Excess release of chelatable zinc (Zn2+) from central synaptic vesicles may contribute to the pathogenesis of selective neuronal cell death following transient forebrain ischemia, but a role in neurodegeneration after focal ischemia has not been defined. Adult male Long-Evans rats subjected to middle cerebral artery occlusion (MCAO) for 30 min followed by reperfusion developed delayed cerebral infarction reaching completion 3 days after the insult. One day after the insult, many degenerating cerebral neurons exhibited increased intracellular Zn2+, and some labeled with the antibody against activated caspase-3. I.c.v. administration of the Zn2+ chelator, EDTA saturated with equimolar Ca2+ (CaEDTA), 15 min prior to ischemia attenuated subsequent Zn2+ translocation into cortical neurons, and reduced infarct volume measured 3 days after ischemia. Although the protective effect of CaEDTA at this endpoint was substantial (about 70% infarct reduction), it was lost when insult severity was increased (from 30 to 60 min MCAO), or when infarct volume was measured at a much later time point (14 days instead of 3 days after ischemia). These data suggest that toxic Zn2+ translocation, from presynaptic terminals to post-synaptic cell bodies, may accelerate the development of cerebral infarction following mild transient focal ischemia.

Original languageEnglish
Pages (from-to)871-878
Number of pages8
Issue number3
StatePublished - Dec 9 2002


  • CaEDTA
  • Neuroprotection
  • Neurotoxicity
  • Rat
  • Stroke
  • Transition metals


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