CAREER: Trauma-Induced Alteration of Vascular Smooth Muscle Mechanics

职业：创伤引起的血管平滑肌力学改变

• 批准号: 1553255
• 负责人: Patrick Alford
• 金额: $ 50万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1553255&HistoricalAwards=false
• 关键词: CAREER; Trauma; Induced; Alteration; Vascular

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.

即使没有明显的损伤，暴露于附近爆炸产生的冲击波后也可能发生爆炸引起的创伤性脑损伤 (bTBI)。 脑损伤的一个常见后果是大脑动脉周围的小肌肉痉挛，从而切断血液循环。爆炸伤后脑血管痉挛比钝性脑损伤后更常见。最近的研究结果表明，当冲击波进入体内时，它会优先通过动脉传播，拉伸和损伤小肌肉并引起痉挛。该学院早期职业发展 (CAREER) 计划奖项支持旨在了解创伤性力量（如 bTBI 中的创伤性力量）如何改变血管平滑肌细胞的特性和行为的基础研究。其结果将是更好地了解 bTBI 损伤的机制，为潜在的治疗方法提供见解。我们最近的研究结果表明，爆炸期间脑 VSMC 中的大高应变率应力可以引发过度收缩和表型转换，这两者都表明血管痉挛的发生，并且可能改变细胞的机械特性。我们假设：（1）冲击波损伤时，血管平滑肌细胞的应激超过某个阈值，就会引发脑血管痉挛； （2）爆炸损伤引起的过度收缩和表型转换会引起血管平滑肌细胞机械特性的变化，导致随后的爆炸期间细胞应力更大，增加进一步损伤的可能性。在这里，我们将开发测量单个细胞的各向异性和非线性应变能密度函数和准线性粘弹性特性的新方法，以确定爆炸损伤期间 VSMC 的应力。然后，我们将对 VSMC 应用爆炸式高速拉伸，并测量收缩性、表型和机械特性的变化，以确定血管痉挛发作如何影响后续损伤期间的血管细胞应激。