In the present study, our data showed that the knockdown of hippocampal NRSF did not affect the acute post-ischemic sensorimotor deficits after the MCAO surgery, but greatly attenuated diabetic ischemia-induced neuronal injury in hippocampus and improved learning/memory abilities, thus demonstrated that NRSF elevation in hippocampus plays an important role in the deterioration of ischemia-induced injury and hippocampus-dependent learning/memory impairment under diabetic/hyperglycemia condition. Here, REST is linked to ischemia.