Multiple length scales are involved in the development of traumatic brain injury, where the global mechanics of the head level are responsible for local physiological impairment of brain cells. In this study, a relation between the mechanical state at the tissue level and the cellular level is established. A model has been developed that is based on pathological observations of local axonal injury. The model contains axons surrounding an obstacle (e.g., a blood vessel or a brain soma). The axons, which are described by an anisotropic fiber-reinforced material model, have several physically different orientations. The results of the simulations reveal axonal strains being higher than the applied maximum principal tissue strain. For anisotropic brain tissue with a relatively stiff inclusion, the relative logarithmic strain increase is above 60%. Furthermore, it is concluded that individual axons oriented away from the main axonal direction at a specific site can be subjected to even higher axonal strains in a stress-driven process, e.g., invoked by inertial forces in the brain. These axons can have a logarithmic strain of about 2.5 times the maximum logarithmic strain of the axons in the main axonal direction over the complete range of loading directions. The results indicate that cellular level heterogeneities have an important influence on the axonal strain, leading to an orientation and location-dependent sensitivity of the tissue to mechanical loads. Therefore, these effects should be accounted for in injury assessments relying on finite element head models.