Detection of pathological zinc accumulation in neurons: Methods for autopsy, biopsy, and cultured tissue

It has been repeatedly shown that synaptically released zinc contributes to excitotoxic neuronal injury in ischemia, epilepsy, and mechanical head tra uma. Such zinc-induced injury leaves an unmistakable "footprint" in the inj ured neurons, allowing an easy and unambiguous postmortem diagnosis. This f ootprint is the presence of weakly bound, histochemically reactive zinc in the cytoplasm of the perikaryon and proximal dendrites. Such staining appea rs to be a necessary and sufficient marker for zinc-induced neuronal injury . Here we show how to prepare and stain tissue from biopsy, autopsy, or exp erimental animal sources for maximal contrast and visibility of zinc-injure d neurons.