{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T01:07:01Z","timestamp":1789780021724,"version":"4.0.1"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M744023"],"award-info":[{"award-number":["2023M744023"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024B1515020021"],"award-info":[{"award-number":["2024B1515020021"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171307"],"award-info":[{"award-number":["82171307"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971110"],"award-info":[{"award-number":["81971110"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Monocyte\u2010derived macrophages and microglia initially adopt an anti\u2010inflammatory phenotype following stroke but later transition to a pro\u2010inflammatory state. The mechanisms underlying this phenotypic shift remain unclear. This study investigates the activation dynamics of molecular signaling pathways in macrophages and microglia after stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We utilized publicly available single\u2010cell RNA sequencing datasets to examine the activation dynamics of molecular signaling pathways alongside the pro\u2010inflammatory phenotype of macrophages and microglia. Male C57BL\/6 mice underwent transient middle cerebral artery occlusion (tMCAO), with the STING inhibitor H151 administered to tMCAO mice. Neurobehavioral performance was assessed using rotarod, foot fault, novel object recognition, and water maze tests at 5\u2010, 7\u2010, 10\u2010, and 14\u2010days post\u2010stroke. Primary microglia and bone marrow\u2010derived macrophages were cultured for in\u00a0vitro experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Single\u2010cell sequencing data indicated that the activation of STING and subsequent type I interferon signaling drove the phenotypic shift of microglia and macrophages toward a pro\u2010inflammatory state in the stroke lesion. Immunostaining demonstrated that the emergence of pro\u2010inflammatory microglia and macrophages aligned with the activation time course of STING and type I interferon signaling. Continuous phagocytosis by macrophages and microglia led to STING activation, which triggered type I interferon signaling and promoted the phenotypic shift. Inhibition of STING signaling prevented this transition, reduced neuroinflammation, and conferred protection against ischemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings elucidated the critical role of STING\u2010mediated type I interferon signaling in driving post\u2010stroke neuroinflammation and underscored the potential of STING inhibition as a therapeutic strategy for alleviating neuroinflammatory responses following stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70106","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T04:41:16Z","timestamp":1734583276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["<scp>STING<\/scp>\n                    Activation in Macrophages and Microglia Drives Poststroke Inflammation: Implications for Neuroinflammatory Mechanisms and Therapeutic Interventions"],"prefix":"10.1111","volume":"30","author":[{"given":"Zhiruo","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Brain Function and Disease  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shisi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmei","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2118-0368","authenticated-orcid":false,"given":"Zhengqi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Brain Function and Disease  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Brain Function and Disease  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03762-2"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-022-00943-7"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-021-00887-4"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.11.041"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07317"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.659656"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000226980.95389.0b"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2009.09.010"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.207"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0244-x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36132-9"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2116833"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0287-8"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00666-9"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-022-00337-2"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.04.022"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-019-00694-y"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI87532"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1557-6"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.70106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T02:36:49Z","timestamp":1736735809000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.70106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":19,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/cns.70106"],"URL":"https:\/\/doi.org\/10.1111\/cns.70106","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"2024-07-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70106"}}