ERI: Toward Unfolding the Effect of Sex Variations in Biomechanics of Traumatic Brain Injury

Traumatic brain injury (TBI) and many other brain diseases/injuries exhibit sex differences in prevalence. onset. and outcomes. Some of these differences are attributed to the fact that the human brain is sexually dimorphic and there are certain regional and structural differences that exist between male and female brains. However. the effect of these sex variations in biomechanical responses of brain have not been elucidated. The paucity of sex-specific knowledge in brain biomechanics and TBI fields is mainly due to the fact that. these fields have predominantly focused on males. there is no sex-specific brain template currently available. and all brain finite element computational models (FEMs) used to establish TBI risk assessment tools and design safety devices are based on average adult male brain. and thus their outcomes. findings. and effectiveness are biased towards males. As a female researcher in the field of TBI and brain computational modeling. the PI realizes the importance. feels the responsibility for. and aims at unfolding the factors contributing to sex variations in brain biomechanics of TBI. The central premise of this proposal is that the sex variations in the human brain structure can be characterized and computationally modeled and their effects on brain injury susceptibility and outcomes can be quantified. The scientific aims are to: (1) identify and characterize the structural sex variations in the regional and overall brain volume. surface area. cortical thickness and shape. structural white matter tracts connectome. etc. that affect biomechanical tissue response and for the first time create detailed average adult female and male brain templates from biomechanics perspective using a set of magnetic resonance imaging data; (2) Investigate the effect of these sex-specific brain variations in injury susceptibility. occurrence. location. and pattern in females and males by developing sex-specific brain FEMs incorporating the sex variations identified in aim1 and multi-scale FEM techniques and using them to simulate common TBI-induced head exposures. The outcomes of this work can also lead to identification of factors that predispose females to more severe TBI and recommendations for design of sex-specific safety equipment.