{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T06:18:20Z","timestamp":1787811500037,"version":"build-2784847793"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Early brain injury (EBI) following subarachnoid hemorrhage (SAH) critically determines neurological outcomes, yet the cellular drivers remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To systematically dissect acute pathogenic programs, we performed single-cell RNAsequencing of CD45\n                      <jats:sup>+<\/jats:sup>\n                      immune cells isolated from a mouse model of SAH, coupled with weighted gene co-expression network analysis (WGCNA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      This revealed a 24-h-specific injury module enriched for inflammatory and myeloid-related pathways. Mapping this module onto the single-cell landscape identified neutrophils as the principal cellular mediators. High-resolution subclustering further defined a distinct neutrophil subset, N_04, as the primary carrier of the 24-h pathogenic signature. N_04 is transcriptionally primed for Neutrophil Extracellular Trap (NET) formation, with key effectors including Padi4, Mmp8, and Lcn2, and spatial mapping localized N_04 to regions adjacent to the puncture site. Transcriptional regulatory analysis identified Padi4, Nfe2, and Cebpe as central nodes sustaining N_04 effector identity, while\n                      <jats:italic>in vivo<\/jats:italic>\n                      Padi4 deficiency or NET degradation markedly alleviated neurological deficits. Pseudotime and computational perturbation analyses indicated that N_04 represents a terminal effector state orchestrating hyper-inflammatory, degranulation, and stress-response programs. Intercellular communication modeling further positioned N_04 as a signaling hub, mediating bidirectional crosstalk with macrophages via Cxcl, Ccl, and APP pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, these findings define a NET-competent neutrophil subpopulation as a central driver of acute post-SAH brain injury and nominate Padi4-dependent NETosis as a potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1923057","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:34:37Z","timestamp":1787808877000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A NET-competent neutrophil subpopulation drives early brain injury after subarachnoid hemorrhage"],"prefix":"10.3389","volume":"20","author":[{"given":"Kaikai","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]},{"name":"Zhejiang Key Laboratory of Research and Transformation for Major Neurological Diseases","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]},{"name":"Zhejiang Key Laboratory of Research and Transformation for Major Neurological Diseases","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Traditional Chinese Medicine Hospital of Linping District","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Huang","sequence":"additional","affiliation":[{"name":"Ningbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangmin","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Traditional Chinese Medicine Hospital of Linping District","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchun","family":"Liu","sequence":"additional","affiliation":[{"name":"Ningbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/s12974-019-1578-1","article-title":"Inflammation in delayed ischemia and functional outcomes after subarachnoid hemorrhage.","volume":"16","author":"Ahn","year":"2019","journal-title":"J. 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