{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:15:00Z","timestamp":1767863700187,"version":"3.49.0"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,7,18]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Recent evidence implicates inflammation as a key driver in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH). Inducible nitric oxide synthase (iNOS) is one of the known major mediators of inflammation. We previously showed that an inhalational anesthetic, isoflurane, provides strong protection against delayed cerebral ischemia after SAH. Our current study aims to define the role of iNOS in isoflurane conditioning\u2010induced protection against delayed cerebral ischemia in a mouse model of SAH.<\/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              The experiments used 10\u2010 to 14\u2010week\u2010old male wild\u2010type (C57BL\/6) and iNOS global knockout mice. Anesthetic conditioning was initiated 1\u2009hour after SAH with isoflurane 2% for 1\u2009hour. Isoflurane\u2010induced changes in iNOS expression were measured. N\u2010(3\u2010(aminomethyl) benzyl) acetamidine, a highly selective iNOS inhibitor, was injected intraperitoneally immediately after SAH and then daily. Vasospasm, microvessel thrombosis, and neurological assessment was performed. Data were analyzed by 1\u2010way ANOVA and 2\u2010way repeated measures ANOVA followed by Student Newman Keuls comparison test. Statistical significance was set at\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05. Isoflurane conditioning downregulated iNOS expression in na\u00efve and SAH mice. N\u2010(3\u2010(aminomethyl) benzyl) acetamidine attenuated large artery vasospasm and microvessel thrombosis and improved neurological deficits in wild\u2010type animals. iNOS knockout mice were significantly resistant to vasospasm, microvessel thrombosis, and neurological deficits induced by SAH. Combining isoflurane with N\u2010(3\u2010(aminomethyl) benzyl) acetamidine did not offer extra protection, nor did treating iNOS knockout mice with isoflurane.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Isoflurane conditioning\u2010induced delayed cerebral ischemia protection appears to be mediated by downregulating iNOS. iNOS is a potential therapeutic target to improve outcomes after SAH.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.029975","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T11:01:03Z","timestamp":1689332463000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Isoflurane Conditioning\u2010Induced Delayed Cerebral Ischemia Protection in Subarachnoid Hemorrhage\u2014Role of Inducible Nitric Oxide Synthase"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7633-3384","authenticated-orcid":false,"given":"Meizi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Washington University St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5227-7023","authenticated-orcid":false,"given":"Keshav","family":"Jayaraman","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Washington University St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron J.","family":"Norris","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Washington University St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Washington University St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James W.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Washington University St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jogender","family":"Mehla","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Washington University St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3913-8448","authenticated-orcid":false,"given":"Deepti","family":"Diwan","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Washington University St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ananth","family":"Vellimana","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Washington University St. Louis MO USA"},{"name":"Department of Radiology Washington University St. Louis MO USA"},{"name":"Department of Neurology Washington University St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yousef","family":"Abu\u2010Amer","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Washington University St. Louis MO USA"},{"name":"Department of Cell Biology &amp; Physiology Washington University St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory J.","family":"Zipfel","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Washington University St. Louis MO USA"},{"name":"Department of Neurology Washington University St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9086-0607","authenticated-orcid":false,"given":"Umeshkumar","family":"Athiraman","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Washington University St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.68.3.337"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-013-0316-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.017477"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2020.147169"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22084291"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9070820"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126550"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3171\/2019.3.JNS183512"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyaa356"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.121.035075"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17040497"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2006.04.010"},{"key":"e_1_3_2_14_2","first-page":"1","article-title":"The role of constitutive and inducible nitric oxide synthase in the human brain after subarachnoid hemorrhage","volume":"51","author":"Berra LV","year":"2007","unstructured":"Berra LV, Carcereri De Prati A, Suzuki H, Pasqualin A. 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