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

ABSTRACT

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