Focal
cerebral ischemia can impair the induction of activity-dependent long-term potentiation (LTP) in the hippocampus. This impairment of hippocampal synaptic plasticity can be caused by excitotoxicity and subsequent perturbation of hippocampal LTP-relevant transmitter systems, which include NR2B and PSD-95. It has been suggested that hyperpolarization-activated
cyclic-nucleotide-gated (HCN) channels may play an important role in the control of membrane excitability and rhythmic neuronal activity. Our previous study has indicated that the selective HCN channel blocker
ZD7288 can produce a dose-dependent inhibition of the induction of LTP at the Schaffer collateral-CA1 synapse of hippocampus by reducing the amount of
glutamate released. It has also been demonstrated that
ZD7288 can protect against neuronal injury caused by
oxygen glucose deprivation. In the present study, we investigated the effect of
ZD7288 on the induction of activity-dependent LTP and the expression of NR2B and PSD-95 after focal
cerebral ischemia/
reperfusion injury. The results showed that the induction of LTP was significantly impaired and the levels of NR2B and PSD-95
mRNA and
protein were markedly decreased in the CA1 region of hippocampus following focal
cerebral ischemia/
reperfusion injury. Administration of low dose
ZD7288 (0.25 μg) at 30 min and 3 h after the onset of
ischemia attenuated the impairment of LTP induction and alleviated the NR2B and PSD-95
mRNA and
protein down-regulation commonly induced by
cerebral ischemia/
reperfusion injury. These results suggest that low dose
ZD7288 can ameliorate the
ischemia/reperfusion-induced impairment of synaptic plasticity in the hippocampal CA1 region.