study of glutamate transporter 3 [EAAT3] expression, serum TNF-alpha level, and NF-KB activity in ischemic tolerance induced by prolonged and intermittent normobaric hyperoxia

ABSTRACT

Recent studies suggest that intermittent and prolonged normobaric hyperoxia [HO] results in ischemic tolerance to preventing ischemia brain injury. In this research attempts were made to see the changes in excitatory amino-acid transporter 3 [EAAT3], TNF- alpha levels, and NF- kappa B activity following prolonged and intermittent NBHO preconditioning. Rats were divided into four experimental groups, each with 21 animals. The first two groups were exposed to 95% inspired HO for 4h/day for 6 consecutive days [intermittent HO; InHO] or for 24 continuous hours [prolonged HO; PrHO]. The second two groups acted as controls, and were exposed to 21% oxygen in the same chamber [nomobaric normoxia, RA; room air] continuously for six days [intermittent RA, InRA] or for 24 hours [prolonged RA; PrRA]. Each main group was subdivided to MCAO- operated [middle cerebral artery occlusion], sham-operated [without MCAO], and intact [without any surgery] subgroups. After 24 h, MCAO-operated subgroups were subjected to 60min of right MCAO. After 24h reperfusion, neurologic deficit score [NDS] were assessed in MCAO-operated subgroups. Immediately and 48 h after pretreatment, blood sampling for assessment of serum TNF- alpha levels were performed. Then, the effect of InHO and PrHO on serum TNF - alpha levels, NF - kappa B activity and EAAT3 expression were measured. Reconditioning with InHO and PrHO decreased NDS and upregulate EAAT3 and increase serum TNF- alpha level and NF- kappa B activity significantly. Although further studies are needed to clarify the mechanisms of ischemic tolerance, InHO and PrHo seems to partly exert their effects via increase in serum TNF- alpha levels, NF- kappa B activity and upregulation of glutamate transporters