Abstract WP118: Roles of Vitamin D Deficiency in the Development of Intracranial Aneurysm Rupture

Introduction: Beyond its essential roles in bone and mineral homeostasis, vitamin D has been implicated in a wide range of chronic pathology. Clinical studies have shown the increased incidence of subarachnoid hemorrhage during winter to spring months when vitamins D levels are decreased because of the less sunlight exposure. Therefore, we hypothesized that vitamin D contributes to the rupture of intracranial aneurysm. Using a mouse model of intracranial aneurysm, we examined whether vitamin D deficiency promotes intracranial aneurysm rupture. Methods and Materials: We used 15-week old C57BL/6 male and female mice. To induce aneurysm, we combined induced systemic hypertension (deoxycorticosterone acetate-salt hypertension) and a single injection of elastase (17.5 mU) into the cerebrospinal fluid at the right basal cistern. Mice were assigned to either (1) control (vitamin D 2000 IU/kg) or (2) vitamin D deficient diet (VDD) (vitamin D 0 IU/kg) group. The diet treatment was started seven weeks prior to aneurysm induction and continued until 21 days after aneurysm induction. In female mice, bilateral ovariectomy was also performed one week before aneurysm induction to avoid estrogen-dependent changes in vitamin D levels. Results: In male mice, the vitamin D deficient diet significantly increased aneurysmal rupture compared to the control diet (control vs. VDD: 54% vs. 93%; P < 0.01). In ovariectomized female mice, there was no significant difference in the rupture rate between two diet treatment groups (control vs. VDD: 88% vs. 86%; P = 1.0). There was no significant difference in the incidence of aneurysmal formation between two groups in both sexes. Experiments using sham-ovariectomized female mice are currently ongoing. Conclusion: Our preliminary data suggest that vitamin D deficiency promotes intracranial aneurysmal rupture in male mice, but not in ovariectomized female mice. There may be sex-dependent or sex steroids dependent effects of vitamin D on the development of intracranial aneurysm rupture. Our ongoing experiments will elucidate the underlying mechanisms for the potential sex differences in the contributions of vitamin D to the pathophysiology of intracranial aneurysm.