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Metal Ion in Stroke pp 209–226Cite as

Zinc in Stroke: Time for a New Approach?

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Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

For centuries, stroke has been a leading cause of morbidity and mortality, especially in developed countries. Substantial evidence supports the hypothesis that neural cell death occurring for days or weeks after the initial blockage or hemorrhage is the result of an excitotoxic cascade involving metal ions, especially calcium. Unfortunately, scores of drugs designed to interdict the cascade and shown to be neuroprotective in animal models have failed in human trials, suggesting our understanding is incomplete. Evidence is reviewed here that zinc is a potent toxin released from cellular sites during and after ischemia that can cripple the cell’s energy production and ability to defend itself from the well-known effects of oxidative stress. In particular, the protonation of histidinyl zinc ligands due to lactic acidosis and the oxidation of thiol ligands both can release bound intracellular zinc irrespective of any channel opening, and zinc has been shown to be a potent inhibitor of mitochondrial enzymes involved in energy production and the destruction of reactive oxygen species. There is disagreement as to whether elevated zinc ion levels induce apoptosis. These results suggest that zinc ion may play a substantial role in the toxic events following stroke, and may suggest alternative therapies.

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Acknowledgments

The author would like to thank Gary Fiskum, Chris Frederickson, and Abraham Brown for fruitful discussions, and the National Institutes of Health (RO1 EB03924) for support.

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  1. Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Richard B. Thompson PhD

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  1. , Department of Biomedical Sciences, Ohio University, 346 Irvine Hall, Athens, 45701, Ohio, USA

    Yang V. Li

  2. Loma Linda University, 11234 Anderson Street, Room 2562B, Loma Linda, 92354, California, USA

    John H. Zhang

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Thompson, R.B. (2012). Zinc in Stroke: Time for a New Approach?. In: Li, Y., Zhang, J. (eds) Metal Ion in Stroke. Springer Series in Translational Stroke Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9663-3_9

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