In Vivo Measurement of Presynaptic Zn²⁺ Release during Forebrain Ischemia in Rats

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Previous studies have suggested that during forebrain ischemia, considerable Zn²⁺ is released from synaptic vesicles of gultamatergic neuronal terminals and accumulates in hippocampal CA1 pyramidal neurons, leading to delayed neuronal death. However, since a time lag exists between the accumulation of Zn²⁺ and the occurrence of ischemia and there are conflicting reports about the amount of Zn²⁺ released, the level of released Zn²⁺ during ischemia in vivo is still unclear. In this study, we investigated the temporal change of extracellular Zn²⁺ in the hippocampal CA1 area using microdialysis and the accumulation of Zn²⁺ in hippocampal CA1 neurons with TSQ staining in rats with a transient forebrain ischemia. The level of extracellular Zn²⁺ in the CA1 area increased transiently reaching a peak 15 min after occlusion, then decreased with time, returning to the basal level 15 min after reperfusion. In addition, at this peak, the level of extracellular Zn²⁺ was about twice the basal level. Assessment of the intracellular Zn²⁺ in hippocampal neurons with TSQ revealed that Zn²⁺ accumulate at 24 h, but not 0 and 6 h after ischemia. These results suggest that, although the synaptic vesicular Zn²⁺ is released into the synaptic cleft during ischemia in vivo, the amount of released Zn²⁺ might not be so excessive, and it does not accumulate in hippocampal CA1 pyramidal neurons immediately after ischemia.