{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:07:40Z","timestamp":1780430860246,"version":"3.54.1"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,10,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Many therapies designed to prevent delayed cerebral ischemia (DCI) and improve neurological outcome in aneurysmal subarachnoid hemorrhage (SAH) have failed, likely because of targeting only one element of what has proven to be a multifactorial disease. We previously demonstrated that initiating hypoxic conditioning before SAH (hypoxic preconditioning) provides powerful protection against DCI. Here, we expanded upon these findings to determine whether hypoxic conditioning delivered at clinically relevant time points after SAH (hypoxic postconditioning) provides similarly robust DCI protection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In this study, we found that hypoxic postconditioning (8% O\n              <jats:sub>2<\/jats:sub>\n              for 2\u00a0hours) initiated 3\u00a0hours after SAH provides strong protection against cerebral vasospasm, microvessel thrombi, and neurological deficits. By pharmacologic and genetic inhibition of SIRT1 (sirtuin 1) using EX527 and global\n              <jats:italic>Sirt1<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice, respectively, we demonstrated that this multifaceted DCI protection is SIRT1 mediated. Moreover, genetic overexpression of SIRT1 using\n              <jats:italic>Sirt1\u2010Tg<\/jats:italic>\n              mice, mimicked the DCI protection afforded by hypoxic postconditioning. Finally, we found that post\u2010SAH administration of resveratrol attenuated cerebral vasospasm, microvessel thrombi, and neurological deficits, and did so in a SIRT1\u2010dependent fashion.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The present study indicates that hypoxic postconditioning provides powerful DCI protection when initiated at clinically relevant time points, and that pharmacologic augmentation of SIRT1 activity after SAH can mimic this beneficial effect. We conclude that conditioning\u2010based therapies administered after SAH hold translational promise for patients with SAH and warrant further investigation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.021113","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T09:13:08Z","timestamp":1633684388000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Sirtuin 1 Mediates Protection Against Delayed Cerebral Ischemia in Subarachnoid Hemorrhage in Response to Hypoxic Postconditioning"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3913-8448","authenticated-orcid":false,"given":"Deepti","family":"Diwan","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery Washington University School of Medicine St. Louis MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2056-6610","authenticated-orcid":false,"given":"Ananth K.","family":"Vellimana","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Washington University School of Medicine St. Louis MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane J.","family":"Aum","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Washington University School of Medicine St. Louis MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3709-8892","authenticated-orcid":false,"given":"Julian","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Washington University School of Medicine St. Louis MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Washington University School of Medicine St. Louis MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Washington University School of Medicine St. Louis MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Hee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacology A.T. 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