{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:28:09Z","timestamp":1793147289762,"version":"4.5.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100005831","name":"foundation for anesthesia education and research","doi-asserted-by":"publisher","award":["MRTG-CT-02-15-2018-Martini"],"award-info":[{"award-number":["MRTG-CT-02-15-2018-Martini"]}],"id":[{"id":"10.13039\/100005831","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"glaxosmithkline","doi-asserted-by":"publisher","award":["No number"],"award-info":[{"award-number":["No number"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurocrit Care"],"published-print":{"date-parts":[[2022,6]]},"DOI":"10.1007\/s12028-021-01398-8","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T18:02:41Z","timestamp":1638813761000},"page":"905-915","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["A Double-Blind, Randomized, Placebo-Controlled Trial of Soluble Epoxide Hydrolase Inhibition in Patients with Aneurysmal Subarachnoid Hemorrhage"],"prefix":"10.1007","volume":"36","author":[{"given":"Ross P","family":"Martini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Siler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Cetas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil J.","family":"Alkayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyse","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4639-3682","authenticated-orcid":false,"given":"Miriam M","family":"Treggiari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"issue":"1","key":"1398_CR1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1093\/bja\/aew095","volume":"117","author":"M Veldeman","year":"2016","unstructured":"Veldeman M, H\u00f6llig A, Clusmann H, Stevanovic A, Rossaint R, Coburn M. Delayed cerebral ischaemia prevention and treatment after aneurysmal subarachnoid haemorrhage: a systematic review. Br J Anaesth. 2016;117(1):17\u201340. https:\/\/doi.org\/10.1093\/bja\/aew095.","journal-title":"Br J Anaesth."},{"key":"1398_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-319-04981-6_1","volume":"120","author":"MR Loch","year":"2015","unstructured":"Loch MR. Vasospasm: my first 25 years-what worked? what didn\u2019t? what next? Acta Neurochir Suppl. 2015;120:1\u201310. https:\/\/doi.org\/10.1007\/978-3-319-04981-6_1.","journal-title":"Acta Neurochir Suppl"},{"key":"1398_CR3","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.pharmthera.2017.05.004","volume":"179","author":"CM Davis","year":"2017","unstructured":"Davis CM, Liu X, Alkayed NJ. Cytochrome P450 eicosanoids in cerebrovascular function and disease. Pharmacol Ther. 2017;179:31\u201346. https:\/\/doi.org\/10.1016\/j.pharmthera.2017.05.004.","journal-title":"Pharmacol Ther."},{"key":"1398_CR4","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.pneurobio.2018.11.001","volume":"172","author":"S Zarriello","year":"2019","unstructured":"Zarriello S, Tuazon JP, Corey S, et al. Humble beginnings with big goals: small molecule soluble epoxide hydrolase inhibitors for treating CNS disorders. Prog Neurobiol. 2019;172:23\u201339. https:\/\/doi.org\/10.1016\/j.pneurobio.2018.11.001.","journal-title":"Prog Neurobiol."},{"key":"1398_CR5","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.prostaglandins.2016.09.002","volume":"132","author":"X Liu","year":"2017","unstructured":"Liu X, Qian ZY, Xie F, et al. Functional screening for G protein-coupled receptor targets of 14,15-epoxyeicosatrienoic acid. Prostaglandins Other Lipid Mediat. 2017;132:31\u201340. https:\/\/doi.org\/10.1016\/j.prostaglandins.2016.09.002.","journal-title":"Prostaglandins Other Lipid Mediat."},{"issue":"5","key":"1398_CR6","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1161\/01.str.27.5.971","volume":"27","author":"NJ Alkayed","year":"1996","unstructured":"Alkayed NJ, Narayanan J, Gebremedhin D, Medhora M, Roman RJ, Harder DR. Molecular characterization of an arachidonic acid epoxygenase in rat brain astrocytes. Stroke. 1996;27(5):971\u20139. https:\/\/doi.org\/10.1161\/01.str.27.5.971.","journal-title":"Stroke."},{"issue":"3\u20134","key":"1398_CR7","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.prostaglandins.2009.06.004","volume":"91","author":"JJ Iliff","year":"2010","unstructured":"Iliff JJ, Jia J, Nelson J, Goyagi T, Klaus J, Alkayed NJ. Epoxyeicosanoid signaling in CNS function and disease. Prostaglandins Other Lipid Mediat. 2010;91(3\u20134):68\u201384. https:\/\/doi.org\/10.1016\/j.prostaglandins.2009.06.004.","journal-title":"Prostaglandins Other Lipid Mediat."