en Neurophysiology/Pharmacology Neurophysiology/Pharmacology Experimental research article Experimental research article Introduction: The purpose of this study was to determine Na-Ca exchanger 2, 3 (NCX2, 3) protein level changes during 2, 5, 10, 15 days after induction of normobaric hyperoxia (HO) preconditioning. Materials and Methods: Rats were divided in two experimental groups. The first group was exposed to 95% inspired HO for 4 h/day for 6 consecutive days (HO). The second group acted as control, and was exposed to 21% oxygen in the same chamber. Each main group was subdivided to middle cerebral artery occlusion (MCAO-operated) and intact (without any surgery) subgroups. After 2, 5, 10 and 15 days from pretreatment, MCAO-operated subgroups were subjected to 60 min of right MCAO. After 24 hours reperfusion, neurologic deficit score (NDS) and infarct volume (IV) were measured in MCAO-operated subgroups. The NCX 2, 3 expression levels of core, penumbra and subcortex regions were assessed in sham-operated and intact subgroups. Results: Expression of NCX 2, 3 proteins were increased in penumbra (P=0.000, P=0.002), core (P=0.001, P=0.033) and just NCX3 was increased in subcortex (P=0.033) during preconditioning with HO. Neurologic deficit score and infarct volume were decreased with HO preconditioning. These effects of hyperoxia disappeared gradually during 15 days after pretreatment. Conclusion: Although further studies are needed to clarify the mechanisms of time course of neuroprotection, HO durable effects on NCX2, 3 expression, IV and NDS are consistent with an active role in the genesis of ischemic neuroprotection. hyperoxia, brain ischemia tolerance, neuroprotection, NCX2, NCX3 76 89 http://ppj.phypha.ir/browse.php?a_code=A-10-29-6&slc_lang=en&sid=1 Ekram Mohammadi ekram.mohammadi@yahoo.com 3200319475328460015293 3200319475328460015293 No Shahid Beheshti University Mohammad Reza Bigdeli bigdelimohammadreza@yahoo.com 3200319475328460015294 3200319475328460015294 Yes Shahid Beheshti University