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Zinc is an essential trace element that plays important physiological roles in the central nervous system. Free zinc concentration is tightly regulated by zinc-related proteins in the brain under normal conditions. Disruption of zinc homeostasis, however, has been found to play an important role in the mechanism of brain injury following ischemic stroke. A large of free zinc releases from storage sites after cerebral ischemia, which affects the functions and survival of nerve cells, including neurons, astrocytes, and microglia, resulting in cell death. Ischemia-triggered intracellular zinc accumulation also disrupts the function of blood\u2013brain barrier via increasing its permeability, impairing endothelial cell function, and altering tight junction levels. Oxidative stress and neuroinflammation have been reported to be as major pathological mechanisms in cerebral ischemia\/reperfusion injury. Studies have showed that the accumulation of intracellular free zinc could impair mitochondrial function to result in oxidative stress, and form a positive feedback loop between zinc accumulation and reactive oxygen species production, which leads to a series of harmful reactions. Meanwhile, elevated intracellular zinc leads to neuroinflammation. Recent studies also showed that autophagy is one of the important mechanisms of zinc toxicity after ischemic injury. Interrupting the accumulation of zinc will reduce cerebral ischemia injury and improve neurological outcomes. This review summarizes the role of zinc toxicity in cellular and tissue damage following cerebral ischemia, focusing on the mechanisms about oxidative stress, inflammation, and autophagy.<\/jats:p>","DOI":"10.1093\/mtomcs\/mfae012","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T06:17:01Z","timestamp":1709187421000},"source":"Crossref","is-referenced-by-count":20,"title":["Contribution of zinc accumulation to ischemic brain injury and its mechanisms about oxidative stress, inflammation, and autophagy: an update"],"prefix":"10.1093","volume":"16","author":[{"given":"Xueqi","family":"Yang","sequence":"first","affiliation":[{"name":"Institute of Cerebrovascular Disease Research, Xuanwu Hospital of Capital Medical University , 45 Changchun Street, Beijing 100053 , China"},{"name":"Beijing Geriatric Medical Research Center , Beijing 100053 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Cerebrovascular Disease Research, Xuanwu Hospital of Capital Medical University , 45 Changchun Street, Beijing 100053 , China"},{"name":"Beijing Geriatric Medical Research Center , Beijing 100053 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Ding","sequence":"additional","affiliation":[{"name":"Institute of Cerebrovascular Disease Research, Xuanwu Hospital of Capital Medical University , 45 Changchun Street, Beijing 100053 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Renaissance School of Medicine, Stony Brook University , Stony Brook, NY 11794 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifeng","family":"Qi","sequence":"additional","affiliation":[{"name":"Institute of Cerebrovascular Disease Research, Xuanwu Hospital of Capital Medical University , 45 Changchun Street, Beijing 100053 , China"},{"name":"Beijing Geriatric Medical Research Center , Beijing 100053 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Cerebrovascular Disease Research, Xuanwu Hospital of Capital Medical University , 45 Changchun Street, Beijing 100053 , China"},{"name":"Beijing Geriatric Medical Research Center , Beijing 100053 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"issue":"1","key":"2024032013593692000_bib1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1021\/pr050361j","article-title":"Counting the zinc-proteins encoded in the human genome","volume":"5","author":"Andreini","year":"2006","journal-title":"J. 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