Time course of normobaric hyperoxia preconditioning on NCX2, 3 expression

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. Abbreviation: ANOVA: analysis of variance; BBB: blood brain barrier; EAAT: excitatory amino acid transporter; EDTA: ethylenediaminetetraacetic acid; HO: normobaric hyperoxia; I: intact; I-HO: intact normobaric hyperoxia subgroup; I-RA: intact normobaric normoxia subgroup; IT: ischemic tolerance; LSD: least significant difference; MCA: middle cerebral artery; MCAO: middle cerebral artery occlusion; NCX: Na+-Ca2+exchanger; NDS: neurologic deficit score; NF-kB: nuclear factor- kappa B; O-HO: MCAO-operated normobaric hyperoxia subgroup; O-RA: MCAO-operated normobaric normoxia subgroup; P38MAPK: p38 mitogen-activated protein kinase; PVDF: polyvinylidenedifluoride; RA: room air (normobaric normoxia); S: sham; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis; SEM: standard error of mean; TNF-alpha: tumour necrosis factor- alpha