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Neurosurgical removal of intracerebral hematoma has limited benefit and no pharmacotherapies are available. In acute ICH, primary tissue damage is followed by secondary pathology, where the cellular and neuroinflammatory changes are poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied histological changes in<jats:italic>postmortem<\/jats:italic>tissue from a cohort of spontaneous supra\u2010tentorial primary ICH cases (<jats:italic>n<\/jats:italic>\u00a0=\u00a027) with survival of 1\u201312\u00a0days, compared to a matched control group (<jats:italic>n<\/jats:italic>\u00a0=\u00a016) examined in corresponding regions. Hematoxylin\u2013eosin and microglial (Iba1) immunolabelled sections were assessed at 0\u20132, 3\u20135, and 7\u201312\u00a0days post\u2010ICH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Peri\u2010hematoma, the observed ICH\u2010related changes include edema, tissue neutrophils and macrophages from day 1. Ischemic neurons and swollen endothelial cells were common at day 1 and universal after day 5, as were intramural erythrocytes within small vessel walls. Activated microglia were evident at day 1 post\u2010ICH. There was a significant increase in Iba1 positive area fraction at 0\u20132 (threefold), 3\u20135 (fourfold), and 7\u201312\u00a0days post ICH (ninefold) relative to controls. Giant microglia were detected peri\u2010hematoma from day 5 and consistently 7\u201312\u00a0days post\u2010ICH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our data indicate that neuroinflammatory processes commence from day 1 post\u2010ICH with changing microglial size and morphology following ICH and up to day 12. From day 5 some microglia exhibit a novel multiply nucleated morphology, which may be related to changing phagocytic function. Understanding the time course of neuroinflammatory changes, post\u2010ICH may reveal novel targets for therapy and brain restoration.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50842","type":"journal-article","created":{"date-parts":[[2019,7,13]],"date-time":"2019-07-13T08:48:03Z","timestamp":1563007683000},"page":"1465-1479","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Rapid neuroinflammatory changes in human acute intracerebral hemorrhage"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7459-8437","authenticated-orcid":false,"given":"Anan","family":"Shtaya","sequence":"first","affiliation":[{"name":"Neuroscience Research Centre, Molecular and Clinical Sciences Research Institute St. George\u2019s, University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie R.","family":"Bridges","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology St George's University Hospitals NHS Foundation Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M.","family":"Esiri","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences Oxford University Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Lam\u2010Wong","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology St George's University Hospitals NHS Foundation Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A. 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