Study on the effect of neuroprotective prolonged and intermittent normobaric hyperoxia on serum level of TNF-α and glutamate transporters expression in rat brain

Introduction: Prolonged and intermittent oxygen pre-exposure is associated with protection against ischemic reperfusion (IR) injury. In the current study, attempts were made to investigate the relationship between exposure to prolonged and intermittent normobaric hyperoxia (NBHO) and expression of excitatory amino acids transporters (EAATs) and TNF-α level. Method: Rats were divided into four main experimental groups, each of 21 animals. The first two were exposed to 95% inspired NBHO 4 h/day for 6 consecutive days (intermittent NBHO) or for 24 continuous hours (prolonged NBHO). The second two groups considered as controls and were exposed to 21% oxygen in the same chamber (normobaric normoxia, NBNO). Each main group was subdivided to MCAO (middle cerebral artery occlusion), sham-operated (without MCAO) and intact (without any surgery) subgroups. After 24h, MCAO subgroups were subjected to 60 min of right MCAO. After 24 h reperfusion, neurologic deficit scores (NDS) were assessed in MCAO-operated subgroups. Immediately and 48 h after pretreatment, blood sampling were done for assessing level of serum TNF-α. The effect of intermittent and prolonged NBHO on EAATs expression level was also measured using western blotting. Result: Preconditioning with prolonged and intermittent NBHO decreased NDS and up-regulated EAAT1, EAAT2, and EAAT3, significantly. Also, oxygen exposure of prolonged and intermittent NBHO increased the level of serum TNF-α. Conclusion: Although further studies are needed to clarify the protective mechanisms OF hyperoxia, the intermittent and prolonged NBHO seems to partly exert their effects via increasing the serum level of TNF-α and upregulation of glutamate transporters. However, the intermittent NBHO seems to have appropriate effects with low toxicity.