Biomechanical insights into traumatic brain injury in Females: Current understanding and future directions

The incidence of traumatic brain injury (TBI) in females has increased in recent decades, driven by socioeconomic changes and greater participation in high-risk activities. This rise, combined with the historically limited availability of experimental data from female subjects, highlights the pressing need to improve both the quantity and quality of sex-specific data. Research has identified systematic differences between males and females in brain volume, tissue stiffness, and gray/white matter composition. While differences in brain size are often linked to body dimensions, sex-specific disparities in biomechanical properties, such as viscoelasticity and regional stiffness, may influence TBI susceptibility. Imaging-based techniques, particularly Magnetic Resonance Elastography (MRE), have revealed that female brains tend to exhibit higher stiffness in regions like the occipital and temporal lobes, suggesting a differential biomechanical response to TBI. These regional differences may also serve as potential biomarkers for the diagnosis, monitoring, and tracking the progression of neurodegenerative diseases such as multiple sclerosis, aiding in the assessment of disease progression and therapeutic response. Despite these insights, most current finite element head models (FEHMs) rely on population-averaged parameters that may not adequately represent female-specific tissue mechanics. This review highlights the need to incorporate sex-specific mechanical properties into numerical simulations to improve the accuracy of TBI risk assessments and injury prediction. We emphasize the need for future studies using imaging, experimental methods, and computational modeling to better understand the biomechanical behavior of female brain tissue. Such efforts are essential for advancing personalized approaches to brain injury prevention, diagnosis, and treatment in females.