Computational and experimental approaches to quantify the influence of pathlogical hemodynamics on hippocampal astrocyte dysfunction
Date
2025
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Alzheimer’s disease (AD) and vascular dementia (VD) are major causes of disability and death in people over 65. While the cellular and molecular mechanisms that govern the initiation and progression of AD/VD are not fully understood, evidence suggests that changes in mechanical cues including high blood pressure, age-related arterial stiffening, and age-related brain softening are likely contributors. Arterial stiffening of elastic blood-vessels is thought to change normal blood flow patterns, thus resulting in neuronal inflammation and injury via mechanical strain-mediated mechanisms. Therefore, I hypothesize that exposure to pathological changes in elasticity, in both the µvessel wall and brain tissue, and high magnitude blood pressure exacerbates and astrocyte injury due to increased mechanical strain transmission to the surrounding tissue. Here, I propose investigating my hypothesis through the following means: (1) Develop methodology for characterizing micromechanical properties of hydrogels via microindentation. (2) Develop a predictive computational model of brain-tissue strain as a function of pressure and tissue elasticity. (3) Develop an in vitro microfluidic model to control pulse pressure to determine its influence on hippocampal astrocyte behavior.
Description
Keywords
Astrocyte, Finite element model, Microfluidic model, Strain