},{"issue":"7","key":"1398_CR8","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.1161\/STROKEAHA.114.008560","volume":"46","author":"DA Siler","year":"2015","unstructured":"Siler DA, Berlow YA, Kukino A, et al. Soluble epoxide hydrolase in hydrocephalus, cerebral edema, and vascular inflammation after subarachnoid hemorrhage. Stroke. 2015;46(7):1916\u201322. https:\/\/doi.org\/10.1161\/STROKEAHA.114.008560.","journal-title":"Stroke."},{"issue":"12","key":"1398_CR9","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1038\/sj.jcbfm.9600494","volume":"27","author":"W Zhang","year":"2007","unstructured":"Zhang W, Koerner IP, Noppens R, et al. Soluble epoxide hydrolase: a novel therapeutic target in stroke. J Cereb Blood Flow Metab. 2007;27(12):1931\u201340. https:\/\/doi.org\/10.1038\/sj.jcbfm.9600494.","journal-title":"J Cereb Blood Flow Metab."},{"issue":"7","key":"1398_CR10","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.1161\/strokeaha.107.508325","volume":"39","author":"W Zhang","year":"2008","unstructured":"Zhang W, Otsuka T, Sugo N, et al. Soluble epoxide hydrolase gene deletion is protective against experimental cerebral ischemia. Stroke. 2008;39(7):2073\u20138. https:\/\/doi.org\/10.1161\/strokeaha.107.508325.","journal-title":"Stroke."},{"issue":"6","key":"1398_CR11","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.3171\/2014.7.JNS131990","volume":"121","author":"RP Martini","year":"2014","unstructured":"Martini RP, Ward J, Siler DA, et al. Genetic variation in soluble epoxide hydrolase: association with outcome after aneurysmal subarachnoid hemorrhage. J Neurosurg. 2014;121(6):1359\u201366. https:\/\/doi.org\/10.3171\/2014.7.JNS131990.","journal-title":"J Neurosurg."},{"issue":"2","key":"1398_CR12","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/jcbfm.2014.195","volume":"35","author":"MK Donnelly","year":"2015","unstructured":"Donnelly MK, Conley YP, Crago EA, et al. Genetic markers in the EET metabolic pathway are associated with outcomes in patients with aneurysmal subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2015;35(2):267\u201376. https:\/\/doi.org\/10.1038\/jcbfm.2014.195.","journal-title":"J Cereb Blood Flow Metab."},{"issue":"5","key":"1398_CR13","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1111\/bcp.12855","volume":"81","author":"AL Lazaar","year":"2016","unstructured":"Lazaar AL, Yang L, Boardley RL, et al. Pharmacokinetics, pharmacodynamics and adverse event profile of GSK2256294, a novel soluble epoxide hydrolase inhibitor. Br J Clin Pharmacol. 2016;81(5):971\u20139. https:\/\/doi.org\/10.1111\/bcp.12855.","journal-title":"Br J Clin Pharmacol."},{"issue":"3","key":"1398_CR14","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.chest.2016.10.058","volume":"151","author":"L Yang","year":"2017","unstructured":"Yang L, Cheriyan J, Gutterman DD, et al. Mechanisms of vascular dysfunction in COPD and effects of a novel soluble epoxide hydrolase inhibitor in smokers. Chest. 2017;151(3):555\u201363. https:\/\/doi.org\/10.1016\/j.chest.2016.10.058.","journal-title":"Chest."},{"issue":"4 Pt 2","key":"1398_CR15","doi-asserted-by":"publisher","first-page":"H1171","DOI":"10.1152\/ajpheart.1990.259.4.H1171","volume":"259","author":"EF Ellis","year":"1990","unstructured":"Ellis EF, Police RJ, Yancey L, McKinney JS, Amruthesh SC. Dilation of cerebral arterioles by cytochrome P-450 metabolites of arachidonic acid. Am J Physiol. 1990;259(4 Pt 2):H1171-7. https:\/\/doi.org\/10.1152\/ajpheart.1990.259.4.H1171.","journal-title":"Am J Physiol."},{"issue":"6","key":"1398_CR16","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1093\/aje\/kwq433","volume":"173","author":"H Quan","year":"2011","unstructured":"Quan H, Li B, Couris CM, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173(6):676\u201382. https:\/\/doi.org\/10.1093\/aje\/kwq433.","journal-title":"Am J Epidemiol."},{"issue":"10","key":"1398_CR17","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1161\/strokeaha.110.589275","volume":"41","author":"MD Vergouwen","year":"2010","unstructured":"Vergouwen MD, Vermeulen M, van Gijn J, et al. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010;41(10):2391\u20135. https:\/\/doi.org\/10.1161\/strokeaha.110.589275.","journal-title":"Stroke."},{"issue":"11","key":"1398_CR18","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1161\/01.str.22.11.1389","volume":"22","author":"ML Heizer","year":"1991","unstructured":"Heizer ML, McKinney JS, Ellis EF. 14,15-Epoxyeicosatrienoic acid inhibits platelet aggregation in mouse cerebral arterioles. Stroke. 