PhD Scientific Days 2021

TT_III_L: Theoretical and Translational Medicine III. Lectures

Vitamin D Receptor Deficiency Impairs the Adaptation of the Cerebrocortical Microcirculation to Unilateral Carotid Artery Occlusion

Text of the abstract

Introduction
Vitamin D deficiency is a global health problem, which is associated with the increased risk of cerebrovascular diseases including ischemic stroke. However, the pathophysiological mechanisms are still obscure.
Aims
Our goal was to analyze the impact of vitamin D receptor (VDR) signaling on the anatomical and functional aspects of cerebrovascular adaptation to unilateral carotid artery occlusion (CAO), a common consequence of atherosclerosis and cause of ischemic stroke.
Methods
The cerebrocortical blood flow changes after CAO were measured in anesthetized, adult male mice carrying a functionally inactive vitamin D receptor (VDRΔ/Δ) and in their wild-type littermates using laser speckle imaging. The compensatory blood flow increase in the contralateral carotid artery was determined using a perivascular flow probe. The physiological parameters of mice were monitored throughout the experiments. The morphology and localization of the pial collaterals between the anterior and middle cerebral arteries were evaluated after staining of the cerebral vasculature.
Results
Neither the mean arterial blood pressure nor the arterial blood gas and acid-base parameters were different between the wild-type and VDRΔ/Δ mice. In spite of the unaltered physiological parameters, VDR deficiency compromised the cerebrovascular adaptation to unilateral CAO characterized by reduced cerebrocortical blood flow in the parietal and temporal regions of the ipsilateral hemispheres. The temporal cortex of VDRΔ/Δ mice showed the most pronounced drop and delayed recovery following CAO. Surprisingly, VDR deficiency had no significant influence on the contralateral carotid arterial blood flow increase, however, it decreased the number and increased the tortuosity of pial collaterals and altered their localization.
Conclusion
VDR deficiency results in diminished adaptation to unilateral CAO with the most sustained consequences in the temporal region. The latter may be attributed to the impaired development of pial collaterals, whereas the extracranial collateral circulation may not be compromised by VDR deficiency. These results may emphasize the importance of vitamin D signaling in normal cerebrovascular development and in the prevention of cerebrovascular disorders.

Funding: ÚNKP-20-4-I-SE-19, NKFIH K-125174

University and Doctoral School

Semmelweis University, Doctoral School of Theoretical and Translational Medicine