{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:39:55Z","timestamp":1791484795440,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92368105"],"award-info":[{"award-number":["92368105"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The mechanisms underlying meningeal lymphatic vessel (mLV)-mediated immune cell clearance after stroke remain unclear. Using a mouse middle cerebral artery occlusion model, we performed single-cell RNA sequencing to analyze post-ischemic meningeal macrophages. In vitro co-culture and CCR2 inhibition (RS504393) validated the CCL2-CCR2 axis between lymphatic endothelial cells and macrophages. Macrophage trafficking to mLVs and cervical lymph nodes was assessed by Evans Blue tracing and F4\/80 immunofluorescence. We utilized VEGF-C to enhance meningeal lymphatic vessel function and concomitantly evaluated neurological deficits, brain edema, and neuroinflammation. Ischemia expanded meningeal macrophages, whose crosstalk with lymphatic endothelial cells relied on CCL2-CCR2 axis. CCR2 inhibition impaired macrophage trafficking to mLVs and cervical lymph nodes, worsening edema, motor deficits, and inflammation, whereas VEGF-C enhanced mLV drainage and improved outcomes. We identify a novel mechanism where in mLVs recruit macrophages via CCL2 for perivascular clearance post-ischemia. Combining VEGF-C with modulation of the CCL2-CCR2 axis presents a promising synergistic therapeutic strategy for stroke.<\/jats:p>","DOI":"10.3390\/cimb48030259","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T14:06:56Z","timestamp":1772460416000},"page":"259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Meningeal Lymphatics Drives Macrophage Clearance via CCL2-CCR2 Axis After Cerebral Ischemia"],"prefix":"10.3390","volume":"48","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1001\/jama.2015.3058","article-title":"Acute stroke intervention: A systematic review","volume":"313","author":"Prabhakaran","year":"2015","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s12975-019-00694-y","article-title":"Functional Dynamics of Neutrophils After Ischemic Stroke","volume":"11","author":"Cai","year":"2020","journal-title":"Transl. 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