The study of glutamate transporter 3 (EAAT3) expression, serum TNF-α level, and NF-κB activity in ischemic tolerance induced by prolonged and intermittent normobaric hyperoxia

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 amio-acid transporter 3 (EAAT3), TNF-α levels, and NF-κB 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 (normobaric 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 24h, 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 48h after pretreatment, blood sampling for assessment of serum TNF- levels were purformed. Then, the effect of InHO and PrHO on serum TNF- levels, NF-κB activity and EAAT3 expression were measured. Preconditioning with InHO and PrHO decreased NDS and upregulate EAAT3 and increase serum TNF-α level and NF-κB 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-α levels, NF-κB activity and upregulation of glutamate transporters.