Zn²+ chelation improves recovery by delaying spreading depression-like events.
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.
Carter
Russell E
RE
Department of Neurosciences, University of New Mexico, Albuquerque, New Mexico, USA.
Weiss
John H
JH
Shuttleworth
C William
CW
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology* / Q000627:therapeutic use; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009924:Organ Culture Techniques; D015032:Zinc / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000633:toxicity
D002614:Chelating Agents; D018696:Neuroprotective Agents; D015032:Zinc