Investigating the Impact of Load-Dependent and Structural Arterial Stiffness on Cerebrovascular Blood Flow in Individuals Post-Stroke

PROJECT SUMMARY/ABSTRACT Individuals post-stroke exhibit significantly increased total arterial stiffness and reduced cerebral blood flow compared to healthy age- and sex-matched peers. Increased total arterial stiffness and reduced cerebral blood flow place individuals post-stroke at an elevated risk for recurrent stroke and cerebrovascular decline. An emerging body of literature suggests that investigating the mechanisms which underly total arterial stiffness, namely load-dependent and structural arterial stiffness, provides increased insight into how arterial stiffness impacts cerebrovascular decline. However, there remains a clear lack of knowledge regarding how load- dependent and structural arterial stiffness affect cerebrovascular blood flow in individuals post-stroke. A critical need exists to evaluate the impact of structural and load-dependent stiffness on cerebrovascular blood flow post-stroke, to allow for future interventions to be developed targeting a reduction in arterial stiffness and the related cerebrovascular decline. The objective of this proposal is to determine the distinct impacts of load- dependent and structural arterial stiffness on cerebrovascular blood flow at rest, and during a dynamic sit-to- stand task, in individuals with stroke. For Aim 1, I hypothesize that structural arterial stiffness will be inversely associated with resting cerebral blood flow, and load-dependent stiffness will be inversely associated with resting cerebrovascular conductance, or the ease at which blood travels through arteries. For Aim 2, I hypothesize that load-dependent arterial stiffness will be inversely associated with cerebrovascular conductance during a dynamic sit-to-stand task, and structural arterial stiffness will be inversely related to change in brain blood flow amplitude when transitioning from sitting to standing. To test these hypotheses, I will leverage existing data collected from an ongoing clinical trial in individuals with stroke. I will calculate carotid and aortic load-dependent and structural arterial stiffness using common carotid ultrasound recordings, carotid-femoral pulse wave velocity data, and established mathematical modeling. I will use middle cerebral artery blood flow velocity data, collected using transcranial doppler ultrasound at rest and during a dynamic sit- to-stand task, to evaluate cerebral blood flow and cerebrovascular conductance. Collectively, these data will demonstrate how load-dependent and structural arterial stiffness influence resting and dynamic cerebrovascular blood flow in individuals with stroke. This proposed work will have broad implications for arterial stiffness and cerebrovascular health post-stroke, contributing to the development of future interventions which seek to improve arterial stiffness and cerebrovascular health in individuals with stroke.