pre-treatment with InHO and PrHO reduced the neurologic deficit scores and infarct volume, significantly. The InHO and PrHO caused a significant increase in glutathione reductase activity. The catalase activity of prolonged HO groups was significantly higher than that of intermittent HO groups. Although further studies are needed to clarify the mechanisms of ischemic tolerance, the InHO and PrHO seem to partly exert their effects via increased glutathione reductase activity

[ threshold assessment of ischemic tolerance induced by normobaric hyperoxia in rat stroke model]

Recent studies suggest that normobaric hyperoxia [HO] results in ischemic tolerance to reduce ischemia brain injury. In this research, attempts were made to assess threshold of ischemic tolerance induced by normobaric hyperoxia in rat stroke model. Rats were divided into two groups and each group into four experimental groups, each containing 21 animals. The first four groups were exposed to 95% inspired Ho for 4h, 8h, 16h, and 24 hr. The second four groups acted as controls, and were exposed to 21% oxygen in the same chamber [room air, RA] continuously for 4h, 8h, 16h, and 24h. All animals were subjected to 60 min right middle cerebral arterial occlusion [MCAO] 24h after pretreatment. After 24h reperfusion, each main group was subdivided to three subgroups [n=7] for assessment of neurologic deficit score [NDS], infarct volume, Evans blue [EB] extravasations, and brain water contents. Preconditioning with 16HO and 24HO decreased NDS and infarct volume significantly. Ischemic tolerance induced by 24 HO decreased EB extravasations significantly. Preconditioning with 4HO, 8HO, 16HO and 24 HO could not decrease brain water content significantly. Although further studies are necessary to clarify the mechanisms of ischemic tolerance, the lowest Ho duration for ischemic tolerance induction is 16h, but appropriate Ho duration for ischemic tolerance induction is 24 HO

Neuroprotection induced by preconditioning with prolonged and intermittent normobaric hyperoxia upregulate TNF-alpha converting enzyme and increase NF-KB activity in the rat stroke model

Ischemic preconditioning [IPC] is an endogenous phenomenon that can induce ischemic tolerance [IT] in variety of organs such as brain. In this study, we examined the intermittent and prolonged dose of normobaric hyperoxia [NBHO] in neurologic deficit scores, NF-kB activity, and TNF-alpha converting enzyme [TACE] expression. The rats were divided to four main groups. First two groups were exposed to HO divided in prolonged [24hrs; PrHO] and intermittent [4h X 6 days; InHO] groups. Second two groups acted as control groups and they were exposed to 21% oxygen with the following condition: in the same chamber [room air, RA], continuously [24hrs; Pr RA] and discontinuously [4h X 6days; InRA]. Each group was subdivided to three subgroups. After 24hrs, first subgroup was subjected to 60mins MCAO followed by 24hrs of reperfusion. Then, IT, induced by InHO and PrHO, was measured by neurologic deficit scores and infarct volume. Second and third subgroups were respectively called sham-operated subgroup and intact subgroup designed to assess the effect of HO on NF-kB activity and TNF-alpha converting enzyme expression. Our findings indicate that InHO and PrHO are involved in the induction of IT. Pretreatment with InHO and PrHO reduce neurologic deficit scores and infarct volume significantly. InHO and PrHO increase NF-kB activity and TNF-alpha converting enzyme expression with different degrees. Also, InHO with ischemia increase NF-kB activity and TNF-alpha converting enzyme expression significantly. Although further studies are needed to clarify the mechanisms of ischemic tolerance, InHO and PrHO seem partly to exert their effects via increasing NF-kB activity and up regulation of TNF-alpha converting enzyme

[Investigation of TNF-alpha converting enzyme and activity of nf-kb in tolerance to ischemia induced by intermittent normobaric hyperoxia in rat model]

Recent studies suggest that intermittent and prolonged normobaric hyperoxia [HO] results in ischemic tolerance to reduce brain injury. In this research attempts were made to see the changes in TNF-alpha converting enzyme [TACE] and NF-kB activity following intermittent HO and ischemia preconditioning. The rats were divided into two experimental groups, each consisted of 20 animals. The first group was exposed to 95% inspired HO for 4h/day for 6 consecutive days [intermittent HO; InHO]. The second group acting as the control was exposed to 21% oxygen in the same chamber [normobaric normoxia or room air; RA] continuously for six days [intermittent RA; InRA]. Each main group was subdivided to MCAO-operated [middle cerebral artery occlusion], sham-operated [without MCAO], and intact [without any surgery] subgroups. After 24hr, MCAO-operated subgroups were subjected to 60 min of right MCAO. After 24 h reperfusion, neurologic deficit score [NDS] and infarct volume were assessed in MCAO-operated subgroups. Immediately and 48 h after pretreatment, blood sampling for assessment of serum TNF-alpha levels were subjected. Then, the effect of intermittent HO and ischemia on NF-kB activity and TACE expression were measured. Preconditioning with intermittent HO and ischemia decreased NDS and infarct volume. Moreover InHO and MCAO-InHO upregulate TACE and increase NF-kB activity significantly. Although further studies are needed to clarify the mechanisms of ischemic tolerance, InHO and ischemia seem to partly exert their effects via increase upregulation of TACE and NF-kB activity