Disruption of Vitamin D Signaling Impairs Adaptation of Cerebrocortical Microcirculation to Carotid Artery Occlusion in Hyperandrogenic Female Mice.
Disruption of Vitamin D Signaling Impairs Adaptation of Cerebrocortical Microcirculation to Carotid Artery Occlusion in Hyperandrogenic Female Mice.
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DOI：
10.3390/nu15183869
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发表时间：
2023-09-05
期刊：
影响因子：
5.9
通讯作者：
Pál É
中科院分区：
文献类型：
--
作者：
Nagy D;Hricisák L;Walford GP;Lékai Á;Karácsony G;Várbíró S;Ungvári Z;Benyó Z;Pál É
维生素D缺乏导致与年龄相关的脑血管疾病，包括缺血性中风的发病机制。性激素状态也可能影响这些疾病的患病率，这表明绝经后和高雄激素妇女的脆弱性增加。为了研究性类固醇和破坏的维生素D信号在脑微循环中的潜在相互作用，我们研究了完整的，卵巢切除的，高雄激素雌性小鼠正常或功能不活跃的维生素D受体（VDR）的脑血管适应单侧颈动脉闭塞（CAO）。我们还分析了在代偿中起重要作用的软脑膜病变的形态学。尽管软脑膜侧支循环数量减少，但VDR消融本身并不影响大脑皮层对CAO的适应。虽然卵巢切除术并没有破坏CAO后的代偿机制，但雄激素过多与VDR不活动相结合导致闭塞同侧大脑皮质长期灌注不足。这些发现表明，VDR信号中断的脑血管后果在女性中不太明显，即使在卵巢切除术后也提供了一定程度的保护。相反，即使是短期雄激素过多，缺乏VDR信号可能导致缺血性卒中的不利结果，突出了性类固醇和维生素D在脑血管疾病方面的复杂相互作用。
Vitamin D deficiency contributes to the pathogenesis of age-related cerebrovascular diseases, including ischemic stroke. Sex hormonal status may also influence the prevalence of these disorders, indicated by a heightened vulnerability among postmenopausal and hyperandrogenic women. To investigate the potential interaction between sex steroids and disrupted vitamin D signaling in the cerebral microcirculation, we examined the cerebrovascular adaptation to unilateral carotid artery occlusion (CAO) in intact, ovariectomized, and hyperandrogenic female mice with normal or functionally inactive vitamin D receptor (VDR). We also analyzed the morphology of leptomeningeal anastomoses, which play a significant role in the compensation. Ablation of VDR by itself did not impact the cerebrocortical adaptation to CAO despite the reduced number of pial collaterals. While ovariectomy did not undermine compensatory mechanisms following CAO, androgen excess combined with VDR inactivity resulted in prolonged hypoperfusion in the cerebral cortex ipsilateral to the occlusion. These findings suggest that the cerebrovascular consequences of disrupted VDR signaling are less pronounced in females, providing a level of protection even after ovariectomy. Conversely, even short-term androgen excess with lacking VDR signaling may lead to unfavorable outcomes of ischemic stroke, highlighting the complex interplay between sex steroids and vitamin D in terms of cerebrovascular diseases.
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影响因子：
4.1
作者：
Boettger SF;Angersbach B;Klimek CN;Wanderley ALM;Shaibekov A;Sieske L;Wang B;Zuchowski M;Wirth R;Pourhassan M
通讯作者：
Pourhassan M
影响因子：
16.2
作者：
de Bresser J;Tiehuis AM;van den Berg E;Reijmer YD;Jongen C;Kappelle LJ;Mali WP;Viergever MA;Biessels GJ;Utrecht Diabetic Encephalopathy Study Group
通讯作者：
Utrecht Diabetic Encephalopathy Study Group
影响因子：
3
作者：
Brundel, Manon;van den Berg, Esther;Biessels, Geert Jan
通讯作者：
Biessels, Geert Jan
影响因子：
7.7
作者：
Brundel, Manon;Reijmer, Yael D.;Biessels, Geert Jan
通讯作者：
Biessels, Geert Jan
影响因子：
--
作者：
Erben, RG;Soegiarto, DW;Balling, R
通讯作者：
Balling, R