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

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.