The glycocalyx: a potential contributor to post-stroke complications

中风仍然是世界范围内死亡和残疾的主要原因，治疗选择有限。除了中风的直接和常见的症状，如四肢无力和语言问题，中风患者经常会出现并发症。这些并发症包括迅速发展的感染，或者随着时间的推移而发展的感染，包括焦虑、抑郁、疲劳和记忆障碍。这些问题对中风后的康复和生活质量产生了负面影响。大多数中风患者都是老年人和/或有共同发病(如最近的感染、高血压、糖尿病或肥胖)；可能影响预后和康复的条件或危险因素。我们之前的工作试图通过包括共病来更好地模拟典型的中风患者，并表明在存在肥胖等共病的情况下，实验性中风后的结果更差。中风反应的一个重要因素是脑血管的健康状况。大多数中风的危险因素会导致血管系统的紊乱，从而影响结构和功能。因此，了解中风后血管系统的变化是成功靶向导致更糟糕结果的机制的关键。血管系统中一个未被重视的成分是糖萼。糖萼是由蛋白多糖、糖胺多糖链和糖蛋白组成的一层，覆盖在血管内皮细胞的管腔表面，在维持血管健康方面具有重要作用。糖萼的功能包括限制血管通透性、白细胞黏附和微血管血栓形成以及控制微血管张力。在高血压、糖尿病和肥胖症中可以看到糖萼厚度的减少。在中风患者中，糖萼也变薄，并观察到其在血浆中的可溶性成分增加，这表明脱氧酶活性和糖萼损伤。此外，脓毒症后的认知障碍被认为是由糖萼脱落所介导的。因此，我们假设卒中后脑血管中的糖唇脱落可能会损害血管功能并恶化预后。具体地说，学生将使用中风的实验模型来测试糖基化是否会导致/增加中风后的短期和长期(记忆障碍、焦虑、抑郁和疲劳)并发症。学生还将确定肥胖共病的影响。最后，学生将测试是否可以在中风患者的血液中检测到糖粘蛋白的分解产物，以及它们是否与患中风后长期并发症(包括记忆力下降、抑郁和疲劳)的风险更高有关。这项研究将提供重要的数据，表明糖基化是否会影响卒中后并发症的风险，这可能会为卒中后改善康复的治疗干预提供一种新的途径。

Stroke remains a leading cause of death and disability worldwide with limited treatment options. In addition to the immediate and common symptoms of stroke such as limb weakness and speech problems, stroke patients often develop complications. These complications include infection, which can develop quickly, or those that develop over time including anxiety, depression, fatigue, and memory impairment. These problems have a negative impact on recovery and quality of life after stroke. Most stroke patients are elderly and/or present with co-morbidity (such as recent infection, hypertension, diabetes or obesity); conditions or risk factors that can affect outcome and recovery. Our previous work has tried to better model a typical stroke patient by including co-morbidity and has shown that outcome after experimental stroke is worse in the presence of co-morbidities like obesity. An important factor in the response to stroke is the health of the cerebrovasculature. Most risk factors for stroke cause a perturbation in the vascular system that affects structure and function. Understanding the changes in vasculature after stroke is therefore key to successful targeting of mechanisms that lead to worse outcome. One unappreciated component of the vasculature is the glycocalyx. The glycocalyx is a layer comprised of proteoglycans, glycosaminoglycan chains, and glycoproteins that covers the luminal surface of endothelial cells and has an important role in maintaining vascular health. Functions of the glycocalyx include limiting vascular permeability, leukocyte adhesion and microvascular thrombosis and control of microvascular tone. Reduced glycocalyx thickness is seen in hypertension, diabetes and obesity. In stroke patients the glycocalyx is also thinner and an increase in its soluble components in the plasma have been observed, suggesting sheddase activity and glycocalyx damage. Furthermore, cognitive impairment after sepsis is thought to be mediated by glycocalyx shedding. Thus, we hypothesise that glycocalyx shedding in the cerebrovasculature after stroke could impair vascular function and worsen outcome. Specifically, the student will use an experimental model of stroke to test if glycocalyx breakdown causes/increases short-term and long-term (memory impairment, anxiety, depression and fatigue) complications after stroke. The student will also determine the impact of the co-morbidity obesity. Finally, the student will test if breakdown products of the glycoclayx can be detected in the blood of stroke patients and if they are linked to a higher risk of development of longer-term post-stoke complications including memory decline, depression and fatigue. This study will provide essential data indicating whether glycocalyx breakdown affects the risk of post-stroke complications, and this may lead to a new avenue for therapeutic intervention to improve recovery after stroke.