The Response of Brain Cells to Traumatic Injury

创伤性脑损伤是一种多样而复杂的损伤，每年影响170万美国人。幸存者经常会有永久性的认知丧失、行为问题和情绪障碍，这些都会影响他们的一生。这些改变生活的变化很可能是由于大脑细胞受到损伤引起的。目前尚不清楚的是，脑细胞的行为是如何受到损伤期间发生的事件的影响的。为了探索脑细胞对创伤性脑损伤的反应，研究小组开发了一种新型的台式碰撞试验机。与汽车行业使用的全尺寸碰撞测试系统的概念类似，台式系统将用于对实验室培养的脑细胞群体施加冲击条件。从这项研究项目中获得的知识可以帮助阐明创伤性脑损伤后鲜为人知的细胞变化，并帮助指导新疗法的发展。该项目将对神经科学、生物医学工程和医疗保健领域产生更广泛的影响。这项研究将由旨在激励科学参与的本科和高中学术水平的综合教育项目加以补充。星形胶质细胞是一种普遍存在于脑组织中的细胞，在神经元存活中起着重要作用。然而，星形胶质细胞的机械生物学，特别是它们的神经支持作用是如何受到创伤性脑损伤过程中产生的机械刺激的影响的，还没有得到很好的理解。本研究将探索星形胶质细胞的机械生物学，并探讨脑外伤后星形胶质细胞产生的神经退行性细胞外基质环境是由机械刺激引发的假说。为了探索这一假设，研究团队将采用定制的冲击生物反应器和细胞培养系统来(1)精确地将创伤性脑损伤模拟冲击应用于培养的星形胶质细胞群体；(2)浓缩并收集响应冲击负荷而释放的可溶性（生长因子和细胞因子）和不可溶性（细胞外基质）分子。更好地理解冲击刺激与可溶性和不可溶性分子产生之间的关系，将有助于阐明星形胶质细胞在创伤性脑损伤后神经变性过程中的作用。

Traumatic brain injury is a diverse and complex injury that affects 1.7 million Americans annually. Survivors frequently have permanent cognitive loss, behavioral issues, and emotional disturbances that affect them throughout their life. These life-altering changes are likely caused by damage to the cells of the brain that occur in response to injury. What remains unclear is how the behavior of brain cells is influenced by the events that occur during injury. To explore the response of brain cells to traumatic brain injury the research team has developed a novel bench top crash tester. Similar in concept to the full scale crash test systems used by the automotive industry, the bench top system will be used to apply impact conditions to populations of brain cells grown in the lab. The knowledge gained from this research program could help illuminate the poorly understood cellular changes that follow traumatic brain injuries and help guide the development of new therapies. The project will have broader impacts on neuroscience, biomedical engineering, and the healthcare field. The research will be complemented by integrated educational projects at the undergraduate and high school academic levels that are designed to motivate scientific participation.Astrocytes are ubiquitous cells throughout brain tissue that play an essential role in neuronal survival. Yet, the mechanobiology of astrocytes, and in particular how their neuro-supportive role is affected by the mechanical stimuli that are generated during traumatic brain injury is not well understood. This research program will explore the mechanobiology of astrocytes, and investigate the hypothesis that the neuro-degenerative extracellular matrix environment produced by astrocytes following traumatic brain injury is triggered by mechanical stimuli. To explore this hypothesis, the research team will employ a custom impact bioreactor and cell culture system to (1) precisely apply traumatic brain injury mimetic impacts to populations of astrocytes in culture and (2) concentrate and collect the soluble (growth factors and cytokines) and insoluble (extracellular matrix) molecules released in response to impact loading. An improved understanding of the relationship between impact stimuli and the production of soluble and insoluble molecules will help elucidate the role astrocytes play in the neuro-degeneration processes that follow traumatic brain injury.