{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:31:32Z","timestamp":1790721092170,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T00:00:00Z","timestamp":1543449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP15H05719"],"award-info":[{"award-number":["JP15H05719"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004807","name":"DFG","doi-asserted-by":"publisher","award":["DR 323\/5\u20101"],"award-info":[{"award-number":["DR 323\/5\u20101"]}],"id":[{"id":"10.13039\/100004807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["CSB 01 EO 0801"],"award-info":[{"award-number":["CSB 01 EO 0801"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Traditionally, angiographic vasospasm (aVS) has been thought to cause delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, successful treatment of aVS alone does not result in improved neurological outcome. Therefore, there may be other potential causes of poor neurological outcome, including spreading depolarization (SD). A recent study showed beneficial effects of cilostazol on DCI and neurological outcome. The present prospective clinical trial and experimental study focused on effects of cilostazol on SDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifty aSAH patients were treated with clip ligation and randomly assigned to a cilostazol (n\u2009=\u200923) or control group (n\u2009=\u200927). Effects of cilostazol on DCI, aVS, and SDs, measured with subdural electrodes, were examined. The effect of cilostazol on SD\u2010induced perfusion deficits (spreading ischemia) was assessed in an aSAH\u2010mimicking model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was a trend for less DCI in the cilostazol group, but it did not reach our threshold for statistical significance (13.0% vs 40.0%, odds ratio\u2009=\u20090.266, 95% confidence interval [CI]\u2009=\u20090.059\u20131.192, <jats:italic>p<\/jats:italic>\u2009=\u20090.084). However, the total SD\u2010induced depression duration per recording day (22.2 vs 30.2 minutes, \u03b2\u2009=\u2009\u2212251.905, 95% CI\u2009=\u2009\u2212488.458 to \u221215.356, <jats:italic>p<\/jats:italic>\u2009=\u20090.043) and the occurrence of isoelectric SDs (0 vs 4 patients, \u03b2\u2009=\u2009\u22120.916, 95% CI\u2009=\u2009\u22121.746 to \u22120.085, <jats:italic>p<\/jats:italic>\u2009=\u20090.037) were significantly lower in the cilostazol group. In rats, cilostazol significantly shortened SD\u2010induced spreading ischemia compared to vehicle (Student <jats:italic>t<\/jats:italic> test, difference\u2009=\u200930.2, 95% CI\u2009=\u20095.3\u201355.1, <jats:italic>p<\/jats:italic>\u2009=\u20090.020).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Repair of the neurovascular response to SDs by cilostazol, as demonstrated in the aSAH\u2010mimicking model, may be a promising therapy to control DCI. Ann Neurol 2018;84:873\u2013885<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25361","type":"journal-article","created":{"date-parts":[[2018,10,20]],"date-time":"2018-10-20T13:00:26Z","timestamp":1540040426000},"page":"873-885","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Cilostazol decreases duration of spreading depolarization and spreading ischemia after aneurysmal subarachnoid hemorrhage"],"prefix":"10.1002","volume":"84","author":[{"given":"Kazutaka","family":"Sugimoto","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Yamaguchi University School of Medicine  Yamaguchi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadahiro","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Yamaguchi University School of Medicine  Yamaguchi 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