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The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm

Considering the poor outcome of subarachnoid hemorrhage (SAH) due to the rupture of intracranial aneurysms (IA), mechanisms underlying the pathogenesis of IAs, especially the rupture of lesions, should be clarified. In the present study, a rat model of IAs in which induced lesions spontaneously rupt...

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Autores principales: Oka, Mieko, Ono, Isao, Shimizu, Kampei, Kushamae, Mika, Miyata, Haruka, Kawamata, Takakazu, Aoki, Tomohiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349062/
https://www.ncbi.nlm.nih.gov/pubmed/32486339
http://dx.doi.org/10.3390/brainsci10060335
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author Oka, Mieko
Ono, Isao
Shimizu, Kampei
Kushamae, Mika
Miyata, Haruka
Kawamata, Takakazu
Aoki, Tomohiro
author_facet Oka, Mieko
Ono, Isao
Shimizu, Kampei
Kushamae, Mika
Miyata, Haruka
Kawamata, Takakazu
Aoki, Tomohiro
author_sort Oka, Mieko
collection PubMed
description Considering the poor outcome of subarachnoid hemorrhage (SAH) due to the rupture of intracranial aneurysms (IA), mechanisms underlying the pathogenesis of IAs, especially the rupture of lesions, should be clarified. In the present study, a rat model of IAs in which induced lesions spontaneously ruptured resulting in SAH was used. In this model, the combination of the female sex and the bilateral ovariectomy increased the incidence of SAH, similar to epidemiological evidence in human cases. Importantly, unruptured IA lesions induced in female animals with bilateral ovariectomy were histopathologically similar to ruptured ones in the presence of vasa vasorum and the accumulation of abundant inflammatory cells, suggesting the exacerbation of the disease. The post-stenotic dilatation of the carotid artery was disturbed by the bilateral ovariectomy in female rats, which was restored by hormone replacement therapy. The in vivo study thus suggested the protective effect of estrogen from the ovary on endothelial cells loaded by wall shear stress. β-estradiol or dihydrotestosterone also suppressed the lipopolysaccharide-induced expression of pro-inflammatory genes in cultured macrophages and neutrophils. The results of the present study have thus provided new insights about the process regulating the progression of the disease.
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spelling pubmed-73490622020-07-22 The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm Oka, Mieko Ono, Isao Shimizu, Kampei Kushamae, Mika Miyata, Haruka Kawamata, Takakazu Aoki, Tomohiro Brain Sci Article Considering the poor outcome of subarachnoid hemorrhage (SAH) due to the rupture of intracranial aneurysms (IA), mechanisms underlying the pathogenesis of IAs, especially the rupture of lesions, should be clarified. In the present study, a rat model of IAs in which induced lesions spontaneously ruptured resulting in SAH was used. In this model, the combination of the female sex and the bilateral ovariectomy increased the incidence of SAH, similar to epidemiological evidence in human cases. Importantly, unruptured IA lesions induced in female animals with bilateral ovariectomy were histopathologically similar to ruptured ones in the presence of vasa vasorum and the accumulation of abundant inflammatory cells, suggesting the exacerbation of the disease. The post-stenotic dilatation of the carotid artery was disturbed by the bilateral ovariectomy in female rats, which was restored by hormone replacement therapy. The in vivo study thus suggested the protective effect of estrogen from the ovary on endothelial cells loaded by wall shear stress. β-estradiol or dihydrotestosterone also suppressed the lipopolysaccharide-induced expression of pro-inflammatory genes in cultured macrophages and neutrophils. The results of the present study have thus provided new insights about the process regulating the progression of the disease. MDPI 2020-05-31 /pmc/articles/PMC7349062/ /pubmed/32486339 http://dx.doi.org/10.3390/brainsci10060335 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Oka, Mieko
Ono, Isao
Shimizu, Kampei
Kushamae, Mika
Miyata, Haruka
Kawamata, Takakazu
Aoki, Tomohiro
The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm
title The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm
title_full The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm
title_fullStr The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm
title_full_unstemmed The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm
title_short The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm
title_sort bilateral ovariectomy in a female animal exacerbates the pathogenesis of an intracranial aneurysm
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349062/
https://www.ncbi.nlm.nih.gov/pubmed/32486339
http://dx.doi.org/10.3390/brainsci10060335
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