EAGER: Transient Cerebrospinal Fluid (CSF) Flow in Brain Concussion

对头部的冲击被认为是造成脑震荡的常见原因。据估计，美国每年有280万人遭受创伤性脑损伤（TBI），占所有伤害相关死亡人数的30.5%，每年造成的损失估计为600亿美元。为了制定有效的预防和干预策略，了解脑脊液（CSF）浸泡的大脑如何对突然的外部冲击做出反应以及驱动脑震荡脑损伤病理发展的机械和细胞机制至关重要。然而，由于大脑令人恐惧的复杂性，颅骨和大脑之间的蛛网膜下腔（SAS）的小范围，极短暂的特征，以及颅骨的不透明阻止了脑脊液流与依从性大脑之间任何复杂的物理相互作用的直接可视化，脑震荡的机制尚不清楚。该提案旨在通过将创新的分析，数值和仿生方法与脑震荡动物模型相结合来解决这一具有挑战性的问题，首次揭示脑震荡期间瞬态脑脊液流动的关键作用。该项目将填补一个明显的知识空白，具有高回报的特点，因为它有潜力指导创造有效的头部保护，减少脑震荡的发生率，显著节省成本，并通过挽救生命来造福社会。该项目还将包括重要的教育活动，包括课程改革、多年本科研究项目、年度女童子军日和维拉诺瓦大学（VU）、VU体育部和当地公共图书馆的少数族裔高中学院的外展项目。本项目的目的是研究当头部暴露于快速的外部冲击时，充满蛛网膜小梁（AT）的多孔蛛网膜下腔（SAS）的瞬态脑脊液流动，从而阐明脑脊液流动在传递和减轻外部冲击中的关键作用。该提案整合了分析，数值，实验（仿生和生物力学）调查，建立在坚实和令人鼓舞的初步研究结果之上。分析和数值模型捕获了迄今为止被忽视的关键脑脊液流动物理特性，将使用新型仿生实验平台进行测试，并通过体内生物力学研究进一步评估。这是第一个，也是迄今为止唯一一个试图揭开大脑生物力学长期谜团的研究。预计将产生高度变革性的结果，并为该研究领域的未来研究提供平台。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Impacts to the head are identified as the common cause of concussion injury. An estimated 2.8 million people in the US sustain a traumatic brain injury (TBI) annually which contributes 30.5% of all injury-related deaths and costs an estimated $60 billion annually. To develop effective prevention and intervention strategies, it is critical to understand how the cerebrospinal fluid (CSF)-bathed brain responds to sudden external impacts and what mechanical and cellular mechanisms drive the pathological development of concussive brain injury. However, due to the brain’s forbidding complexity, the small confines of the subarachnoid space (SAS) between the skull and the brain, the extremely transient feature, and the skull’s opacity preventing direct visualization of any complex physical interactions between the CSF flow and the compliant brain, the mechanism of brain concussion remains unclear. The proposal is aimed to tackle this challenging problem by integrating innovative analytical, numerical, and biomimetic approaches with concussion animal models to reveal, for the first time, the crucial roles of transient CSF flow during brain concussion. The project will fill a glaring knowledge gap, with high-payoff feature ensuing from its potentials to guide the creation of effective head protection, reduce the incidence of concussion, lead to significant cost savings, and benefit the society by saving lives. The project will also encompass significant educational activities, including curriculum reform, multi-year undergraduate research program, and outreach programs for Annual Girl Scouts day and High School Academy for Underrepresented Minorities at Villanova University (VU), the VU Athletic Department and the local public libraries. The goal of the project is to examine the transient cerebrospinal fluid flow in the porous subarachnoid space (SAS) filled with arachnoid trabeculae (AT), as the head is exposed to rapid external impacts, and hence to elucidate the critical role of the CSF flow in transmitting and mitigating external impacts. The proposal integrates analytical, numerical, experimental (biomimetic and biomechanical) investigations, built upon solid and encouraging preliminary study results. Analytical and numerical models, capturing the key CSF flow physics that have been neglected to date, will be tested using a novel biomimetic experimental platform, and further evaluated by in vivo biomechanical study. The proposal is the first, and so far, the only study of its kind to attempt to uncover a long-standing mystery in brain biomechanics. It is expected to yield highly transformative results and provide the platform for future study in this research area.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.