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)

Introduction:

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.

Methods:

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.

Results:

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.

Conclusion:

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.