Investigation of TNF-a Converting Enzyme and Activity of NF-KB in Tolerance to Ischemia Induced by Intermittent Normobaric Hyperoxia in Rat Model

Background and objective: 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. Materials and Methods: The rats were divided into two experimental groups, each consisted of ۲۰ animals. The first group was exposed to ۹۵% inspired HO for ۴h/day for ۶ consecutive days (intermittent HO; InHO). The second group acting as the control, was exposed to ۲۱% 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 ۲۴hr, MCAO-operated subgroups were subjected to ۶۰ min of right MCAO. After ۲۴ h reperfusion, neurologic deficit score (NDS) and infarct volume were assessed in MCAO-operated subgroups. Immediately and ۴۸ 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. Results: Preconditioning with intermittent HO and ischemia decreased NDS and infarct volume. Moreover InHO and MCAO-InHO upregulate TACE and increase NF-kB activity significantly. Conclusion: 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.

Keywords:

Normobaric hyperoxia , Brain ischemia tolerance , Stroke , TACE , NF-kB activity