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Via computational modeling, we elucidate how perturbations in physical properties of the salient components of axonal cytoskeleton impact the intraaxonal load-bearing mechanism, potentially resulting in its failure. Immunohistochemical analyses of tissue from an in vivo model of TBI confirm the presence of cytoskeletal neurochemical degradation. In conjunction with the experiments, our model explains the clinical observation of exacerbated axonal pathology after repetitive TBIs. 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