1991;22(11):1389\u201393. https:\/\/doi.org\/10.1161\/01.str.22.11.1389.","journal-title":"Stroke."},{"issue":"4 Pt 2","key":"1398_CR19","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1161\/01.hyp.25.4.854","volume":"25","author":"Y Zhu","year":"1995","unstructured":"Zhu Y, Schieber EB, McGiff JC, Balazy M. Identification of arachidonate P-450 metabolites in human platelet phospholipids. Hypertension. 1995;25(4 Pt 2):854\u20139. https:\/\/doi.org\/10.1161\/01.hyp.25.4.854.","journal-title":"Hypertension"},{"issue":"12","key":"1398_CR20","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.2174\/1570159x18666200106154203","volume":"18","author":"Y Li","year":"2020","unstructured":"Li Y, Wu P, Bihl JC, Shi H. Underlying mechanisms and potential therapeutic molecular targets in blood-brain barrier disruption after subarachnoid hemorrhage. Curr Neuropharmacol. 2020;18(12):1168\u201379. https:\/\/doi.org\/10.2174\/1570159x18666200106154203.","journal-title":"Curr Neuropharmacol."},{"issue":"2","key":"1398_CR21","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/s12028-019-00710-x","volume":"31","author":"JR Geraghty","year":"2019","unstructured":"Geraghty JR, Davis JL, Testai FD. Neuroinflammation and microvascular dysfunction after experimental subarachnoid hemorrhage: emerging components of early brain injury related to outcome. Neurocrit Care. 2019;31(2):373\u201389. https:\/\/doi.org\/10.1007\/s12028-019-00710-x.","journal-title":"Neurocrit Care."},{"issue":"Pt 1","key":"1398_CR22","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/978-3-7091-0353-1_35","volume":"110","author":"W Ni","year":"2011","unstructured":"Ni W, Gu YX, Song DL, Leng B, Li PL, Mao Y. The relationship between IL-6 in CSF and occurrence of vasospasm after subarachnoid hemorrhage. Acta Neurochir Suppl. 2011;110(Pt 1):203\u20138. https:\/\/doi.org\/10.1007\/978-3-7091-0353-1_35.","journal-title":"Acta Neurochir Suppl."},{"key":"1398_CR23","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.wneu.2016.11.131","volume":"99","author":"M Lenski","year":"2017","unstructured":"Lenski M, Huge V, Briegel J, Tonn JC, Schichor C, Thon N. Interleukin 6 in the cerebrospinal fluid as a biomarker for onset of vasospasm and ventriculitis after severe subarachnoid hemorrhage. World Neurosurg. 2017;99:132\u20139. https:\/\/doi.org\/10.1016\/j.wneu.2016.11.131.","journal-title":"World Neurosurg."},{"key":"1398_CR24","doi-asserted-by":"publisher","first-page":"379","DOI":"10.3389\/fneur.2017.00379","volume":"8","author":"FA Zeiler","year":"2017","unstructured":"Zeiler FA, Thelin EP, Czosnyka M, Hutchinson PJ, Menon DK, Helmy A. Cerebrospinal fluid and microdialysis cytokines in aneurysmal subarachnoid hemorrhage: a scoping systematic review. Front Neurol. 2017;8:379. https:\/\/doi.org\/10.3389\/fneur.2017.00379.","journal-title":"Front Neurol."},{"issue":"52","key":"1398_CR25","doi-asserted-by":"publisher","first-page":"35826","DOI":"10.1074\/jbc.M114.588087","volume":"289","author":"N Matsumoto","year":"2014","unstructured":"Matsumoto N, Suzuki E, Ishikawa M, Shirafuji T, Hasumi K. Soluble epoxide hydrolase as an anti-inflammatory target of the thrombolytic stroke drug SMTP-7. J Biol Chem. 2014;289(52):35826\u201338. https:\/\/doi.org\/10.1074\/jbc.M114.588087.","journal-title":"J Biol Chem."},{"issue":"16","key":"1398_CR26","doi-asserted-by":"publisher","first-page":"3084","DOI":"10.1002\/sim.3182","volume":"27","author":"P Huang","year":"2008","unstructured":"Huang P, Woolson RF, O\u2019Brien PC. A rank-based sample size method for multiple outcomes in clinical trials. Stat Med. 2008;27(16):3084\u2013104.","journal-title":"Stat Med."}],"container-title":["Neurocritical Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12028-021-01398-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12028-021-01398-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12028-021-01398-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T19:29:56Z","timestamp":1652729396000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12028-021-01398-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,6]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["1398"],"URL":"https:\/\/doi.org\/10.1007\/s12028-021-01398-8","relation":{},"ISSN":["1541-6933","1556-0961"],"issn-type":[{"value":"1541-6933","type":"print"},{"value":"1556-0961","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,6]]},"assertion":[{"value":"7 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval\/informed consent"}}]}}