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衰老小鼠模型海马体血脑屏障通透性增加。

Increased permeability of blood-brain barrier on the hippocampus of a murine model of senescence.

作者信息

Pelegrí Carme, Canudas Anna Maria, del Valle Jaume, Casadesus Gemma, Smith Mark A, Camins Antoni, Pallàs Mercè, Vilaplana Jordi

机构信息

Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.

出版信息

Mech Ageing Dev. 2007 Sep;128(9):522-8. doi: 10.1016/j.mad.2007.07.002. Epub 2007 Jul 10.

DOI:10.1016/j.mad.2007.07.002
PMID:17697702
Abstract

SAMP8 mice show several indicative characteristics of accelerated aging and have been used to study the physiological and physiopathological processes that take place during senescence. There is some controversy about the presence of a functional blood-brain barrier (BBB) disturbance on these animals, which could be related to the oxidative stress or the amyloidosis present in their brain. In order to elucidate BBB status in the hippocampus of SAMP8 mice, in this study we have determined the extravasation from brain microvessels of endogenous IgG in SAMP8 mice aged 3, 7 and 12 months and in age-matched control SAMR1 mice. Immunohistochemistry, confocal microscopy and an imaging methodology specially designed to quantify IgG extravasation have been used. The choroid plexus was analyzed as a control for positive extravasation in SAMP8 and SAMR1 mice and, as expected, in all studied ages high IgG immunoreactivity was observed in both strains. We have found significantly higher levels of IgG extravasation in the hippocampus of 12-month-old SAMP8 mice compared to SAMR1 mice, indicating an increased permeability of BBB in aged senescence-accelerated mice.

摘要

SAMP8小鼠表现出加速衰老的若干指示性特征,并已被用于研究衰老过程中发生的生理和病理生理过程。关于这些动物是否存在功能性血脑屏障(BBB)紊乱存在一些争议,这可能与它们大脑中存在的氧化应激或淀粉样变性有关。为了阐明SAMP8小鼠海马体中的血脑屏障状态,在本研究中,我们测定了3个月、7个月和12个月龄的SAMP8小鼠以及年龄匹配的对照SAMR1小鼠脑微血管内源性IgG的外渗情况。我们使用了免疫组织化学、共聚焦显微镜以及专门设计用于量化IgG外渗的成像方法。脉络丛作为SAMP8和SAMR1小鼠阳性外渗的对照进行了分析,正如预期的那样,在所有研究年龄中,两种品系均观察到高IgG免疫反应性。我们发现,与SAMR1小鼠相比,12个月龄SAMP8小鼠海马体中的IgG外渗水平显著更高,这表明衰老加速小鼠的血脑屏障通透性增加。

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