Traumatic brain injury (TBI) occurs in many blunt, ballistic and blast impact events. During trauma axons in the white matter are especially vulnerable to injury due to the rapid mechanical loading of brain. The axonal pathology leads to cytoskeletal failure and disconnection. The microtubules are one of major structural components of the cytoskeleton filamentous network. By bridging the macroscopic forces acting on the whole brain with the cellular and subcellular failure, the macro-micro computational models in both time and space can help us better understand the complex biophysics and elucidate the injury mechanism of both severe and mild TBI (concussion). At the macroscopic scale we developed the high-fidelity anatomical human body finite element model (FEM) to predict intracranial pressures and strain and strain rate fields of brain in the blast event. The macro-scale models and the coupled blast and biomechanics approach were validated against test data of shock wave interacting with a surrogate head in the shock tube. The mechanical deformation of brain tissue was mapped to the white matter tracts to obtain local axonal strain and strain rate for the micromechanical models. We developed the micromechanical FEM of myelinated axons interconnected with the oligodendrocyte by the processes, utilizing a novel beam element free of rotational degrees of freedom (DOFs). The numerical results reveal the possible mechanism of impact-induced axon injury including demyelination, breakup of processes, and axonal varicosity. We also investigate the dynamic response of microtubules bundles under traumatic loading. Different from the commonly discrete bead-spring models, a network of microtubules cross-linked with microtubule-associated-protein (MAP) tau proteins was modeled by the nonlinear beam model. Tau protein is modeled by the rate-dependent bar element for its complicated material behavior. The model considers the rupture of microtubule and the failure of tau-tau interface and tau-microtubule interface. The simulation result of the combined effects of the failure of the cross-linked architecture and elongation and bending of the bundle are possibly correlated to the axonal undulations following traumatic loading observed in the experiments. The developed macro-micro biomechanics models can be used as a starting point for modeling the neurobiology effects and guide the design of novel injury protection strategies.

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