{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:27:02Z","timestamp":1786688822981,"version":"build-2736575974"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS202400356146 , 2021R1A2C2010219, RS202522872969"],"award-info":[{"award-number":["RS202400356146 , 2021R1A2C2010219, RS202522872969"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004332","name":"Seoul National University Hospital","doi-asserted-by":"publisher","award":["0620210740, 0720253165"],"award-info":[{"award-number":["0620210740, 0720253165"]}],"id":[{"id":"10.13039\/501100004332","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Subarachnoid hemorrhage (SAH) remains a devastating cerebrovascular disease with limited therapies targeting secondary neurological injury. Increasing evidence suggests that the early brain injury (EBI) period within the first 72h after SAH represents a critical therapeutic window characterized by diffuse neurovascular and inflammatory activation within the cerebrospinal fluid (CSF) and meningeal compartments. Although resident microglial responses during EBI have been extensively investigated, the contribution of infiltrating CCR2-dependent monocytes to inflammatory amplification and secondary neuronal injury during this acute phase remains incompletely defined. Here, we investigated the temporal role of CCR2-dependent monocyte recruitment during EBI following experimental SAH. Using a murine endovascular perforation model, we evaluated outcomes in CCR2-deficient mice and wild-type mice treated with a pharmacologic CCR2 antagonist at distinct post-SAH timepoints. CCR2 deletion or early pharmacologic inhibition significantly reduced Ly6C\n                    <jats:sup>hi<\/jats:sup>\n                    monocyte infiltration during EBI, attenuated CSF TNF\u03b1 and IL-6 levels, reduced delayed neuronal injury within the motor cortex, and improved neurological recovery after SAH. Importantly, therapeutic benefit was strongly time dependent, as delayed CCR2 inhibition after the EBI period failed to improve long-term motor outcomes. To investigate mechanisms underlying monocyte-associated neurotoxicity, human cortical neurons were exposed to hemin-induced hemorrhagic stress in the presence of THP-1 monocytes. Monocyte co-culture exacerbated neuronal injury and increased TNF\u03b1 production, whereas TNF\u03b1 neutralization partially restored neuronal viability under severe hemorrhagic stress conditions. Together, these findings identify early CCR2-dependent monocyte recruitment temporally linked to inflammatory amplification and secondary neuronal injury during the EBI phase following SAH. Our results support early, time-sensitive CCR2 modulation as a potential therapeutic strategy for improving neurological recovery after SAH.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1888359","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:32:29Z","timestamp":1786685549000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Early CCR2-dependent monocyte recruitment defines a critical neuroinflammatory window after subarachnoid hemorrhage"],"prefix":"10.3389","volume":"17","author":[{"given":"Dong Su","family":"Kang","sequence":"first","affiliation":[{"name":"Translational Immunology Lab, Department of Transdisciplinary Medicine, Seoul National University Hospital","place":["Seoul, Republic of Korea"]},{"name":"Immunology Core Facility, Department of Translational Research Center, Biomedical Research Institute, Seoul National University Hospital","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hyeok","family":"Seok","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Macrophage Lab, Department of Microbiology and Immunology, Seoul National University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Institute of Endemic Diseases, Seoul National University Medical Research Center (SNUMRC)","place":["Seoul, Republic of Korea"]},{"name":"Cancer Research Institute, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Hoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Cenyxbiotech Inc.","place":["Seoul, Republic of Korea"]},{"name":"Department of Neurology, Seoul National University Hospital","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Rang","family":"Na","sequence":"additional","affiliation":[{"name":"Translational Immunology Lab, Department of Transdisciplinary Medicine, Seoul National University Hospital","place":["Seoul, Republic of Korea"]},{"name":"Immunology Core Facility, Department of Translational Research Center, Biomedical Research Institute, Seoul National University Hospital","place":["Seoul, Republic of Korea"]},{"name":"Department of Medicine, Seoul National University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-019-00829-x","article-title":"Aneurysmal subarachnoid hemorrhage: An overview of inflammation-induced cellular 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