Investigation of TNF-a 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-a 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- a 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.