Bravo-Ferrer Isabel, Gaasdal-Bech Katrine, Colvin Chiara, Vaughan Hollie J, Moss Jonathan, Williams Anna, Díaz Castro Blanca
Centre for Discovery Brain Sciences, The University of Edinburgh, Edinburgh EH16 4SB, UK.
UK Dementia Research Institute at the University of Edinburgh, Edinburgh EH16 4SB, UK.
Brain Commun. 2025 Sep 10;7(5):fcaf332. doi: 10.1093/braincomms/fcaf332. eCollection 2025.
Age-associated vascular alterations make the brain more vulnerable to neuropathologies. Research in humans and rodents has demonstrated structural, molecular, and functional alterations of the aged brain vasculature that suggest blood-brain barrier dysfunction. However, these studies focused on particular features of the blood-brain barrier and specific brain regions. Thus, it remains unclear if and which blood-brain barrier age-associated phenotypes are conserved across brain areas. Moreover, there is very limited information about how blood-brain barrier dysfunction and cell-specific phenotypes relate to each other. In this manuscript, we use immunofluorescence, transmission electron microscopy, and permeability assays to assess how age-associated blood-brain barrier molecular, structural, and functional phenotypes correlate between the blood-brain barrier cell types at three brain regions (prefrontal cortex, hippocampus, and corpus callosum) during mouse early ageing. We discovered that at 18-20 months of age, changes to the mouse blood-brain barrier are subtle. The prefrontal cortex blood-brain barrier is the most affected by age, with alterations in brain endothelial cell protein expression, blood-brain barrier permeability, basement membrane thickness, and astrocyte endfoot size when compared with young mice. Here, we deliver a detailed multicellular characterization of region-dependent blood-brain barrier changes at early stages of ageing. Our data paves the way for future studies to investigate how region-specific blood-brain barrier dysfunction may contribute to disease-associated regional vulnerability.
与年龄相关的血管改变使大脑更容易受到神经病理学的影响。对人类和啮齿动物的研究表明，老年脑血管系统存在结构、分子和功能改变，提示血脑屏障功能障碍。然而，这些研究集中在血脑屏障的特定特征和特定脑区。因此，目前尚不清楚血脑屏障与年龄相关的表型是否以及哪些在不同脑区是保守的。此外，关于血脑屏障功能障碍与细胞特异性表型之间如何相互关联的信息非常有限。在本论文中，我们使用免疫荧光、透射电子显微镜和通透性测定法，来评估在小鼠早期衰老过程中，与年龄相关的血脑屏障分子、结构和功能表型在三个脑区（前额叶皮层、海马体和胼胝体）的血脑屏障细胞类型之间是如何相关的。我们发现，在18 - 20个月大时，小鼠血脑屏障的变化很细微。与年轻小鼠相比，前额叶皮层血脑屏障受年龄影响最大，表现为脑内皮细胞蛋白表达、血脑屏障通透性、基底膜厚度和星形胶质细胞终足大小的改变。在这里，我们对衰老早期阶段区域依赖性血脑屏障变化进行了详细的多细胞特征描述。我们的数据为未来研究区域特异性血脑屏障功能障碍如何导致疾病相关的区域易损性铺平了道路。
