Microstructural damage progression in the pia-arachnoid complex.

Abstract

Traumatic brain injury is a leading cause of death and disability worldwide, with mild traumatic brain injury comprising the majority of cases. The pia-arachnoid complex (PAC), located at the brain-skull interface, plays a critical role in brain mechanics during head impacts, yet its response to mechanical loading is understudied. This study investigates the progression of microstructural damage in the PAC under sub-failure cyclic mechanical loading. Using a newly developed inflation technique, we measured the displacement of the arachnoid membrane in piglets, adult pigs, and adult sheep during alternating low-pressure (characterization) and high-pressure (injury) inflation cycles. Optical coherence tomography imaging was combined with direct pressure measurements to quantify changes in stiffness. Results showed that tensile loading caused significant softening of the PAC, with damage correlating to the severity of deformation. Damage progressed with subsequent tensile loading cycles, showing an exponentially decreasing trend with strain severity. While some recovery was observed after a rest period, the mechanical changes were permanent and not attributed to viscoelasticity. Furthermore, the mechanics of the PAC was significantly affected by age (p < 0.0003), with piglets displaying higher stiffness compared to adult pigs. There were no statistically significant species effects. These findings represent a first step in understanding the damage and damage progression of the PAC under sub-failure mechanical loading, advancing our understanding of how repetitive head trauma contributes to increasing risk of brain injury. STATEMENT OF SIGNIFICANCE: Traumatic brain injury (TBI) remains a major public health issue, yet the biomechanical processes driving damage in repetitive head trauma-especially at the brain-skull interface-are not well understood. This study quantifies damage and damage progression to the pia-arachnoid complex (PAC) under sub-failure cyclic loading using a custom inflation system, optical coherence tomography, and direct pressure measurements. By tracking arachnoid membrane displacement in piglets, adult pigs, and adult sheep, we quantified changes in PAC stiffness over multiple loading cycles and observed progressive softening that correlated with strain severity and was largely irreversible. These findings uncover a potential mechanism of damage accumulation at the brain-skull interface, offering critical insights for modeling repetitive TBI and informing future prevention strategies.