{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:31:27Z","timestamp":1787506287550,"version":"build-2736575974"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>\n                      FKBP5 (FK506-binding protein 51, protein), encoded by the\n                      <jats:italic toggle=\"yes\">FKBP5<\/jats:italic>\n                      (gene, human), is a glucocorticoid receptor-regulating cochaperone. FKBP5 has been suggested as a mediator between stress, vascular morbidity, and neuropsychiatric complications. In this translational proof-of-concept study, we investigated the impact of\n                      <jats:italic toggle=\"yes\">FKBP5<\/jats:italic>\n                      on stroke outcome in mice and men.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Fkbp5<\/jats:italic>\n                      (gene, mouse) knockout and wild-type mice were subjected to transient brain ischemia. Lesion volume was assessed at 48 hours after stroke using magnetic resonance imaging. Circulating corticosterone level and adrenal gland weight were determined at 72 hours. Observational data from the Prospective Cohort with Incident Stroke Berlin were used to explore associations between\n                      <jats:italic toggle=\"yes\">FKBP5<\/jats:italic>\n                      gene variants and functional outcome after 1 year. Poor functional outcome at 1 year was defined as a modified Rankin Scale score of 0 to 1 versus 2 to 6. Risk allele\n                      <jats:italic toggle=\"yes\">ACT<\/jats:italic>\n                      from a predefined\n                      <jats:italic toggle=\"yes\">FKBP5<\/jats:italic>\n                      haplotype (rs9296158, rs3800373, rs1360780) versus non-\n                      <jats:italic toggle=\"yes\">ACT<\/jats:italic>\n                      was used as the exposure variable. Logistic regression analyses were performed and adjusted for potential confounders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Fkbp5<\/jats:italic>\n                      knockout mice showed reduced corticosterone levels and adrenal weights, together with smaller infarct lesions at 48 hours. Four hundred thirty-three patients with available\n                      <jats:italic toggle=\"yes\">FKBP5<\/jats:italic>\n                      haplotype were included in the Berlin stroke cohort.\n                      <jats:italic toggle=\"yes\">FKBP5<\/jats:italic>\n                      risk haplotype\n                      <jats:italic toggle=\"yes\">ACT<\/jats:italic>\n                      , which was present in 204 patients, was associated with poor functional outcome at 1 year (adjusted odds ratio, 1.7 [95% CI, 1.02\u20132.7]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      Loss of\n                      <jats:italic toggle=\"yes\">Fkbp<\/jats:italic>\n                      5 leads to improved outcome in experimental stroke. In addition, the\n                      <jats:italic toggle=\"yes\">FKBP<\/jats:italic>\n                      5 risk haplotype, indicative of increased\n                      <jats:italic toggle=\"yes\">FKBP5<\/jats:italic>\n                      expression, was associated with poor functional outcome following stroke.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.125.052905","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T09:00:41Z","timestamp":1773133241000},"page":"1396-1402","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of FKBP5 on Stroke Outcome in Mice and Men: A Translational Study"],"prefix":"10.1161","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8471-8049","authenticated-orcid":true,"given":"Thomas G.","family":"Liman","sequence":"first","affiliation":[{"name":"Department of Neurology (T.G.L., M.-L.H., R.G., K.G., M.E.), Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin-Universittsmedizin Berlin, corporate member of Freie Universitt Berlin and Humboldt-Universitt zu Berlin, Germany."},{"name":"Department of Experimental Neurology (T.G.L., M.-L.H., R.G., K.G., M.E.), Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin-Universittsmedizin Berlin, corporate member of Freie Universitt Berlin and Humboldt-Universitt zu Berlin, Germany."},{"name":"Department of Neurology, Evangelical Hospital Oldenburg, Carl von Ossietzky-University, Germany (T.G.L.)."},{"name":"German Center for Cardiovascular Research (Deutsches Zentrum f\u00fcr Herz-Kreislauferkrankungen) Herz-Kreislauferkrankungen), Berlin, Germany (M.E., T.G.L.)."},{"name":"German Center for Neurodegenerative Diseases (Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen), Berlin (M.E.,T.G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Louise","family":"Herzog","sequence":"additional","affiliation":[{"name":"Department of Neurology (T.G.L., M.-L.H., R.G., K.G., M.E.), Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin-Universittsmedizin Berlin, corporate member of Freie Universitt Berlin and Humboldt-Universitt zu Berlin, Germany."},{"name":"Department of Experimental Neurology (T.G.L., M.-L.H., R.G., K.G., M.E.), Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin-Universittsmedizin Berlin, corporate member of Freie Universitt Berlin and Humboldt-Universitt zu Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7381-904X","authenticated-orcid":true,"given":"Darina","family":"Czamara","sequence":"additional","affiliation":[{"name":"Department Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany (D.C., E.B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4756-7381","authenticated-orcid":true,"given":"Ria","family":"G\u00f6ttert","sequence":"additional","affiliation":[{"name":"Department of Neurology (T.G.L., M.-L.H., R.G., K.G., M.E.), Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin-Universittsmedizin Berlin, corporate member of Freie Universitt Berlin and Humboldt-Universitt zu Berlin, Germany."},{"name":"Department of Experimental Neurology (T.G.L., M.-L.H., R.G., K.G., M.E.), Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin-Universittsmedizin Berlin, corporate member of Freie Universitt Berlin and Humboldt-Universitt zu Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3788-2268","authenticated-orcid":true,"given":"Mathias V.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Neurobiology of Stress Resilience, Max Planck Institute of Psychiatry, Munich, Germany (M.V.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4254-4358","authenticated-orcid":true,"given":"Golo","family":"Kronenberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Z\u00fcrichrich, Switzerland (G.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7088-6618","authenticated-orcid":true,"given":"Elisabeth B.","family":"Binder","sequence":"additional","affiliation":[{"name":"Department Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany (D.C., E.B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1203-641X","authenticated-orcid":true,"given":"Karen","family":"Gertz","sequence":"additional","affiliation":[{"name":"Department of Neurology (T.G.L., M.-L.H., R.G., K.G., M.E.), Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin-Universittsmedizin Berlin, corporate member of Freie Universitt Berlin and Humboldt-Universitt zu Berlin, Germany."},{"name":"Department of Experimental Neurology (T.G.L., M.-L.H., R.G., K.G., M.E.), Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin-Universittsmedizin Berlin, corporate member of Freie Universitt Berlin and Humboldt-Universitt zu Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6520-3720","authenticated-orcid":true,"given":"Matthias","family":"Endres","sequence":"additional","affiliation":[{"name":"Department of Neurology (T.G.L., M.-L.H., R.G., K.G., M.E.), Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin-Universittsmedizin Berlin, corporate member of Freie Universitt Berlin and Humboldt-Universitt zu Berlin, Germany."},{"name":"Department of Experimental Neurology (T.G.L., M.-L.H., R.G., K.G., M.E.), Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin-Universittsmedizin Berlin, corporate member of Freie Universitt Berlin and Humboldt-Universitt zu Berlin, Germany."},{"name":"German Center for Cardiovascular Research (Deutsches Zentrum f\u00fcr Herz-Kreislauferkrankungen) Herz-Kreislauferkrankungen), Berlin, Germany (M.E., T.G.L.)."},{"name":"German Center for Neurodegenerative Diseases (Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen), Berlin 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