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Natural killer (NK) cells exhibited decreased frequency and compromised function after acute stage of stroke, resulting in NK cell-associated immune deficiency and increased risk of infection. MicroRNAs (miRNAs) are post-transcriptional molecular modulators. Our previous study revealed a significant upregulation of miR-451a in circulating NK cells from patients with ischemic stroke, but its effects and precise mechanism on immune defense remain elusive. In this study, we observed a substantial elevation of miR-451a level in brain and splenic NK cells in murine model of ischemic stroke miR-451a mimics suppressed NK cell activation and cytotoxicity within the ischemic brain and periphery, including a downregulation of activation marker CD69, and reduced production of effector molecules IFN-\u03b3 and perforin. Conversely, miR-451a inhibitor preserved NK cell activation and cytotoxicity, rescuing local inflammation, and reducing bacterial burden in the lung. Pharmacological inhibition of Akt-mTOR pathway with AZD8055 effectively blocked the impacts of miR-451a on NK cell functions. Collectively, these findings suggest miR-451a negatively regulates NK cell cytotoxicity in both the brain and periphery, which could be re-addressed by modulating the Akt-mTOR signaling pathway.<\/jats:p>","DOI":"10.1177\/0271678x251321641","type":"journal-article","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T03:21:46Z","timestamp":1740194506000},"page":"1371-1384","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["The miR-451a facilitates natural killer cell-associated immune deficiency after ischemic stroke"],"prefix":"10.1177","volume":"45","author":[{"given":"Yan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuchen","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo-ran","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihe","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minshu","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Dong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"},{"name":"Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2196-9078","authenticated-orcid":false,"given":"Wei-Na","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,2,22]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000442015.53336.12"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61953-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/svn-2016-000025"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-302552"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-11-110"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00126-9"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)62456-9"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.144"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.02.015"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1765"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00968-1"},{"key":"e_1_3_3_13_2","doi-asserted-by":"crossref","first-page":"e079061","DOI":"10.1136\/bmj-2023-079061","article-title":"Colchicine in patients with acute ischaemic stroke or transient ischaemic attack (CHANCE-3): multicentre, double blind, randomised, placebo controlled trial","volume":"385","author":"Li J","year":"2024","unstructured":"Li J, Meng X, Shi FD, et\u00a0al. 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