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However, the reversibility and translational potential of PS exposure in damaged cells after stroke are still unknown. Here, we demonstrated that plasma Annexin V, which has a high affinity to membranes bearing PS, was increased in patients with salvage penumbra after endovascular therapy, and associated with early neurological improvement. Moreover, Annexin V treatment could decrease PS exposure and mitigate neurological impairments in transient ischemia\/reperfusion mouse models, but not in permanent ischemia. Furthermore, we used a combination of cell, rodent, and nonhuman primate ischemia\/reperfusion models and found that transmembrane protein 30A (Tmem30a) was increased in the ischemic penumbra after stroke and imperative for less PS exposure and better neurological functions. Mechanistically, mitigation of PS exposure mediated by Tmem30a\/Annexin V connection led to decreased expression of apoptosis and necroptosis markers in neurons of penumbra. Overall, our findings reveal a previously unappreciated role of reducing PS exposure by Annexin V treatment in protecting the penumbra in a clinically relevant ischemia\/reperfusion model. Tmem30a is essential for reducing PS exposure in the penumbra after ischemic stroke.<\/jats:p>","DOI":"10.1002\/mco2.70140","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T07:55:13Z","timestamp":1742284513000},"source":"Crossref","is-referenced-by-count":4,"title":["Mitigating Early Phosphatidylserine Exposure in a Tmem30a\u2010Dependent Way Ameliorates Neuronal Damages After Ischemic Stroke"],"prefix":"10.1002","volume":"6","author":[{"given":"Chuanjie","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Neurology and China\u2010America Institute of Neuroscience Beijing Institute of Geriatrics Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology and China\u2010America Institute of Neuroscience Beijing Institute of Geriatrics Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Neurology and China\u2010America Institute of Neuroscience Beijing Institute of Geriatrics Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine  Beijing China"},{"name":"Center of Stroke Beijing Institute for Brain Disorders Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachen","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology and China\u2010America Institute of Neuroscience Beijing Institute of Geriatrics Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaili","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology and China\u2010America Institute of Neuroscience Beijing Institute of Geriatrics Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiyou","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Stroke Beijing Institute for Brain Disorders Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center of Stroke Beijing Institute for Brain Disorders Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianjun","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine Center for Medical Genetics Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunming","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Neurology and China\u2010America Institute of Neuroscience Beijing Institute of Geriatrics Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine  Beijing China"},{"name":"Center of Stroke Beijing Institute for Brain Disorders Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology and China\u2010America Institute of Neuroscience Beijing Institute of Geriatrics Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine  Beijing China"},{"name":"Center of Stroke Beijing Institute for Brain Disorders Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2953"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0002-2"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2016.04.004"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18928"},{"issue":"2","key":"e_1_2_10_6_1","first-page":"S126","article-title":"Indications for Mechanical Thrombectomy for Acute Ischemic Stroke: Current Guidelines and Beyond","volume":"97","author":"Jadhav A. 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