- We earlier reported that Zn²+ chelation improved recovery of synaptic potentials after transient oxygen and glucose deprivation in brain slices. Such an effect could be because of reduced accumulation of Zn²+ in postsynaptic neurons, or could also be due to prevention of the onset of spreading depression-like events. A combination of optical and electrical recording was used here to show that Zn²+ chelation is effective because it delays spreading depression-like events. If the duration of oxygen/glucose deprivation was sufficient to generate a spreading depression-like event, irrecoverable Ca²+-dependent loss of synaptic potentials occurred, regardless of Zn²+ availability. These results identify a key mechanism underlying protective effects of Zn²+ chelation, and emphasize the importance of evaluating spreading depression-like events in studies of neuroprotection.