Abstract

Introduction: Recent studies suggest that sublethal ischemia and intermittent normobaric hyperoxia (InHO) protect the brain from subsequent ischemic injury. In this, changes in the expression of excitatory amino-acid transporters (EAATs) and tumor necrosis factor-a converting enzyme (TACE) may play a role. We sought to identify and clarify the nature of any such changes. Method: Rats were divided into 3 experimental groups, each of 15 animals. The first group was exposed to normobaric hyperoxia (fractional inspired oxygen concentration 95) for 4 hours/day for 6 consecutive days (InHO). The second group acted as controls, and was exposed to 21 oxygen in the same chamber (room air). The third group acted as a model of ischemic preconditioning, and was exposed to 21 oxygen in the same chamber and subjected to 10 minutes of temporary middle cerebral artery (MCA) occlusion (tMCAO). After 24 hours, 9 animals from each group were subjected to 60 minutes of right MCA occlusion (MCAO). After 24 hours of reperfusion, neurologic deficit score and infarct volume were assessed in MCAO-operated subgroups. The remaining 6 animals in each group remained intact and, 48 hours after pretreatment, were killed for assessment of EAATs and TACE expression in the ipsilateral hemisphere. Results: Preconditioning with InHO and tMCAO decreased neurologic deficit score and infarct volume, and increased expression of EAAT1, EAAT2, EAAT3, and TACE. Conclusion: InHO and tMCAO are associated with expression of EAAT1, EAAT2, EAAT3, and TACE, consistent with an active role in the genesis of ischemic protection.