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Secondary cerebral oedema, driven by neuroinflammation and blood\u2013brain barrier (BBB) disruption, critically determines poor outcomes, yet effective targeted therapies remain absent. This study aimed to identify immune cell subsets associated with post\u2010TBI cerebral oedema and to explore their functional contributions in preclinical models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We integrated single\u2010cell transcriptomic datasets from a mouse TBI model (GSE175430) and human intracerebral haemorrhage (ICH) perihaematomal oedema samples (GSE266873) with our previously published temporal bulk RNA\u2010seq profiling data. Through cross\u2010species comparative analysis, Mfuzz clustering, AUCell scoring and gene set enrichment analysis (GSEA),\n                      <jats:italic>Acp5<\/jats:italic>\n                      was identified as an oedema\u2010associated signature gene, and its macrophage\u2010enriched expression pattern was supported by single\u2010cell profiling and immunofluorescence colocalisation. Using the controlled cortical impact (CCI) model, we validated\n                      <jats:italic>Acp5<\/jats:italic>\n                      expression dynamics across injury severities. Pharmacological inhibition (AubipyOMe) and genetic knockout of\n                      <jats:italic>Acp5<\/jats:italic>\n                      were employed to assess brain oedema, neuroinflammation, neurological function and long\u2010term cognitive recovery.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A previously unrecognised population of ACP5\u2010positive monocytes\/macrophages infiltrated the brain parenchyma within 1\u20133\u00a0days post\u2010injury, coinciding with peak oedema severity and neurological deficits. Inhibiting ACP5 significantly reduced brain water content, BBB leakage and proinflammatory cytokines, while improving sensorimotor function. Mechanistically, ACP5\u2010positive macrophages were associated with CSF2\u2010related JAK\/STAT and NF\u2010\u03baB signalling. Genetic\n                      <jats:italic>Acp5<\/jats:italic>\n                      ablation attenuated acute macrophage infiltration and neuroinflammation, and was associated with improved long\u2010term behavioural outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ACP5\u2010positive macrophages represent an injury\u2010associated myeloid population that contributes to neuroinflammatory and oedema\u2010related phenotypes after experimental TBI. Pharmacological and genetic findings provide preclinical evidence supporting further investigation of ACP5 and CSF2\u2010related signalling in secondary TBI injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70845","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:29:51Z","timestamp":1790321391000},"source":"Crossref","is-referenced-by-count":0,"title":["ACP5\u2010positive macrophages contribute to cerebral oedema and neuroinflammation after traumatic brain injury"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6243-3854","authenticated-orcid":false,"given":"Dang","family":"Hanhan","sequence":"first","affiliation":[{"name":"China\u2013Japan Friendship Hospital (Institute of Clinical Medical Sciences) Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"},{"name":"Department of Neurosurgery China\u2013Japan Friendship Hospital  Beijing 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