Selective loss of cytosolic Zn2+ accumulation as a result of TRPM2 deficiency also attenuated ROS production during reperfusion (Supplementary Figure 7) and potent neuronal protection (Figures 2, 3, 4, 5), and provided compelling evidence to suggest TRPM2 activation during reperfusion is a key step initiating a vicious positive feedback mechanism driving the delayed increase in the [Zn2+]c and cell death in CA1 pyramidal neurons and memory impairments after transient ischemia. The gene discussed is TRPM2; the disease is memory impairment.