Zinc: new clues to diverse roles in brain ischemia

摘要

Cerebral ischemia is a leading cause of morbidity and mortality, reflecting the extraordinary sensitivity of the brain to a brief loss of blood flow. A significant goal has been to identify neuronal injury pathways that are selectively activated following stroke and may be amenable to drug therapy. An important advance was made close to a quarter century ago, when Ca²⁺ overload was implicated as a critical link between glutamate excitotoxicity and ischemic neurodegeneration. However, early hope for effective therapies faded to frustration, as glutamate-targetted trials repeatedly failed to demonstrate efficacy in humans. In a review in 2000 in this journal, we described new evidence linking a related cation, zinc (Zn²⁺), to neuronal injury, emphasizing sources and mechanisms of Zn²⁺ toxicity. The current review highlights progress over the last decade, emphasizing mechanisms through which Zn²⁺ ions, from multiple sources, participate together with Ca²⁺ in different stages of ischemic injury cascades.