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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doaj-5520d18fbf434d10aa1b73da6268995a2020-11-25T03:10:57ZengMDPI AGBrain Sciences2076-34252020-05-011033533510.3390/brainsci10060335The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial AneurysmMieko Oka0Isao Ono1Kampei Shimizu2Mika Kushamae3Haruka Miyata4Takakazu Kawamata5Tomohiro Aoki6Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Osaka 564-8565, JapanDepartment of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Osaka 564-8565, JapanDepartment of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Osaka 564-8565, JapanDepartment of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Osaka 564-8565, JapanDepartment of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Osaka 564-8565, JapanDepartment of Neurosurgery, Tokyo Women’s Medical University, Tokyo 162-8666, JapanDepartment of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Osaka 564-8565, JapanConsidering 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. -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.https://www.mdpi.com/2076-3425/10/6/335intracranial aneurysmsubarachnoid hemorrhageestrogenfemaleendothelial cellmacrophage |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mieko Oka Isao Ono Kampei Shimizu Mika Kushamae Haruka Miyata Takakazu Kawamata Tomohiro Aoki |
spellingShingle |
Mieko Oka Isao Ono Kampei Shimizu Mika Kushamae Haruka Miyata Takakazu Kawamata Tomohiro Aoki The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm Brain Sciences intracranial aneurysm subarachnoid hemorrhage estrogen female endothelial cell macrophage |
author_facet |
Mieko Oka Isao Ono Kampei Shimizu Mika Kushamae Haruka Miyata Takakazu Kawamata Tomohiro Aoki |
author_sort |
Mieko Oka |
title |
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_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_sort |
bilateral ovariectomy in a female animal exacerbates the pathogenesis of an intracranial aneurysm |
publisher |
MDPI AG |
series |
Brain Sciences |
issn |
2076-3425 |
publishDate |
2020-05-01 |
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. -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. |
topic |
intracranial aneurysm subarachnoid hemorrhage estrogen female endothelial cell macrophage |
url |
https://www.mdpi.com/2076-3425/10/6/335 |
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