Vitamin D Receptor Deficiency Impairs Pial Collateral Circulation in Mice

Abstract

Vitamin D deficiency is a global health problem, which can increase the risk of cerebrovascular diseases including ischaemic stroke. However, the pathophysiological mechanism underlying this association is not well understood yet. The goal of the present work was to examine the impacts of vitamin D deficiency on the mouse pial collateral circulation which might provide a compensatory pathway after unilateral common carotid artery occlusion (CAO). The morphology of the leptomeningeal collaterals and the distance of the anastomotic line (half distance between the nearest branching points of the anterior cerebral artery (ACA) and the middle cerebral artery (MCA)) from the midline were evaluated after staining of the cerebral vasculature in adult male mice carrying a functionally inactive vitamin D receptor (KO, n=6) and in their wild‐type littermates (WT, n=6). The acute cerebrocortical blood flow (CoBF) changes after CAO was measured in anesthetized WT (n=8) and KO (n=8) mice using laser speckle imaging to evaluate regional differences in the territories supplied by the ACA and MCA, i.e. the frontoparietal and temporal cortices, respectively. Vitamin D deficiency decreased the number of leptomeningeal collaterals between the ACA and MCA, whereas the tortuosity of the collaterals was enhanced. The anastomotic line measured at 4 mm caudally from the frontal pole was located cc. 400 μm closer to the midline in KO than in WT mice, therefore the territory supplied by the ACA decreased. The maximal CoBF reductions were similar between the two groups in the temporal cortex, whereas in the frontoparietal cortex more severe hypoperfusion was developed in the KO animals, as the blood flow in the ipsilateral frontoparietal region showed a decrease of 13% compared to the contralateral region, whereas this difference was only 6% in WT mice. In conclusion, vitamin D deficiency leads to impaired development of leptomeningeal collaterals, as well as enhanced CoBF reduction in the frontoparietal cortex after CAO. These morphological and functional alterations can potentially compromise the cerebral circulation, therefore it may increase the risk of cerebrovascular diseases and worsen the outcome of stroke.Support or Funding InformationEFOP‐3.6.3‐VEKOP‐16‐2017‐00009, OTKA K‐112964, OTKA K‐125174, NVKP‐16‐1‐2016‐0042