(MRC DTP) Zinc deficiency: 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, or obesity); conditions 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. Zinc deficiency (low zinc) is another common but poorly understood co-morbidity in stroke patients, which could also affect outcome and recovery. Patients with stroke have reduced levels of zinc in the blood, correlating with more severe strokes and poorer functional status. Zinc deficiency in people without stroke can increase risk of infection and is associated with depression, fatigue and cognitive/memory impairment; the same complications that are often seen in individuals after stroke. Thus it is possible that zinc deficiency negatively influences post-stoke complications. In support, prophylactic administration of zinc prevents memory loss in rats after stroke. Furthermore, we have data showing that zinc deficiency causes an inflammation-dependent worsening of memory in an animal model of Alzheimer’s disease. The overall aim of this PhD project, therefore, is to test the hypothesis that chronic zinc deficiency is a treatable co-morbidity for stroke that causes inappropriate inflammation that increases the risk and/or severity of post-stroke complications. Specifically, the student will use an experimental model of stroke to test if zinc deficiency causes/increases short-term (infection) and long-term (memory impairment, anxiety, depression and fatigue) complications after stroke. The student will then determine if treating with zinc supplementation after stroke can prevent these complications. Finally, the student will test if low levels of zinc in stroke patients are linked to a higher risk of infection and/or the development of longer-term post-stoke complications including memory decline, depression and fatigue. This study will provide essential data indicating whether zinc deficiency affects the risk of post-stroke complications, and this may lead to a clinical trial to test if zinc supplements could be a simple and low-cost treatment to improve recovery after stroke.

https://www.research.manchester.ac.uk/portal/catherine.lawrence.html
https://www.research.manchester.ac.uk/portal/David.Brough.html
https://www.research.manchester.ac.uk/portal/craig.smith-2.html
https://www.research.manchester.ac.uk/portal/stuart.allan.html

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.