Hu Xiaoming, De Silva T Michael, Chen Jun, Faraci Frank M
From the Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh School of Medicine, PA (X.H., J.C.); Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia (T.M.D.S.); and Departments of Internal Medicine and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City Veterans Affairs Healthcare System (F.M.F.).
Circ Res. 2017 Feb 3;120(3):449-471. doi: 10.1161/CIRCRESAHA.116.308427.
The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury after ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in blood-brain barrier integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events.
脑血管疾病的后果是全球主要的健康问题之一。大脑大血管和小血管疾病均可引发中风，并导致其他形式的神经功能障碍和退化的血管因素。这两种血管疾病均由多种风险因素驱动，其中高血压是主要因素。尽管神经血管疾病以及缺血事件后的后续损伤很重要，但这些领域的基础知识仍落后于我们目前对神经保护和一般血管生物学的理解。本综述的目的是探讨血管系统中促进灌注不足和缺血的特定关键结构和功能变化，同时也影响损伤程度和治疗效果。此外，由于血脑屏障受损是缺血的主要后果之一，我们讨论了缺血诱导的血脑屏障完整性和功能变化的细胞和分子机制，包括内皮细胞的改变以及周细胞、免疫细胞和基质金属蛋白酶的作用。识别在缺血前后控制血管变化的细胞类型、途径和分子，可能会产生新的方法来减缓脑血管疾病的进展，并减少缺血事件的发生频率和影响。
