Sex Differences in Axonal Dynamic Responses Under Realistic Tension Using Finite Element Models

Area of Science:

• Biomechanics
• Neuroscience
• Computational Modeling

Background:

• Existing axonal finite element models lack sex-specific morphology and dynamic input fidelity.
• Understanding diffuse axonal injury (DAI) requires detailed micromechanical insights.
• Sex-based differences in brain injury outcomes necessitate sex-specific modeling approaches.

Purpose of the Study:

• To develop a parameterized modeling approach for generating sex-specific axonal models.
• To investigate the role of microtubule (MT) gaps and dynamic loading on axonal injury.
• To compare the micromechanical responses of female and male axons under simulated head impact.

Main Methods:

• Generated sex-specific axonal models with random microtubule gap configurations.
• Simulated realistic tensile loading including loading and recovery phases from head impact data.
• Employed a statistical approach with 10,000 models each for female and male axons to analyze responses.

Main Results:

• Microtubule gaps and the dynamic recovery phase are critical for reproducing experimentally observed MT undulation.
• Female axons exhibited substantially higher peak strains in microtubules and at the Ranvier node compared to male axons.
• Associated neurofilament failures were significantly greater in female axons due to fewer MTs and random gap distribution.

Conclusions:

• The study highlights the importance of characterizing MT gap configurations and realistic dynamic inputs for axonal simulations.
• Findings suggest a biomechanical basis for sex differences in brain injury, with female axons being more vulnerable.
• The developed modeling approach provides a foundation for future microscale investigations into axonal injury.