1261. Vitamin D – A New Perspective in Treatment of Cerebral Vasospasm after Subarachnoid Hemorrhage

Authors: Sepide Kashefiolasl; Matthias Leisegang, PhD; Valeska Helfinger, PhD; Christoph Schürmann, PhD; Voahanginirina Randriamboavonjy, PhD; Geert Carmeliet, MD, PhD; Klaus Badenhoop, MD, PhD; Katrin Schröder, PhD; Volker Seifert, MD, PhD; Ralf Brandes, MD, PhD; Juergen Konczalla, MD, PhD (Frankfurt am Main, Germany)


Cerebral vasospasm (CVS) is a severe complication after subarachnoid hemorrhage (SAH). We explored vitamin D (VitD) as a possible therapeutic option for CVS in SAH patients.


The translational study was composed of an experimental and a clinical arm. 25-VitaminD3 (VitD3) levels tested between 2007-2015 and data of SAH patients admitted during the months with a peak versus nadir of VitD3-values were analyzed, retrospectively. Furthermore, we prospectively correlated VitD3 and vasospasm/outcome data in SAH patients admitted in 2017 after written informed consent. An experimental mice SAH model and cell culture model using 1,25-dihydroxy-VitaminD3 (1,25-VitD3) or not were used to investigate the pathophysiological differences. Additionally, the mediators acting in the VitD mechanism were researched and detected.


In SAH patients an increased frequency of severe vasospasm during the low VitD period was observed (p<0,05, OR1,7). Active 1,25-VitD3 attenuated CVS development in mice, as determined by vessel diameter of basilar artery (BA) and reduced neurological deficit. An attenuated inflammation of the BA was detected under 1,25-VitD3-treatment, additionally. Deletion of the myeloid or endothelial VitD-receptor decreased the protective 1,25-VitD3-effect. Co-culture experiments of myeloid and endothelial cells with blood confirmed the anti-inflammatory effect of 1,25-VitD3 but also revealed a selective induction of SDF1α, VEGF and eNOS. In mice, SDF1α mimicked the protective effect of 1,25-VitD3. Also, in the prospective study of 23 patients high VitD3 levels were associated with a significant higher chance for favorable outcome (p<0,05, OR18). CVS severity was inversely correlated with the VitD level (r=-0,63, p<0.001). Patients with severe CVS exhibited attenuated expression of SDF1α and VitD-responsive genes on circulating myeloid cells.


Patients with VitD-deficiency have a higher rate of severe CVS and worse outcome. 1,25-VitD3, by inducing SDF1α, attenuates CVS after subarachnoid hemorrhage. VitD administration should be tested as a treatment option to prevent CVS in SAH patients.