TBI-induced vessel softening increases brain susceptibility to injury with repeated head trauma

Repeated traumatic brain injury (TBI) is a significant concern among military personnel, athletes, and abuse victims. However, little is known about the mechanisms that drive the brain's apparent increase in injury susceptibility with repeated loading. One critical factor may be the softening of cerebral blood vessels, which are significantly stiffer than brain tissue and influence its mechanical response during trauma. In this study, we employed a finite element model of a Göttingen minipig head to investigate how progressive vascular softening influences strain changes in brain tissue during both repeated blast and rapid rotation. The model incorporated pig-specific anatomical detail and material properties, including detailed cerebral vasculature. Simulations included six repeated exposures of either blast overpressure or coronal or sagittal rotations at varying severity levels. Additional "no-vasculature" (NV) cases were included for each loading condition to benchmark the mechanical contribution of blood vessels. Vessel softening was applied after each exposure based on previous experiments on Göttingen minipig cerebral arteries. While blast exposures did not generate sufficient strain to induce vessel softening, rotational events led to progressively increasing brain strain with repetition, especially in regions adjacent to softened vessels. These increases progressed toward the NV condition with repetition, consistent with diminishing structural support by softened vessels. Results also showed increasing risk of vessel rupture and axonal injury with repetition. These findings elucidate the biomechanical role of vessel softening in repeated TBI and suggest that even sub-failure vessel damage may exacerbate brain strain in repeated exposures and elevate injury risk.