Although
acidosis may be involved in neuronal death, the participation of
Na(+)/H(+) exchanger (NHE) in delayed neuronal death in the hippocampal CA1 region induced by transient forebrain
ischemia has not been well established. In the present study, we investigated the chronological alterations of NHE1 in the hippocampal CA1 region using a gerbil model after
ischemia/reperfusion. In the
sham-operated group, NHE1 immunoreactivity was weakly detected in the CA1 region. Two and 3 days after
ischemia/reperfusion, NHE1 immunoreactivity was observed in glial components, not in neurons, in the CA1 region. Four days after
ischemia/reperfusion, NHE1 immunoreactivity was markedly increased in CA1 pyramidal neurons as well as glial cells. These glial cells were identified as astrocytes based on double immunofluorescence staining. Western blot analysis also showed that NHE
protein level in the CA1 region began to increase 2 days after
ischemia/reperfusion. The treatment of 10 mg/kg 5-(N-ethyl-N-isopropyl)
amiloride, a NHE inhibitor, significantly reduced the
ischemia-induced hyperactivity 1 day after
ischemia/reperfusion. In addition, NHE inhibitor potently protected CA1 pyramidal neurons from ischemic damage, and NHE inhibitor attenuated the activation of astrocytes and microglia in the ischemic CA1 region. In addition, NHE inhibitor treatment blocked
Na(+)/Ca(2+) exchanger 1 immunoreactivity in the CA1 region after transient forebrain
ischemia. These results suggest that NHE1 may play a role in the delayed death, and the treatment with NHE inhibitor protects neurons from ischemic damage.