Animal models of closed-skull, repetitive mild traumatic brain injury

The underlying mechanisms that result in neurophysiological changes and cognitive sequelae in the context of repetitive mild traumatic brain injury (rmTBl) remain poorly understood. Animal models provide a unique opportunity to examine cellular and molecular responses using histological assessment, which can give important insights on the neurophysiological changes associated with the evolution of brain injury. To better understand the potential cumulative effects of multiple concussions, the focus of animal models is shifting from single to repetitive head impacts. With a growing body of literature on this subject, a review and discussion of current findings is valuable to better understand the neuropathology associated with rmTBl, to evaluate the current state of the field, and to guide future research efforts. Despite variability in experimental settings, existing animal models of rmTBl have contributed to our understanding of the underlying mechanisms following repeat concussion. However, how to reconcile the various impact methods remains one of the major challenges in the field today. (C) 2019 Elsevier Inc. All rights reserved.