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高龄产妇对老年大鼠缺血性中风易感性的影响:血脑屏障通透性和基因表达研究

Effect of advanced maternal age on ischemic stroke vulnerability in aged rats: Investigating on blood-brain barrier permeability and gene expression.

作者信息

Khayat Samira, Fanaei Hamed

机构信息

Pregnancy Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

Department of Midwifery, School of Nursing and Midwifery, Zahedan University of Medical Sciences, Zahedan, Iran.

出版信息

Aging Brain. 2024 Sep 11;6:100125. doi: 10.1016/j.nbas.2024.100125. eCollection 2024.

DOI:10.1016/j.nbas.2024.100125
PMID:39309404
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11415947/
Abstract

BACKGROUND

Advanced maternal age (AMA), commonly defined as pregnancy at or above 35 years old. Based on the evidence, this trend has raised concerns about potential health consequences for mothers, particularly in relation to ischemic stroke. Studies suggest that AMA may be associated with a higher risk of ischemic stroke in women due to physiological changes that impact vascular health and increase cardiovascular risk factors. The aim of this study was to investigate the effect of AMA on the extent of damage after ischemic stroke in aged rats.

METHODS

Female rats that gave birth at an old age (10 months) and at a young age (4 months) were subjected to ischemic stroke in old age (20 months) and subsequently compared.We assessed neurological deficits, infarct volume, blood-brain barrier (BBB) permeability, TNF-alpha levels, total oxidant capacity, and gene expressions that play a role in BBB integrity (VEGF, Occludin, and MMP-9) following ischemic stroke.

RESULTS

There were significantly elevated levels of MMP-9 expression and reduced levels of occludin in AMA rats. Additionally, AMA rats had significantly higher levels of TNF-alpha and total oxidant capacity after experiencing an ischemic stroke. AMA rats showed significantly higher brain water content (BBB permeability), infarct volume, and neurological deficits compared to young-aged pregnancies.

DISCUSSION

Complex relationship between pregnancy-related physiological changes, aging, vascular gene expression, and inflammatory factors may play a role in the increased vulnerability observed in older pregnant rats. The similarities between pregnancy-related alterations and aging highlight the influence of advanced maternal age on susceptibility to ischemic stroke.

摘要

背景

高龄产妇(AMA)通常定义为年龄在35岁及以上的孕妇。根据现有证据,这种趋势引发了人们对母亲潜在健康后果的担忧,尤其是与缺血性中风相关的后果。研究表明,由于生理变化影响血管健康并增加心血管危险因素,AMA可能与女性缺血性中风风险较高有关。本研究的目的是调查AMA对老年大鼠缺血性中风后损伤程度的影响。

方法

将老年(10个月)和年轻(4个月)分娩的雌性大鼠在老年(20个月)时进行缺血性中风,随后进行比较。我们评估了缺血性中风后神经功能缺损、梗死体积、血脑屏障(BBB)通透性、肿瘤坏死因子-α水平、总氧化能力以及在BBB完整性中起作用的基因表达(血管内皮生长因子、闭合蛋白和基质金属蛋白酶-9)。

结果

AMA大鼠中基质金属蛋白酶-9表达水平显著升高,闭合蛋白水平降低。此外,AMA大鼠在经历缺血性中风后肿瘤坏死因子-α和总氧化能力水平显著更高。与年轻妊娠大鼠相比,AMA大鼠的脑含水量(BBB通透性)、梗死体积和神经功能缺损显著更高。

讨论

与妊娠相关的生理变化、衰老、血管基因表达和炎症因子之间的复杂关系可能在老年妊娠大鼠中观察到的易感性增加中起作用。与妊娠相关的改变和衰老之间的相似性突出了高龄产妇对缺血性中风易感性的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38da/11415947/af399cb849a0/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38da/11415947/fc0fff9ab47b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38da/11415947/c93477159a2e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38da/11415947/7f884e3a41a2/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38da/11415947/af399cb849a0/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38da/11415947/fc0fff9ab47b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38da/11415947/c93477159a2e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38da/11415947/7f884e3a41a2/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38da/11415947/af399cb849a0/gr4.jpg

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