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Here we evaluated the role of EAAC1 in neuronal resistance to ischemia.<jats:italic>EAAC1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice subjected to transient cerebral ischemia exhibited twice as much hippocampal neuronal death as wild-type mice and a corresponding increase in microglial activation.<jats:italic>EAAC1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice also had elevated vesicular and cytosolic zinc concentrations in hippocampal CA1 neurons and an increased zinc translocation to postsynaptic neurons after ischemia. Treatment of the<jats:italic>EAAC1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice with<jats:italic>N<\/jats:italic>-acetyl cysteine restored neuronal glutathione concentrations and normalized basal zinc levels in the<jats:italic>EAAC1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice. Treatment of the<jats:italic>EAAC1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice with either<jats:italic>N<\/jats:italic>-acetyl cysteine or with zinc chelators reduced ischemia-induced zinc translocation, superoxide production, and neuron death. These findings suggest that cysteine uptake by EAAC1 is important for zinc homeostasis and neuronal antioxidant function under ischemic conditions.<\/jats:p>","DOI":"10.1523\/jneurosci.2084-10.2010","type":"journal-article","created":{"date-parts":[[2010,11,17]],"date-time":"2010-11-17T19:25:03Z","timestamp":1290021903000},"page":"15409-15418","source":"Crossref","is-referenced-by-count":43,"title":["EAAC1 Gene Deletion Alters Zinc Homeostasis and Exacerbates Neuronal Injury after Transient Cerebral Ischemia"],"prefix":"10.1523","volume":"30","author":[{"given":"Seok Joon","family":"Won","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Hoon","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M.","family":"Brennan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung 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