Cerebral Vascular Dysfunctions Detected in Human Small Vessel Disease and Implications for Preclinical Studies.

IF 15.7 1区 医学 Q1 PHYSIOLOGY Annual review of physiology Pub Date : 2022-02-10 DOI:10.1146/annurev-physiol-060821-014521
Joanna M Wardlaw, Helene Benveniste, Anna Williams
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引用次数: 16

Abstract

Cerebral small vessel disease (SVD) is highly prevalent and a common cause of ischemic and hemorrhagic stroke and dementia, yet the pathophysiology is poorly understood. Its clinical expression is highly varied, and prognostic implications are frequently overlooked in clinics; thus, treatment is currently confined to vascular risk factor management. Traditionally, SVD is considered the small vessel equivalent of large artery stroke (occlusion, rupture), but data emerging from human neuroimaging and genetic studies refute this, instead showing microvessel endothelial dysfunction impacting on cell-cell interactions and leading to brain damage. These dysfunctions reflect defects that appear to be inherited and secondary to environmental exposures, including vascular risk factors. Interrogation in preclinical models shows consistent and converging molecular and cellular interactions across the endothelial-glial-neural unit that increasingly explain the human macroscopic observations and identify common patterns of pathology despite different triggers. Importantly, these insights may offer new targets for therapeutic intervention focused on restoring endothelial-glial physiology.

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在人类小血管疾病中检测到的脑血管功能障碍及其临床前研究的意义。
脑血管病(SVD)非常普遍,是缺血性、出血性卒中和痴呆的常见病因,但其病理生理机制尚不清楚。其临床表现多种多样,其预后影响在临床上经常被忽视;因此,目前的治疗仅限于血管危险因素管理。传统上,SVD被认为是相当于大动脉中风(闭塞、破裂)的小血管,但来自人类神经影像学和遗传学研究的数据反驳了这一点,而是显示微血管内皮功能障碍影响细胞间相互作用并导致脑损伤。这些功能障碍反映了似乎是遗传的和继发于环境暴露的缺陷,包括血管危险因素。临床前模型的询问显示,内皮-胶质-神经单元之间的分子和细胞相互作用一致且趋同,这越来越多地解释了人类宏观观察结果,并确定了不同触发因素下的常见病理模式。重要的是,这些见解可能为专注于恢复内皮-神经胶质生理的治疗干预提供新的靶点。
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来源期刊
Annual review of physiology
Annual review of physiology 医学-生理学
CiteScore
35.60
自引率
0.00%
发文量
41
期刊介绍: Since 1939, the Annual Review of Physiology has been highlighting significant developments in animal physiology. The journal covers diverse areas, including cardiovascular physiology, cell physiology, ecological, evolutionary, and comparative physiology, endocrinology, gastrointestinal physiology, neurophysiology, renal and electrolyte physiology, respiratory physiology, and special topics.
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