{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:40:38Z","timestamp":1790480438790,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose:<\/jats:title>\n            <jats:p>Spontaneous intracerebral hemorrhage (sICH) is a common form of hemorrhagic stroke, with high mortality and morbidity. Pathophysiological mechanisms in sICH are poorly understood and treatments limited. Neuroinflammation driven by microglial-macrophage activation contributes to brain damage post-sICH. We aim to test the hypothesis that an anti-inflammatory (repair) process occurs in parallel with neuroinflammation in clinical sICH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We performed quantitative analysis of immunohistochemical markers for microglia and macrophages (Iba1, CD68, TMEM119, CD163, and CD206) in brain tissue biospecimens 1 to 12 days post-sICH and matched control cases. In a parallel, prospective group of patients, we assayed circulating inflammatory markers (CRP [C-reactive protein], total white cell, and monocyte count) over 1 to 12 days following sICH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              In 27 supratentorial sICH cases (n=27, median [interquartile range] age: 59 [52\u201380.5], 14F\/13M) all microglia-macrophage markers increased post-sICH, relative to control brains. Anti-inflammatory markers (CD163 and CD206) were elevated alongside proinflammatory markers (CD68 and TMEM119). CD163 increased progressively post-sICH (15.0-fold increase at 7\u201312 days,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). CD206 increased at 3 to 5 days (5.2-fold,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) then returned to control levels at 7 to 12 days. The parenchymal immune response combined brain-derived microglia (TMEM119 positive) and invading monocyte-derived macrophages (CD206 positive). In a prospective sICH patient cohort (n=26, age 74 [66\u201379], National Institutes of Health Stroke Scale on admission: 8 [4\u201317]; 14F\/12M) blood CRP concentration and monocyte density (but not white blood cell) increased post-sICH. CRP increased from 0 to 2 to 3 to 5 days (8.3-fold,\n              <jats:italic>P<\/jats:italic>\n              =0.020) then declined at 7 to 12 days. Monocytes increased from 0 to 2 to 3 to 5 days (1.8-fold,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) then declined at 7 to 12 days.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>An anti-inflammatory pathway, enlisting native microglia and blood monocytes, occurs alongside neuroinflammation post-sICH. This novel pathway offers therapeutic targets and a window of opportunity (3\u20135 days post-sICH) for delivery of therapeutics via invading monocytes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.121.034673","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T09:00:21Z","timestamp":1626771621000},"page":"3613-3623","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Innate Immune Anti-Inflammatory Response in Human Spontaneous Intracerebral Hemorrhage"],"prefix":"10.1161","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7459-8437","authenticated-orcid":true,"given":"Anan","family":"Shtaya","sequence":"first","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute, St George\u2019s University of London, United Kingdom (A.S., L.R.B., A.C.P., A.H.H.)."},{"name":"Wessex Spinal Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom (A.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie R.","family":"Bridges","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute, St George\u2019s University of London, United Kingdom (A.S., L.R.B., A.C.P., A.H.H.)."},{"name":"Department of Cellular Pathology (L.R.B.), St George\u2019s University Hospitals NHS Foundation Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1332-8761","authenticated-orcid":true,"given":"Rebecca","family":"Williams","sequence":"additional","affiliation":[{"name":"Neurology Department (R.W., S.T., L.Z., A.C.P., A.H.H.), St George\u2019s University Hospitals NHS Foundation Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Trippier","sequence":"additional","affiliation":[{"name":"Neurology Department (R.W., S.T., L.Z., A.C.P., A.H.H.), St George\u2019s University Hospitals NHS Foundation Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6983-7915","authenticated-orcid":true,"given":"Liqun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Neurology Department (R.W., S.T., L.Z., A.C.P., A.H.H.), St George\u2019s University Hospitals NHS Foundation Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony C.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute, St George\u2019s University of London, United Kingdom (A.S., L.R.B., A.C.P., A.H.H.)."},{"name":"Neurology Department (R.W., S.T., L.Z., A.C.P., A.H.H.), St George\u2019s University Hospitals NHS Foundation Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.R.","family":"Nicoll","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, United Kingdom (J.A.R.N., D.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5884-130X","authenticated-orcid":true,"given":"Delphine","family":"Boche","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, United Kingdom (J.A.R.N., D.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7877-8013","authenticated-orcid":true,"given":"Atticus H.","family":"Hainsworth","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute, St George\u2019s University of London, United Kingdom (A.S., L.R.B., A.C.P., A.H.H.)."},{"name":"Neurology Department (R.W., S.T., L.Z., A.C.P., 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