Traumatic axonal injury (TAI) contributes to the mortality and morbidity following diffuse traumatic brain injury (TBI). Previous work has shown that following TBI, alterations in the molecular domains of axons result in TAI. It is currently posited that injury induced ionic flux is responsible for activating deleterious proteolytic cascades, resulting in altered distributions of axonal components. However, the underlying mechanism of this progressive pathology remains elusive. This study further explores the hypothesis that altered molecular domains contributes to the progressive intra-axonal changes that characterize TAI. Using a rodent model of impact acceleration TBI we examined the expression of nodal and paranodal domains of myelinated axons in brainstem over a 24 h period post-injury. Western blot analysis was utilized to quantify changes in protein levels of Nav1.6, a prominent component at the node of Ranvier, and Caspr, a constituent of the paranodal tripartite complex. Here we report that diffuse TBI causes an up-regulation of Nav1.6 and a down-regulation of Caspr over a 24 h time-course post-injury. The results of this study support that alterations in the molecular components of the domains of injured axons contribute to the cellular mechanism of TAI and thus provides novel data in the field of TBI research.