The controlled cortical impact (CCI) model has been extensively used to study region-specific patterns of neuronal injury and cell death after a focal traumatic brain injury. Although external parameters such as impact velocity and depth of penetration have been defined in this injury model, little is known about the intracranial mechanical responses within cortical and subcortical brain regions where neuronal loss is prevalent. At present, one of the best methods to determine the internal responses of the brain is finite element (FE) modeling. A previously developed and biomechanically validated detailed three-dimensional FE rat brain model, consisting of 255,700 hexahedral elements and representing all essential anatomical features of a rat brain, was used to study intracranial responses in a series of CCI experiments in which injury severity ranged from mild to severe. A linear relationship was found between the percentage of the neuronal loss observed in vivo and the FE model-predicted maximum principal strain (R(2) = 0.602). Interestingly, the FE model also predicted some risk of injury in the cerebellum, located remote from the point of impact, with a 25% neuronal loss for the "severe" impact condition. More research is needed to examine other regions that do not have histological data for comparison with FE model predictions before this injury mechanism and the associated injury threshold can be fully established.