Inhibition of EphA4 signaling after ischemia-reperfusion reduces apoptosis of CA1 pyramidal neurons.

Hippocampal CA1 pyramidal neurons are sensitive to ischemic damage. However, the cellular and molecular mechanisms underlying neuronal cell death caused by ischemia-reperfusion (I/R) are not completely clear. Here, we report that the ephrinA/EphA cell-cell interaction signaling pathway plays an important role in the apoptosis of hippocampal CA1 pyramidal neurons induced by I/R. We found that the expression of ephrinA3 and EphA4 is increased in the CA1 region following transient forebrain ischemia. Blocking ephrinA3/EphA4 interaction by EphA4-Fc, an inhibitor of EphA4, attenuated apoptotic neuronal cell death, likely through the inhibition of caspase-3 activation. These results reveal a novel function of ephrin/Eph signaling in the regulation of apoptosis in CA1 pyramidal neurons after I/R.