Ischemic preconditioning inhibits expression of Na<SUP>+</SUP>/H<SUP>+</SUP> exchanger 1 (NHE1) in the gerbil hippocampal CA1 region after transient forebrain ischemia

초록

The participation of Na+/H+ exchanger (NHE) in neuronal damage/death in the hippocampal CA1 region (CA1) induced by transient forebrain ischemia has not been well established, although acidosis may be involved in neuronal damage/death. In the present study, we examined the effect of ischemic preconditioning (IPC) on NHE1 immunoreactivity following a 5 min of transient forebrain ischemia in gerbils. The animals used in the study were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+) shamoperated-group and IPC + ischemia-operated-group). IPC was induced by subjecting animals to 2 min of ischemia followed by 1 day of recovery. A significant neuronal loss was found in the stratum pyramidale (SP) of the CA1, not the CA2/3, of the ischemia-operated-group at 5 days post-ischemia. However, in the IPC + ischemia-operated-group, neurons in the SP of the CA1 were well protected. NHE1 immunoreactivity was not detected in any regions of the CA1-3 of the sham- and IPC + sham-operated-groups. However, the immunoreactivity was apparently expressed in the SP of the CA1-3 after ischemia, and the NHE1immunoreactivity was very weak 5 days after ischemia; however, at this point in time, strong NHE1 immunoreactivity was found in astrocytes in the CA1. In the CA2/3, NHE1 immunoreactivity was slightly changed, although NHE1 immunoreactivity was expressed in the SP. In the IPC + ischemia-operated-groups, NHE1 immunoreactivity was also expressed in the SP of the CA1-3; however, the immunoreactivity was more slightly changed than that in the ischemia-operated-groups. In brief, our findings show that IPC dramatically protected CA1 pyramidal neurons and strongly inhibited NHE1 expression in the SP of the CA1 after ischemia-reperfusion. These findings suggest that the inhibition of NHE1 expression may be necessary for neuronal survival from transient ischemic damage. (C) 2015 Elsevier B.V. All rights reserved.

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