Vitamin D—A New Perspective in Treatment of Cerebral Vasospasm

Neurosurgery 88 (3) 2021: 674–685

Cerebral vasospasm (CVS) is a frequent complication after subarachnoid hemorrhage (SAH), with no sufficient therapy and a complex pathophysiology.

OBJECTIVE: To explore the vitamin D system as a potential treatment for CVS.

METHODS: 25-vitamin D3 levels tested between 2007 and 2015 and data of SAH patients admitted during themonthswith a peak vs nadir of VitD3 valueswere 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.

RESULTS: 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 inmice. Deletion of the vitaminDreceptor in the endothelium or in myeloid cells decreased the protective 1,25-VitD3 effect. Co-culture experiments ofmyeloid 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.

CONCLUSION: 1,25-VitD3 attenuates CVS after SAH by inducing SDF1α. However, VitD administration should be tested as optional treatment to prevent CVS.