{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:43:13Z","timestamp":1792773793919,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["ZD2022H001"],"award-info":[{"award-number":["ZD2022H001"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101409"],"award-info":[{"award-number":["82101409"]}],"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":["32071036"],"award-info":[{"award-number":["32071036"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In ischemic stroke (IS), the programmed death of neurons is a key factor contributing to poor prognosis and neurological dysfunction. Recently, it has been discovered that necroptosis, as a form of programmed cell death, promotes neuroinflammatory damage after IS; however, its mechanism is still unclear. Recent studies have shown that CCL11, as an eosinophil chemokine, may induce neuronal cytotoxicity by triggering the production of reactive oxygen species (ROS) in microglia. Meanwhile, CCR3, serving as the major functional membrane receptor target of CCL11, plays a crucial role in transducing CCL11 signals. This study establishes a mouse model of IS using permanent middle cerebral artery ligation (pMCAL) and utilizes methods such as Western blot (WB), quantitative polymerase chain reaction (qPCR), and immunofluorescence (IF) to detect changes in necroptosis markers and chemokines. The aim was to analyze the dynamic progression of necroptosis after stroke and its potential regulatory mechanisms. In in\u00a0vivo experiments, the recovery levels of necroptosis and neuroinflammation were observed by administering a C\u2010C motif chemokine receptor 3 (CCR3) inhibitor via cerebral stereotaxic injection. In\u00a0vitro experiments utilized an oxygen\u2013glucose deprivation (OGD) model to simulate the in\u00a0vivo ischemic state of astrocytes. Exogenous CCL11 was administered, and the expression of CCR3 on astrocytes was inhibited to observe changes in necroptosis and apoptosis markers, including receptor\u2010interacting protein kinase 1 (RIPK1), receptor\u2010interacting protein kinase 1 (RIPK3), and mixed lineage kinase domain\u2010like protein (MLKL), as well as inflammatory factors interleukin\u20101 beta (IL\u20101\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ), NOD\u2010like receptor thermal protein domain\u2010associated protein 3 (NLRP3), and apoptosis\u2010associated speck\u2010like protein containing a CARD(ASC). The results indicated that CCL11 stimulation significantly activated necroptosis and apoptosis in astrocytes, while blocking the CCR3 receptor on astrocytes resulted in a significant inhibition of this process. By collecting supernatants from various groups of astrocytes and stimulating neurons, it was further observed that necroptosis, induced by CCL11\u2010CCR3 stimulation, significantly disrupts synaptic connections in neurons. We conclude that the CCL11\u2010CCR3 axis plays a key role in the necroptosis of astrocytes after IS.\n                  <\/jats:p>","DOI":"10.1096\/fj.202502723rr","type":"journal-article","created":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T11:26:19Z","timestamp":1766661979000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The\n                    <scp>CCL11<\/scp>\n                    \u2010\n                    <scp>CCR3<\/scp>\n                    Axis Regulates the Aggravation of Neuroinflammation in Astrocytic Necroptosis After Cerebral Ischemia"],"prefix":"10.1096","volume":"40","author":[{"given":"Han","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Heilongjiang Provincial Key Laboratory of Neurobiology Harbin Medical University  Harbin People's Republic of 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