University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, United Kingdom.
Bristol Renal, Bristol Heart Institute, Translational Health Sciences, Bristol Medical School, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, United Kingdom.
Brain Res. 2022 Apr 1;1780:147804. doi: 10.1016/j.brainres.2022.147804. Epub 2022 Jan 29.
The socio-economic impact of diseases associated with cognitive impairment is increasing. According to the Alzheimer's Society there are over 850,000 people with dementia in the UK, costing the UK £26 billion in 2013. Therefore, research into treatment of those conditions is vital. Research into the cerebral endothelial glycocalyx (CeGC) could offer effective treatments. The CeGC, consisting of proteoglycans, glycoproteins and glycolipids, is a dynamic structure covering the luminal side oftheendothelial cells of capillaries throughout the body. The CeGC is thicker in cerebral micro vessels, suggesting specialisation for its function as part of the blood-brain barrier (BBB). Recent research evidences that the CeGC is vital in protecting fragile parenchymal tissue and effective functioning of the BBB, as one particularly important CeGC function is to act as a protective barrier and permeability regulator. CeGC degradation is one of the factors which can lead to an increase in BBB permeability. It occurs naturally in aging, nevertheless, premature degradationhas beenevidencedin multipleconditions linked to cognitive impairment, such as inflammation,brain edema, cerebral malaria, Alzheimer's and recently Covid-19. Increasing knowledge of the mechanisms of CeGC damage has led to research into preventative techniques showing that CeGC is a possible diagnostic marker and a therapeutic target. However, the evidence is relatively new, inconsistent and demonstrated mainly in experimental models. This review evaluates the current knowledge of the CeGC, its structure, functions, damage and repair mechanisms and the impact of its degeneration on cognitive impairment in multiple conditions, highlighting the CeGC as a possible diagnostic marker and a potential target for therapeutic treatment.
与认知障碍相关的疾病的社会经济影响正在增加。根据阿尔茨海默氏症协会的数据，英国有超过 85 万人患有痴呆症，2013 年给英国造成 260 亿英镑的损失。因此，对这些疾病的治疗研究至关重要。对脑内皮糖萼（CeGC）的研究可能提供有效的治疗方法。CeGC 由糖蛋白聚糖、糖蛋白和糖脂组成，是一种覆盖全身毛细血管内皮细胞腔侧的动态结构。CeGC 在脑微血管中更厚，表明其作为血脑屏障（BBB）一部分的功能专门化。最近的研究证据表明，CeGC 对于保护脆弱的实质组织和 BBB 的有效功能至关重要，因为 CeGC 的一个特别重要的功能是作为保护屏障和通透性调节剂。CeGC 的降解是导致 BBB 通透性增加的因素之一。它在衰老过程中自然发生，但在与认知障碍相关的多种情况下已经证明了过早降解，如炎症、脑水肿、脑疟疾、阿尔茨海默病和最近的新冠病毒。对 CeGC 损伤机制的不断深入研究导致了预防技术的研究，表明 CeGC 可能是一种诊断标志物和治疗靶点。然而，证据相对较新，不一致，主要在实验模型中得到证实。这篇综述评估了 CeGC 的当前知识，包括其结构、功能、损伤和修复机制，以及其退化对多种疾病认知障碍的影响，强调 CeGC 作为一种可能的诊断标志物和治疗靶点的潜力。
