Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences; UK Dementia Research Institute; and Edinburgh Imaging, University of Edinburgh, Edinburgh, United Kingdom; email:
Department of Anesthesiology, Yale School of Medicine, New Haven, Connecticut, USA.
Annu Rev Physiol. 2022 Feb 10;84:409-434. doi: 10.1146/annurev-physiol-060821-014521. Epub 2021 Oct 26.
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.
脑小血管病（SVD）患病率高，是缺血性卒中和出血性卒中和痴呆的常见病因，但发病机制尚不清楚。其临床表现多种多样，临床往往忽略其预后意义，因此目前的治疗仅限于血管危险因素管理。传统上，SVD 被认为是与大动脉卒中等效的小血管病变（闭塞、破裂），但来自人类神经影像学和遗传研究的数据对此提出了质疑，而是显示微血管内皮功能障碍影响细胞-细胞相互作用，导致脑损伤。这些功能障碍反映了似乎是遗传的缺陷，并继发于环境暴露，包括血管危险因素。在临床前模型中的研究表明，内皮-胶质-神经单元之间存在一致和趋同的分子和细胞相互作用，这些相互作用越来越多地解释了人类的宏观观察结果，并确定了尽管触发因素不同但具有共同病理模式。重要的是，这些见解可能为以恢复内皮-胶质生理学为目标的治疗干预提供新的靶点。
