Hypoxic preconditioning induces neuroprotection against transient global ischemia in adult rats via preserving the activity of Na+/K+-ATPase

We demonstrated previously that 30 min of hypoxic preconditioning (HPC) applied 1 day before 10 min of transient global cerebral ischemia (tGCI) reduced neuronal loss in the hippocampal CA1 subregion in adult rats. The aim of the present study was to investigate the role of Na+/K+-ATPase and protein kinase Mζ (PKMζ) in the protective effect of HPC against tGCI in adult rats. We found that the activity of Na+/K+-ATPase decreased in the hippocampal CA1 subregion after 10 min of tGCI. This effect was not seen after 30 min of HPC in adult rats. Corresponding to the changes in Na+/K+-ATPase activity, the surface expression of Na+/K+-ATPase α1 subunit increased after HPC. Furthermore, HPC dramatically reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells in the hippocampal CA1 subregion after tGCI. However, neither PKMζ nor phosphorylation of PKMζ was changed after tGCI or HPC. The results of the present study are consistent with the hypothesis that both enhanced recovery of Na+/K+-ATPase activity due to preserved the protein levels of Na+/K+-ATPase α1 subunit and reduced DNA fragmentation after tGCI contribute to the protection afforded by HPC. However, PKMζ activation does not appear to play a role in this neuroprotection.

► HPC preserved the activity of Na+/K+-ATPase in the CA1 region after 10 min of tGCI.
► HPC increased the surface expression of Na+/K+-ATPase α1 subunit after 10 min of tGCI.
► HPC reduced TUNEL-positive cells in the hippocampal CA1 region after 10 min of tGCI.
► Neither PKMζ nor phosphorylation of PKMζ was changed after ischemia or HPC.