The glycocalyx: a potential contributor to post-stroke complications

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.