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" Rapid Intramitochondrial Zn2+ Accumulation in CA1 Hippocampal Pyramidal Neurons After Transient Global Ischemia: "
Yin, Hong Z; Wang, Hwai-Lee; Ji, Sung G; Medvedeva, Yuliya V; Tian, Guilian; Bazrafkan, Afsheen K; Maki, Niki Z; Akbari, Yama; Weiss, John H
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AL
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| Record Number
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909371
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LA8x75m5cn
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| Title & Author
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Rapid Intramitochondrial Zn2+ Accumulation in CA1 Hippocampal Pyramidal Neurons After Transient Global Ischemia:. A Possible Contributor to Mitochondrial Disruption and Cell Death. [Article]\ Yin, Hong Z; Wang, Hwai-Lee; Ji, Sung G; Medvedeva, Yuliya V; Tian, Guilian; Bazrafkan, Afsheen K; Maki, Niki Z; Akbari, Yama; Weiss, John H
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2019
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| Title of Periodical
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UC Irvine
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| Abstract
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Mitochondrial Zn2+ accumulation, particularly in CA1 neurons, occurs after ischemia and likely contributes to mitochondrial dysfunction and subsequent neurodegeneration. However, the relationship between mitochondrial Zn2+ accumulation and their disruption has not been examined at the ultrastructural level in vivo. We employed a cardiac arrest model of transient global ischemia (TGI), combined with Timm's sulfide silver labeling, which inserts electron dense metallic silver granules at sites of labile Zn2+ accumulation, and used transmission electron microscopy (TEM) to examine subcellular loci of the Zn2+ accumulation. In line with prior studies, TGI-induced damage to CA1 was far greater than to CA3 pyramidal neurons, and was substantially progressive in the hours after reperfusion (being significantly greater after 4- than 1-hour recovery). Intriguingly, TEM examination of Timm's-stained sections revealed substantial Zn2+ accumulation in many postischemic CA1 mitochondria, which was strongly correlated with their swelling and disruption. Furthermore, paralleling the evolution of neuronal injury, both the number of mitochondria containing Zn2+ and the degree of their disruption were far greater at 4- than 1-hour recovery. These data provide the first direct characterization of Zn2+ accumulation in CA1 mitochondria after in vivo TGI, and support the idea that targeting these events could yield therapeutic benefits.
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