Age is an important risk factor of stroke, cognitive decline, and dementia. Senescent endothelial cells (ECs) accumulate with advancing age through exposure to cellular stress, such as that exerted by hypertension and diabetes. These senescent ECs have altered characteristics, such as altered tight junction proteins, use of a more indiscriminate transcellular transport system, increased inflammation, and increased immune cell interactions. ECs are the main component of the blood-brain barrier (BBB), separating the brain from systemic circulation. As senescent ECs accumulate in the BBB, their altered functioning results in the disruption of the barrier. They have inadequate barrier-forming properties, disrupted extracellular matrix, and increased transcytosis, resulting in an overly permeable barrier. This disruption of the BBB can have important effects in stroke and cognitive impairment, as presented in this review. Besides increasing the permeability of the BBB, senescent ECs can also impair angiogenesis and vascular remodeling, which in ischemic stroke may increase risk of hemorrhagic transformation and worsen outcomes. Senescent ECs may also contribute to microvascular dysfunction, with disruption of cerebral perfusion and autoregulation. These may contribute to vascular cognitive impairment along with increased permeability. With an aging population, there is growing interest in targeting senescence. Several ongoing trials have been evaluating whether senolytics can slow aging, improve vascular health, and reduce the risk of stroke and cognitive decline.

中文翻译：

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内皮细胞衰老对中风和认知障碍中血脑屏障的影响。


年龄是中风、认知能力下降和痴呆的重要危险因素。衰老的内皮细胞 （EC） 随着年龄的增长而通过暴露于细胞压力（例如高血压和糖尿病所施加的压力）而积累。这些衰老的 EC 具有改变的特性，例如紧密连接蛋白改变、使用更不加区分的跨细胞运输系统、炎症增加和免疫细胞相互作用增加。EC 是血脑屏障 （BBB） 的主要组成部分，将大脑与体循环分开。随着衰老的 ECs 在 BBB 中积累，它们的功能改变导致屏障被破坏。它们的屏障形成特性不足，细胞外基质被破坏，转胞吞作用增加，导致屏障过度渗透。如本综述所述，这种 BBB 的破坏可能对中风和认知障碍产生重要影响。除了增加 BBB 的通透性外，衰老 EC 还会损害血管生成和血管重塑，这在缺血性中风中可能会增加出血转化的风险并恶化结果。衰老的 ECs 也可能导致微血管功能障碍，破坏脑灌注和自动调节。这些可能导致血管性认知障碍以及通透性增加。随着人口老龄化，人们对靶向衰老的兴趣越来越大。几项正在进行的试验一直在评估 senolytics 是否可以延缓衰老、改善血管健康以及降低中风和认知能力下降的风险。