Memory Clinic, Department of Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, 150 06 Prague, Czech Republic.
International Clinical Research Centre, St. Anne's University Hospital, 656 91 Brno, Czech Republic.
Int J Mol Sci. 2019 May 15;20(10):2405. doi: 10.3390/ijms20102405.
Vascular cognitive impairment (VCI) is the second most common cause of cognitive deficit after Alzheimer's disease. Since VCI patients represent an important target population for prevention, an ongoing effort has been made to elucidate the pathogenesis of this disorder. In this review, we summarize the information from animal models on the molecular changes that occur in the brain during a cerebral vascular insult and ultimately lead to cognitive deficits in VCI. Animal models cannot effectively represent the complex clinical picture of VCI in humans. Nonetheless, they allow some understanding of the important molecular mechanisms leading to cognitive deficits. VCI may be caused by various mechanisms and metabolic pathways. The pathological mechanisms, in terms of cognitive deficits, may span from oxidative stress to vascular clearance of toxic waste products (such as amyloid beta) and from neuroinflammation to impaired function of microglia, astrocytes, pericytes, and endothelial cells. Impaired production of elements of the immune response, such as cytokines, and vascular factors, such as insulin-like growth factor 1 (IGF-1), may also affect cognitive functions. No single event could be seen as being the unique cause of cognitive deficits in VCI. These events are interconnected, and may produce cascade effects resulting in cognitive impairment.
血管性认知障碍（VCI）是仅次于阿尔茨海默病的第二大认知功能障碍病因。由于 VCI 患者是预防的重要目标人群，因此人们一直在努力阐明这种疾病的发病机制。在这篇综述中，我们总结了动物模型中关于脑血管损伤时大脑中发生的分子变化的信息，这些变化最终导致 VCI 中的认知功能障碍。动物模型不能有效地代表 VCI 在人类中的复杂临床情况。尽管如此，它们还是让我们对导致认知功能障碍的重要分子机制有了一些了解。VCI 可能由多种机制和代谢途径引起。从氧化应激到血管清除毒性废物（如淀粉样β），从神经炎症到小胶质细胞、星形胶质细胞、周细胞和内皮细胞功能受损，再到认知缺陷的病理机制。免疫反应的元素（如细胞因子）和血管因子（如胰岛素样生长因子 1（IGF-1））的产生受损也可能影响认知功能。没有一个单一的事件可以被视为 VCI 中认知功能障碍的唯一原因。这些事件相互关联，并可能产生级联效应，导致认知障碍。
