PhD Scientific Days 2023

Translational Medicine III.

Hyperandrogenism and Estrogen Deprivation Related Impairments in the Cerebrovascular Adaptation to Carotid Artery Occlusion in Vitamin D Receptor Deficient Female Mice

Előadó neve

Dr. Pál, Éva, PhD

Neptun code

GEXJT7

Előadó munkahelye

Institute of Translational Medicine, Semmelweis University

Előadó telefonszáma

+36703304702

Előadó e-mail címe

pal.eva@med.semmelweis-univ.hu

Az előadás címe

Hyperandrogenism and Estrogen Deprivation Related Impairments in the Cerebrovascular Adaptation to Carotid Artery Occlusion in Vitamin D Receptor Deficient Female Mice

Szerző(k) neve és munkahelye

Éva Pál1,2, Dorina Nagy1, László Hricisák1,2, Guillaume Peter Walford1, Gábor Karácsony1, Szabolcs Várbíró3, Zoltán Benyó1,2

1 Institute of Translational Medicine, Semmelweis University, Budapest
2 Eötvös Lóránd Research Network, Semmelweis University (ELKH-SU), Cerebrovascular and Neurocognitive Disorders Research Group, Budapest
3 Department of Obstetrics and Gynecology, Semmelweis University, Budapest

Bemutatás módja

Szóbeli

Szekció

Translational Medicine III.

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: Cerebrovascular diseases belong to the leading causes of death and disability worldwide. Among several risk factors, vitamin D deficiency and altered sex hormone status (i.e. menopause or hyperandrogenism) may increase the risk and severity of cerebrovascular disorders.

Aims: We aimed to analyse the combined effects of vitamin D receptor (VDR) deficiency and androgen excess/estrogen deprivation on the cerebrovascular adaptation to unilateral carotid artery occlusion (CAO), a common cause of ischemic stroke.

Methods: Experiments were performed on adult female mice carrying a functionally inactive VDR (VDR∆/∆) and wild-type (WT) littermates. The mice were assigned to six experimental groups: intact controls (WT, VDR∆/∆), ovariectomized (OVX-WT, OVX-VDR∆/∆) and testosterone treated (TT-WT, TT-VDR∆/∆) groups. The ovaries were removed five weeks before the in vivo cerebrocortical blood flow (CoBF) measurements and similarly, testosterone treated mice received transdermal treatment for five weeks before them. The CoBF changes after CAO were analysed in three cerebrocortical regions (frontal, parietal, temporal) in both hemispheres using in vivo laser speckle imaging. Physiological parameters of mice were determined during and after the CoBF measurements.

Results: Physiological parameters (arterial blood pressure, blood gas and acid-base values) did not differ between the groups. The CoBF of the contralateral regions following CAO was not affected by the absence of VDR signaling or androgen excess/estrogen deprivation. On the contrary, in the ipsilateral hemisphere, TT-VDR∆/∆ mice had the most delayed recovery after CAO in all regions. In the frontal region, TT-VDR∆/∆ mice had a significantly higher perfusion deficit compared to WT, VDR∆/∆, and OVX-WT mice. Similarly, TT-VDR∆/∆ mice suffered from the most prolonged hypoperfusion compared to WT and VDR∆/∆ mice in the parietal region, as well as to WT and OVX-WT mice in the temporal region.

Conclusion: Surprisingly, ovariectomy did not undermine the compensatory mechanisms after CAO in VDR deficient mice. Androgen excess with VDR deficiency resulted in a prolonged hypoperfusion in all regions of the ipsilateral cortex, which implies a vasoregulatory dysfunction that may aggravate the outcome of an ischemic stroke.

Funding: ÚNKP-22-4-II-SE-17, PD-143327, K-125174, K-139230, EFOP-3.6.3-VEKOP-16-2017-00009

University and Doctoral School

Semmelweis University, Doctoral School of Theoretical and Translational Medicine

Supervisor

-

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

2855

Start

14:45

End

15:00

Authors (legacy)

Éva Pál1,2, Dorina Nagy1, László Hricisák1,2, Guillaume Peter Walford1, Gábor Karácsony1, Szabolcs Várbíró3, Zoltán Benyó1,2

1 Institute of Translational Medicine, Semmelweis University, Budapest
2 Eötvös Lóránd Research Network, Semmelweis University (ELKH-SU), Cerebrovascular and Neurocognitive Disorders Research Group, Budapest
3 Department of Obstetrics and Gynecology, Semmelweis University, Budapest