Preconditioning with Sublethal Ischemia or Intermittent Normobaric Hyperoxia Up-regulates Glutamate Transporters and Tumor Necrosis Factor-α Converting Enzyme in the Rat Brain

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-α 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.

Key Words: Normobaric hyperoxia, brain ischemia tolerance, stroke, neuroprotection, glutamate transporter, tumor necrosis factor-α converting enzyme