17β-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood–Brain Barrier Injury and Oxidative Stress Through SRC3-Mediated PI3K/Akt Signaling Pathway in a Mouse Model

17β-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood–Brain Barrier Injury and Oxidative Stress Through SRC3-Mediated PI3K/Akt Signaling Pathway in a Mouse Model

Estrogen is neuroprotective in brain injury models, and steroid receptor cofactor 3 (SRC3) mediates estrogen signaling. We aimed to investigate whether and how SRC3 is involved in the neuroprotective effects of 17ß-estradiol (E2) in a mouse model of intracerebral hemorrhage (ICH). Ovariectomized fem...

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Main Authors: Han Xiao, Jianyang Liu, Jialin He, Ziwei Lan, Mingyang Deng, Zhiping Hu
Format: Article
Language:English
Published: SAGE Publishing 2021-09-01
Series:ASN Neuro
Online Access:https://doi.org/10.1177/17590914211038443
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spelling doaj-adf8b556172f4b7e91676591749db6322021-09-21T16:12:09ZengSAGE PublishingASN Neuro1759-09142021-09-011310.1177/1759091421103844317β-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood–Brain Barrier Injury and Oxidative Stress Through SRC3-Mediated PI3K/Akt Signaling Pathway in a Mouse ModelHan Xiao0Jianyang Liu1Jialin He2Ziwei Lan3Mingyang Deng4Zhiping Hu5 Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha, China Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha, China Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha, China Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha, China Department of Hematology, the Second Xiangya Hospital, Central South University, Changsha, China Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha, ChinaEstrogen is neuroprotective in brain injury models, and steroid receptor cofactor 3 (SRC3) mediates estrogen signaling. We aimed to investigate whether and how SRC3 is involved in the neuroprotective effects of 17ß-estradiol (E2) in a mouse model of intracerebral hemorrhage (ICH). Ovariectomized female mice were treated with E2 after autologous blood injection-induced ICH. Brain damage was assessed by neurological deficit score, brain water content, and oxidative stress levels. Blood–brain barrier (BBB) integrity was evaluated by Evan's blue extravasation and claudin-5, ZO-1, and occludin levels. SRC3 expression and PI3K/Akt signaling pathway were examined in ICH mice treated with E2. The effect of SRC3 on E2-mediated neuroprotection was determined by examining neurological outcomes in SRC3-deficient mice undergone ICH and E2 treatment. We found that E2 alleviated ICH-induced brain edema and neurological deficits, protected BBB integrity, and suppressed oxidative stress. E2 enhanced SRC3 expression and PI3K-/Akt signaling pathway. SRC3 deficiency abolished the protective effects of E2 on ICH-induced neurological deficits, brain edema, and BBB integrity. Our results suggest that E2 suppresses ICH-induced brain injury and SRC3 plays a critical role in E2-mediated neuroprotection.https://doi.org/10.1177/17590914211038443
collection DOAJ
language English
format Article
sources DOAJ
author Han Xiao
Jianyang Liu
Jialin He
Ziwei Lan
Mingyang Deng
Zhiping Hu
spellingShingle Han Xiao
Jianyang Liu
Jialin He
Ziwei Lan
Mingyang Deng
Zhiping Hu
17β-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood–Brain Barrier Injury and Oxidative Stress Through SRC3-Mediated PI3K/Akt Signaling Pathway in a Mouse Model
ASN Neuro
author_facet Han Xiao
Jianyang Liu
Jialin He
Ziwei Lan
Mingyang Deng
Zhiping Hu
author_sort Han Xiao
title 17β-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood–Brain Barrier Injury and Oxidative Stress Through SRC3-Mediated PI3K/Akt Signaling Pathway in a Mouse Model
title_short 17β-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood–Brain Barrier Injury and Oxidative Stress Through SRC3-Mediated PI3K/Akt Signaling Pathway in a Mouse Model
title_full 17β-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood–Brain Barrier Injury and Oxidative Stress Through SRC3-Mediated PI3K/Akt Signaling Pathway in a Mouse Model
title_fullStr 17β-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood–Brain Barrier Injury and Oxidative Stress Through SRC3-Mediated PI3K/Akt Signaling Pathway in a Mouse Model
title_full_unstemmed 17β-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood–Brain Barrier Injury and Oxidative Stress Through SRC3-Mediated PI3K/Akt Signaling Pathway in a Mouse Model
title_sort 17β-estradiol attenuates intracerebral hemorrhage-induced blood–brain barrier injury and oxidative stress through src3-mediated pi3k/akt signaling pathway in a mouse model
publisher SAGE Publishing
series ASN Neuro
issn 1759-0914
publishDate 2021-09-01
description Estrogen is neuroprotective in brain injury models, and steroid receptor cofactor 3 (SRC3) mediates estrogen signaling. We aimed to investigate whether and how SRC3 is involved in the neuroprotective effects of 17ß-estradiol (E2) in a mouse model of intracerebral hemorrhage (ICH). Ovariectomized female mice were treated with E2 after autologous blood injection-induced ICH. Brain damage was assessed by neurological deficit score, brain water content, and oxidative stress levels. Blood–brain barrier (BBB) integrity was evaluated by Evan's blue extravasation and claudin-5, ZO-1, and occludin levels. SRC3 expression and PI3K/Akt signaling pathway were examined in ICH mice treated with E2. The effect of SRC3 on E2-mediated neuroprotection was determined by examining neurological outcomes in SRC3-deficient mice undergone ICH and E2 treatment. We found that E2 alleviated ICH-induced brain edema and neurological deficits, protected BBB integrity, and suppressed oxidative stress. E2 enhanced SRC3 expression and PI3K-/Akt signaling pathway. SRC3 deficiency abolished the protective effects of E2 on ICH-induced neurological deficits, brain edema, and BBB integrity. Our results suggest that E2 suppresses ICH-induced brain injury and SRC3 plays a critical role in E2-mediated neuroprotection.
url https://doi.org/10.1177/17590914211038443
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AT jianyangliu 17bestradiolattenuatesintracerebralhemorrhageinducedbloodbrainbarrierinjuryandoxidativestressthroughsrc3mediatedpi3kaktsignalingpathwayinamousemodel
AT jialinhe 17bestradiolattenuatesintracerebralhemorrhageinducedbloodbrainbarrierinjuryandoxidativestressthroughsrc3mediatedpi3kaktsignalingpathwayinamousemodel
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AT mingyangdeng 17bestradiolattenuatesintracerebralhemorrhageinducedbloodbrainbarrierinjuryandoxidativestressthroughsrc3mediatedpi3kaktsignalingpathwayinamousemodel
AT zhipinghu 17bestradiolattenuatesintracerebralhemorrhageinducedbloodbrainbarrierinjuryandoxidativestressthroughsrc3mediatedpi3kaktsignalingpathwayinamousemodel
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