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

EAGER：脑震荡中的短暂脑脊液 (CSF) 流动

• 批准号: 2322067
• 负责人: Qianhong Wu
• 金额: $ 29.79万
• 依托单位: Villanova University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2322067&HistoricalAwards=false
• 关键词: EAGER; Transient; Cerebrospinal; Fluid; CSF

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.

对头部的撞击被艾德为脑震荡损伤的常见原因。据估计，美国每年有280万人遭受创伤性脑损伤（TBI），占所有与损伤相关的死亡的30.5%，每年的费用估计为600亿美元。为了制定有效的预防和干预策略，关键是要了解脑脊液（CSF）-沐浴的大脑如何应对突然的外部冲击，以及什么机械和细胞机制驱动脑震荡损伤的病理发展。然而，由于大脑的令人生畏的复杂性，颅骨和大脑之间的蛛网膜下腔（SAS）的小范围，极其短暂的特征，以及颅骨的不透明性，阻止直接可视化CSF流和顺应性大脑之间的任何复杂的物理相互作用，脑震荡的机制仍然不清楚。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，以首次揭示脑震荡期间瞬时CSF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，其潜力可以指导创建有效的头部保护，减少脑震荡的发生率，节省大量成本，并通过挽救生命造福社会。该项目还将包括重要的教育活动，包括课程改革，多年本科研究计划，以及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代表性不足的少数民族高中学院的外联方案。该项目的目标是检查当头部暴露于快速外部冲击时充满蛛网膜小梁（AT）的多孔蛛网膜下腔（SAS）中的瞬态脑脊液流动，从而阐明CSF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。分析和数值模型，捕捉关键的CSF流动物理，已被忽视的日期，将使用一种新的仿生实验平台进行测试，并进一步评估体内生物力学研究。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。该奖项反映了NSF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。