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

Abstract

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 5min 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 (+) sham-operated-group and IPC+ischemia-operated-group). IPC was induced by subjecting animals to 2min of ischemia followed by 1day 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 5days 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 5days after ischemia; however, at this point in time, strong NHE1immunoreactivity was found in astrocytes in the CA1. In the CA2/3, NHE1immunoreactivity was slightly changed, although NHE1immunoreactivity 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.