CAREER: Trauma-Induced Alteration of Vascular Smooth Muscle Mechanics

点击翻译按钮获取中文摘要

Blast-induced traumatic brain injury (bTBI) can occur following exposure to the blast wave from a nearby explosion even in the absence of visible injury. A common consequence of brain injury is a spasm in the small muscles surrounding the arteries of the brain that cuts off circulation. Cerebral vasospasm is more common after a blast injury than after a blunt force brain injury. Recent results suggest that when a blast wave enters the body it travels preferentially through the arteries, stretching and injuring the small muscles and causing the spasm. This Faculty Early Career Development (CAREER) Program award supports fundamental research aimed at understanding how traumatic forces, like those in bTBI, alter the properties and behavior of vascular smooth muscle cells. The result will be a better understanding of the mechanisms involved in bTBI injury, providing insight for potential therapeutic approaches. Our recent findings suggest that large high-strain-rate stresses in cerebral VSMCs during a blast can initiate hypercontractility and phenotype switching, both of which are indicative of vasospasm onset, and are likely to alter the mechanical properties of the cells. We hypothesize that: (1) cerebral vasospasm can be initiated when stress in vascular smooth muscle cells exceeds some threshold value during blast injury; and (2) hypercontractility and phenotype switching caused by blast injury induce changes in vascular smooth muscle cell mechanical properties that result in greater cell stresses during subsequent blasts, increasing the likelihood of further injury. Here, we will develop novel methods for measuring the anisotropic and nonlinear strain energy density function and quasilinear viscoelastic properties of individual cells to determine the stress in VSMCs during blast injury. We will then apply blast-like high-velocity stretching to VSMCs and measure the changes in contractility, phenotype, and mechanical properties to determine how vasospasm onset influences vascular cell stress during subsequent injuries.