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

doi:10.3390/brainsci10060335

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

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Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Osaka 564-8565, Japan

Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka 564-8565, Japan

Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo 162-8666, Japan

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Department of Neurosurgery, Kyoto University Graduate School of Medicine, Tokyo 606-8507, Japan

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Department of Neurosurgery, Showa University, Tokyo 142-8666, Japan

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Department of Neurosurgery, Shiga University of Medical Science, Shiga 520-2192, Japan

Author to whom correspondence should be addressed.

Brain Sci. 2020, 10(6), 335; https://doi.org/10.3390/brainsci10060335

Received: 24 April 2020 / Revised: 23 May 2020 / Accepted: 28 May 2020 / Published: 31 May 2020

(This article belongs to the Special Issue Experimental and Clinical Treatment of Subarachnoid Hemorrhage after Rupture of Saccular Intracranial Aneurysms)

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Abstract

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. View Full-Text

Keywords: intracranial aneurysm; subarachnoid hemorrhage; estrogen; female; endothelial cell; macrophage

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MDPI and ACS Style

Oka, M.; Ono, I.; Shimizu, K.; Kushamae, M.; Miyata, H.; Kawamata, T.; Aoki, T. The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm. Brain Sci. 2020, 10, 335. https://doi.org/10.3390/brainsci10060335

AMA Style

Oka M, Ono I, Shimizu K, Kushamae M, Miyata H, Kawamata T, Aoki T. The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm. Brain Sciences. 2020; 10(6):335. https://doi.org/10.3390/brainsci10060335

Chicago/Turabian Style

Oka, Mieko, Isao Ono, Kampei Shimizu, Mika Kushamae, Haruka Miyata, Takakazu Kawamata, and Tomohiro Aoki. 2020. "The Bilateral Ovariectomy in a Female Animal Exacerbates the Pathogenesis of an Intracranial Aneurysm" Brain Sciences 10, no. 6: 335. https://doi.org/10.3390/brainsci10060335

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