{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:34:10Z","timestamp":1792787650484,"version":"4.5.0"},"reference-count":53,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"national natural science foundation of china","doi-asserted-by":"publisher","award":["82571493"],"award-info":[{"award-number":["82571493"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Outstanding Youth Project of Capital Medical University","award":["B2403"],"award-info":[{"award-number":["B2403"]}],"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Scientific and Technological Innovation 2030 of China-Major project","award":["2023ZD0505300, 2023ZD0505304"],"award-info":[{"award-number":["2023ZD0505300, 2023ZD0505304"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>Ischemic stroke triggers a profound inflammatory response that exacerbates secondary brain injury, with infiltrating macrophages serving as major pathological mediators. Although previous studies have largely focused on immune cell\u2013intrinsic mechanisms, the immunomodulatory role of cerebral endothelial cells in post-stroke inflammation remains poorly understood. In the current study, using single-cell RNA sequencing, we identified extensive inflammatory reprogramming in cerebral endothelial cells after stroke and discovered atypical chemokine receptor 1 (ACKR1) as a prominently upregulated regulator associated with chemokine sequestration and leukocyte recruitment. To determine its functional significance, we selectively overexpressed ACKR1 in cerebral endothelial cells using endothelial-targeted AAV-X1.1 in a mouse model of ischemic stroke. At 1 day after transient middle cerebral artery occlusion, endothelial ACKR1 overexpression preserved blood\u2013brain barrier integrity, evidenced by maintained ZO-1 continuity, enhanced pericyte and astrocytic endfoot coverage, and reduced leakage of both exogenous tracers and endogenous IgG. By day 3, ACKR1 overexpression markedly reduced macrophage infiltration, decreased infarct volume, and improved neurological outcomes. These protective effects persisted through day 28, accompanied by improved sensorimotor recovery and attenuated brain atrophy. Collectively, our findings identify cerebral endothelial cells as active regulators of post-stroke neuroinflammation and reveal endothelial ACKR1 signaling as a potential therapeutic strategy for ischemic stroke.<\/jats:p>","DOI":"10.1177\/0271678x261461872","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T07:28:37Z","timestamp":1781249317000},"page":"2561-2576","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Endothelial-specific ACKR1 overexpression attenuates macrophage infiltration and blood\u2013brain barrier disruption after ischemic stroke"],"prefix":"10.1177","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6178-5225","authenticated-orcid":false,"given":"Mengyuan","family":"Guo","sequence":"first","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Hypoxia Conditioning Translational Laboratory of Clinical Medicine, Chinese Institutes for Medical Research, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyi","family":"Fang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Hypoxia Conditioning Translational Laboratory of Clinical Medicine, Chinese Institutes for Medical Research, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyan","family":"Tang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Hypoxia Conditioning Translational Laboratory of Clinical Medicine, Chinese Institutes for Medical Research, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Shao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Hypoxia Conditioning Translational Laboratory of Clinical Medicine, Chinese Institutes for Medical Research, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6711-3841","authenticated-orcid":false,"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Hypoxia Conditioning Translational Laboratory of Clinical Medicine, Chinese Institutes for Medical Research, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunming","family":"Ji","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Hypoxia Conditioning Translational Laboratory of Clinical Medicine, Chinese Institutes for Medical Research, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China"},{"name":"Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.125.049864"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1917030"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.26867"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00642-1"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms27041700"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X231212377"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-025-01662-z"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12560"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.70072"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.109781"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaf026"},{"key":"e_1_3_4_13_2","first-page":"1254","article-title":"Estrogen and progesterone attenuate CD4-positive immune cell traffic to the penumbra region of rat\u2019s ischemic stroke brain","volume":"28","author":"Tamtaji A","year":"2025","unstructured":"Tamtaji A, Talaei SA, Naderian H, et al. Estrogen and progesterone attenuate CD4-positive immune cell traffic to the penumbra region of rat\u2019s ischemic stroke brain. Iran J Basic Med Sci 2025; 28: 1254\u20131260.","journal-title":"Iran J Basic Med Sci"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03206-4"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000004009"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH10-10-0662"},{"key":"e_1_3_4_17_2","first-page":"1","article-title":"The predictive value of serum CXCL2 and CXCL8 levels for early neurological deterioration in patients with penetrating artery disease-type ischemic stroke","volume":"2026","author":"Zhong Y","year":"2026","unstructured":"Zhong Y, Liu B. The predictive value of serum CXCL2 and CXCL8 levels for early neurological deterioration in patients with penetrating artery disease-type ischemic stroke. Int J Neurosci 2026; 2026: 1\u201311.","journal-title":"Int J Neurosci"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/cimb48030259"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.transci.2025.104255"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2024.0186"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-024-01025-5"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv124"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2026.104048"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1676988"},{"key":"e_1_3_4_25_2","article-title":"Reporting animal research: explanation and elaboration for the ARRIVE guidelines 2.0","volume":"18","author":"Percie du Sert N","year":"2020","unstructured":"Percie du Sert N, Ahluwalia A, Alam S, et al. Reporting animal research: explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biol 2020; 18: Article e3000411.","journal-title":"PLoS Biol"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.125.052213"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2300012120"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X231208993"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X19888630"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20925655"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38582-7"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1621174114"},{"key":"e_1_3_4_33_2","article-title":"Endothelial peroxiredoxin-4 is indispensable for blood\u2013brain barrier integrity and long-term functional recovery after ischemic stroke","volume":"121","author":"Xu N","year":"2024","unstructured":"Xu N, Jiang X, Zhang W, et al. Endothelial peroxiredoxin-4 is indispensable for blood\u2013brain barrier integrity and long-term functional recovery after ischemic stroke. Proc Natl Acad Sci U S A 2024; 121: Article e2400272121.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002111"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molpha.2025.100053"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1675"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj4922"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2025.06.009"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2026.104093"},{"key":"e_1_3_4_40_2","article-title":"Monocyte-derived macrophages and their roles in ischemic stroke","volume":"2026","author":"Dufort C","year":"2026","unstructured":"Dufort C, Tian Q, Lu L, et al. Monocyte-derived macrophages and their roles in ischemic stroke. J Cereb Blood Flow Metab 2026; 2026: 271678X251414082.","journal-title":"J Cereb Blood Flow Metab"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2024.148825"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.5607\/en.2016.25.5.241"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/nep3.70027"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2026.115450"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0335584"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2026.2662440"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X251359753"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X251318922"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0341005"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3544"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020412"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3666"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.07.004"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-024-01857-z"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X261461872","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0271678X261461872","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X261461872","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T08:48:27Z","timestamp":1791017307000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X261461872"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,5]]},"references-count":53,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1177\/0271678X261461872"],"URL":"https:\/\/doi.org\/10.1177\/0271678x261461872","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,5]]}}}