{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:10:54Z","timestamp":1791875454061,"version":"4.3.4"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/ mailto:journals.permissions@oup.com"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurosurg.","NEUROS"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Cerebral vasospasm (CVS) is a frequent complication after subarachnoid hemorrhage (SAH), with no sufficient therapy and a complex pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>To explore the vitamin D system as a potential treatment for CVS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>25-vitamin D3 levels tested between 2007 and 2015 and data of SAH patients admitted during the months with a peak vs nadir of VitD3 values were analyzed, retrospectively. We prospectively correlated VitD3 and vasospasm\/outcome data in SAH patients admitted in 2017. An experimental mice SAH model and cell culture model were used to investigate the effect of 1,25-dihydroxyvitamin D3 (1,25-VitD3). Additionally, the mediators acting in the VitD mechanism were researched and detected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Based on the retrospective analysis demonstrating an increased frequency of vasospasm in SAH patients during the low vitamin D period in winter, we started basic research experiments. Active 1,25-VitD3 hormone attenuated CVS, neurological deficit, and inflammation after intrathecal blood injection in mice. Deletion of the vitamin D receptor in the endothelium or in myeloid cells decreased the protective 1,25-VitD3 effect. Co-culture experiments of myeloid and endothelial cells with blood confirmed the anti-inflammatory 1,25-VitD3 effect but also revealed an induction of stroma-cell-derived factor 1\u03b1 (SDF1\u03b1), vascular endothelial growth factor, and endothelial nitric oxide synthase by 1,25-VitD3. In mice, SDF1\u03b1 mimicked the protective effect of 1,25-VitD3 against CVS. From bench to bedside, CVS severity was inversely correlated with vitamin D plasma level, prospectively. Patients with more severe CVS exhibited attenuated expression of SDF1\u03b1 and 1,25-VitD3-responsive genes on circulating myeloid cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>1,25-VitD3 attenuates CVS after SAH by inducing SDF1\u03b1. However, VitD administration should be tested as optional treatment to prevent CVS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuros\/nyaa484","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T08:28:45Z","timestamp":1602577725000},"page":"674-685","source":"Crossref","is-referenced-by-count":15,"title":["Vitamin D\u2014A New Perspective in Treatment of Cerebral Vasospasm"],"prefix":"10.1227","volume":"88","author":[{"given":"Sepide","family":"Kashefiolasl","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University Hospital Frankfurt, Frankfurt, Germany"},{"name":"Institute for Cardiovascular Physiology, Goethe-University, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias S","family":"Leisegang","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Physiology, Goethe-University, Frankfurt, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Rhein-Main, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeska","family":"Helfinger","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Physiology, Goethe-University, Frankfurt, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Rhein-Main, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1530-1378","authenticated-orcid":false,"given":"Christoph","family":"Sch\u00fcrmann","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Physiology, Goethe-University, Frankfurt, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Rhein-Main, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Pfl\u00fcger-M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Physiology, Goethe-University, Frankfurt, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Rhein-Main, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Voahanginirina","family":"Randriamboavonjy","sequence":"additional","affiliation":[{"name":"German Center of Cardiovascular Research (DZHK), Rhein-Main, Frankfurt, Germany"},{"name":"Institute for Vascular Signalling, Goethe-University, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea E","family":"Vasconez","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Physiology, Goethe-University, Frankfurt, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Rhein-Main, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Carmeliet","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Badenhoop","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Internal Medicine 1, University Hospital Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"Hintereder","sequence":"additional","affiliation":[{"name":"Central Laboratory, University Hospital Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Seifert","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Hospital Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Physiology, Goethe-University, Frankfurt, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Rhein-Main, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Konczalla","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Hospital Frankfurt, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf P","family":"Brandes","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Physiology, Goethe-University, Frankfurt, Germany"},{"name":"German Center of Cardiovascular Research (DZHK), Rhein-Main, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,3]]},"reference":[{"issue":"6","key":"bib1-20231011","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1161\/STR.0b013e3182587839","article-title":"Guidelines for the management of aneurysmal subarachnoid hemorrhage. 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