Research progress on the effect of hypercholesterolemia on neural function and cerebrovascular disease

doi:10.3969/j.issn.1672-6731.2021.02.008

Abstract

Abstract:

Cholesterol is an essential component for neural physiology. Cholesterol metabolism in brain is independent from that in peripheral tissues due to blood-brain barrier (BBB). In order to keep brain function well, the content of cholesterol in brain must be accurately maintained through close coordination between astrocyte, neurons and vascular endothelial cell, which are the three main components of neurovascular unit (NVU). Hypercholesterolemia is usually accompanied with increased permeability of BBB, activated astrocytes then upregulate the transcription of a series of cholesterol-related genes, leading to high expression of cholesterol transmembrane proteins, which destroy the stability of the cell-to-cell signal transduction between astrocyte and neuron, together with activated microglia releasing a large number of neuroinflammatory factors, triggering the neuroinflammatory response, and eventually lead to neuronal cell apoptosis. As a result, hypercholesterolemia related cognitive dysfunction is present. Vascular endothelial injury characterized by erythrocyte stasis, is an early manifestation of hypercholesterolemia on brain small vessels and capillaries, the appearance of fribi thrombi is a sign of the late stage of cerebral small vessel disease (CSVD), causing extensive occlusion of brain microvessels, resulting in decreased vascular density and cerebral blood flow. Hypercholesterolemia shows positive correlation with the characteristic features of CSVD on MRI, such as lacunar infarction, periventricular white matter hyperintensity and brain atrophy, but rarely with cerebral microbleeds (CMBs). With the advent of statins and their wide-spread application, the risk of stroke and its all-cause mortality decreased greatly around the world, which is mainly related to the significant decrease of plasma low density lipoprotein cholesterol (LDL-C) level caused by statins. However, there are still a number of controversial reports about the relationship with hypercholesterolemia, statin therapy and the risk of cerebral hemorrhage, thus, further work is needed.

Key words: Hypercholesterolemia, Neurons, Neuroglia, Blood-brain barrier, Cerebral small vessel diseases, Review

摘要：

胆固醇对维持脑组织正常生理功能十分重要，其表达水平的精准调控通过神经血管单元三要素（神经元、神经胶质细胞和血-脑屏障）的密切协同得以实现。高胆固醇血症通常伴随血-脑屏障通透性增加，激活的星形胶质细胞上调一系列胆固醇相关基因的转录，引起胆固醇跨膜转运蛋白高表达，破坏神经胶质细胞-神经元之间信号转导的稳定，连同小胶质细胞共同释放大量神经炎性因子，诱发神经炎症反应，最终导致神经细胞凋亡，临床表现为高胆固醇血症相关认知功能障碍。高胆固醇血症对脑小血管和微血管的影响主要是血管内皮细胞损伤，组织病理学早期出现红细胞淤积，晚期出现纤维素血栓，引起广泛的小血管闭塞。高胆固醇血症的MRI呈现腔隙性梗死、脑室周围白质高信号和脑萎缩等脑小血管病的特征性表现，很少出现脑微出血。他汀类调脂药极大降低脑卒中的风险和全因死亡率，主要与药物使血浆低密度脂蛋白胆固醇水平明显降低相关。但是关于高胆固醇血症、他汀类调脂药与脑出血风险之间的关系，目前仍有争议，尚待进一步研究。

关键词: 高胆固醇血症, 神经元, 神经胶质, 血脑屏障, 大脑小血管疾病, 综述

ZHUO Jie. Research progress on the effect of hypercholesterolemia on neural function and cerebrovascular disease[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2021, 21(2): 107-113.

卓杰. 高胆固醇血症对神经功能和脑血管病影响的研究进展[J]. 中国现代神经疾病杂志, 2021, 21(2): 107-113.

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