Abstract WP100: Vitamin D Deficiency Induced Alteration in Blood Brain Barrier Following Stroke in Rats

Abstract

Background: Growing evidence suggests that Vitamin D hormone deficiency (VDH def ) is a risk factor for ischemic stroke and its severity. Blood-brain barrier (BBB) impairment is a marker of secondary cerebral injury following stroke and is associated with an increased propensity for hemorrhage. Our in vitro work showed that VDH treatment reduces BBB damage after hypoxia/reperfusion injury via VDR-mediated NF-kB-MMP9 pathways. We explored the role of VDH in maintaining BBB integrity in a rodent model of stroke. Methods: Male Wistar rats (n=48) were assigned to one of two diet cohorts, VDH-sufficient (VDH suf ) and VDH def . The VDH suf group was fed standard chow and the VDH def group was fed a VDH-null version of the same diet for 8 weeks. Animals from both cohorts received either sham or transient middle cerebral artery occlusion (tMCAO) surgeries and were assigned to one of 4 groups (n=12/group): sham VDH suf , MCAO+VDH suf , Sham+VDH def , or MCAO+VDH def . Rats were killed at 72h and one group of animals (n=6) was used for immunohistological assays and other group (n=6) used for western blot assays. Their brains were evaluated for BBB permeability, MMP-9 activity, alteration of TJ proteins and VDR expression. Results: VDH def induced a significant increase in BBB permeability as measured by IgG extravasation in sham VDH def control rats. Following MCAO, expression of MMP-9 and the TJ proteins occludin and claudin-5 increased significantly in the MCAO+VDH def group compared to the MCAO+VDH suf group. IgG extravasation after MCAO was observed to be significantly higher in the MCAO+VDH def than the MCAO+VDH suf group, indicating more severe BBB injury in the VDH def group. Conclusion: Our result showed greater BBB dysfunction in the sham and MCAO groups in the VDH def diet than in the control cohort, indicating more severe BBB injury in rats fed a VDH def diet. This finding that VDH status modulates BBB integrity may help explain the clinical correlations between low serum VDH levels and stroke.