Vitamin D-A New Perspective in Treatment of Cerebral Vasospasm.

Cerebral vasospasm (CVS) is a frequent complication after subarachnoid hemorrhage (SAH), with no sufficient therapy and a complex pathophysiology. To explore the vitamin D system as a potential treatment for CVS. 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. 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 1α (SDF1α), vascular endothelial growth factor, and endothelial nitric oxide synthase by 1,25-VitD3. In mice, SDF1α 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 SDF1α and 1,25-VitD3-responsive genes on circulating myeloid cells. 1,25-VitD3 attenuates CVS after SAH by inducing SDF1α. However, VitD administration should be tested as optional treatment to prevent CVS. © Congress of Neurological Surgeons 2020.

Citation

Sepide Kashefiolasl, Matthias S Leisegang, Valeska Helfinger, Christoph Schürmann, Beatrice Pflüger-Müller, Voahanginirina Randriamboavonjy, Andrea E Vasconez, Geert Carmeliet, Klaus Badenhoop, Gudrun Hintereder, Volker Seifert, Katrin Schröder, Juergen Konczalla, Ralf P Brandes. Vitamin D-A New Perspective in Treatment of Cerebral Vasospasm. Neurosurgery. 2021 Feb 16;88(3):674-685

Mesh Tags

Substances

PMID: 33269399

search → result