Short-term behavioral and histological changes in a rodent model of mild traumatic brain injury

Abstract

An in-house developed weight drop injury (WDI) device is a recently described animal model of traumatic brain injury (TBI) that was designed to produce a blunt, closed-head injury. More specifically, the apparatus was designed to reliably generate a wide range of TBI severities using precise and quantifiable biomechanical inputs in a nonsurgical user-friendly platform. The objective of this study was to define the lower limit of a single mild TBI (mTBI) impact using our WDI device by characterizing the relationship between the biomechanical input and the behavioral and histological inflammatory outcomes. Rats were subjected to a single mTBI impact using two impact energies of 0.2 and 0.5J, and post-impact outcomes were assessed over two recovery periods of 3- and 7-days. Here we report that a single, closed-head impact energy of 0.5J and below produces no significant phenotype. Despite the insignificant results of alterations in behavior and inflammatory analysis, the study revealed important aspects of lower-level impact loads. First, this work provides evidence in support of the notion that not every closed-head impact has the capacity to result in system perturbations. Although a theoretical injury threshold may not exist for rats using a WDI model, we hypothesize a biomechanical threshold of impact associated with a lack of functional impairment and neuroinflammation due to a single closed-head injury is likely around an energy level of 0.5 J.