In this study, utilizing cellular and animal models of ischemic stroke, including transgenic mice with ZnT3 specifically knockout in neurons, we determined whether ECF-Zn contributes to BBB damages during cerebral ischemia, and investigated both the source of high levels of ECF-Zn and the mechanism by which ECF-Zn mediates ischemia-induced BBB damage. The gene discussed is SLC30A3; the disease is ischemia.