PhD Scientific Days 2022

Translational Medicine III.

Vitamin D deficiency impairs cerebrovascular adaptation to carotid artery occlusion in ovariectomized mice

Text of the abstract

Introduction: The increased risk of cerebrovascular disorders has recently been associated with vitamin D deficiency. According to our previous results, vitamin D receptor deficiency in males impairs the cerebrovascular adaptation to unilateral common carotid artery occlusion (CAO), a common cause of ischemic stroke. However, the impact of gender (i.e. sex steroids) on the cerebrovascular consequences of vitamin D deficiency is still obscure.
Aims: We aimed to investigate the simultaneous effect of vitamin D receptor deficiency and female reproductive hormonal changes on the adaptation to CAO in an ovariectomized, vitamin D receptor deficient mouse model.
Methods: Vitamin D receptor deficient (VDR-KO) and wild-type (WT) adult female mice were subjected to bilateral ovariectomy (OVX). After five weeks, cerebrocortical blood flow (CoBF) changes following CAO were measured using laser speckle imaging under anaesthesia. The CoBF was registered in 4 cortical regions (frontal, parietal, temporal, and zone of pial anastomoses). Physiological parameters (blood pressure, oxygen saturation) were monitored during the experiments.
Results: Unlike in males, no significant difference was detected in the compensation to reduced blood flow after CAO in intact VDR-KO female mice compared to the intact WT animals. In contrast, OVX caused a delayed recovery in the zone of pial anastomoses in VDR-KO mice compared to WTs. Additionally, in the temporal region the ovariectomized VDR-KO mice suffered a significantly prolonged reduction in blood flow compared to intact VDR-KO mice and ovariectomized WTs.
Conclusion: These results indicate that the female gender is more protected from cerebrovascular disorders than males. Although OVX impaired the recovery of CoBF after CAO in VDR-KO mice, surprisingly, it did not aggravate the adaptational capacity to the extent previously observed in VDR-KO males. Thus, the less vulnerability of females to vitamin D deficiency compared to males is likely to be due to the lower concentrations of androgen hormones rather than the presence of estrogens.
Funding: EFOP-3.6.3-VEKOP-16-2017-00009; OTKA K-125174, K-139230