Exploring the beneficial effects of cardiorespiratory fitness and exercise on cerebrovascular health in Huntington's Disease : a cross-species approach

• Main Author: Furby, Hannah
• Published: Cardiff University 2016
• Subjects: 616.85; BF Psychology
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.716013

This thesis explores the benefits of physical activity on cerebrovascular health in healthy subjects and in Huntington’s Disease (HD), where cerebrovascular health is thought to be jeopardised. A cross-species approach was employed, to inform the relevance of MRI findings in humans, using histology and pre-clinical imaging. In Chapter 2, measurement of cerebrovascular markers using arterial spin labelling (ASL) MRI showed that arterial compliance and resting cerebral blood flow was lower in subjects with higher cardiorespiratory fitness, whilst differences in cerebrovascular reactivity (CVR) to a breath-hold task were not statistically significant. Measurements of vessel density in Chapter 3 showed that running mice had greater vessel density than non-running mice following a 6-week voluntary wheel running intervention, which may be attributed to a process of angiogenesis. Methods developed in healthy subjects were subsequently applied to investigate the cerebrovascular benefits of exercise in HD. In Chapter 4, pre-/early- symptomatic patients with HD were assessed for subtle differences in cerebrovascular health and whether this varied with cardiorespiratory fitness. Disease-related differences were observed in cognition, and ASL measures including resting CBF and CVR, but no clear relationship with fitness was observed. Preclinical imaging was used in Chapter 5 to measure longitudinal changes in resting CBF and CVR in a transgenic Q175 mouse model of HD, prior to behavioural deficits (preHD). Neither CBF or vessel density differed between preHD animals and controls, and did not appear altered by voluntary running.