Animal models of traumatic brain injury: a review of pathophysiology to biomarkers and treatments.

Traumatic brain injury (TBI) is one of the main causes of death and disability in both civilian and military population. TBI may occur via a variety of etiologies, all of which involve trauma to the head. However, the neuroprotective drugs which were found to be very effective in animal TBI models failed in phase II or phase III clinical trials, emphasizing a compelling need to review the current status of animal TBI models and therapeutic strategies. No single animal model can adequately mimic all aspects of human TBI owing to the heterogeneity of clinical TBI. However, due to the ethical limitations, it is difficult to precisely emulate the TBI mechanisms that occur in humans. Therefore, many animal models with varying severity and mechanisms of brain injury have been developed, and each model has its own pros and cons in its implementation for TBI research. These challenges pose a need for study of continued TBI mechanisms, brain injury severity, duration, treatment strategies, and optimization of animal models across the neurotrauma research community. The aim of this review is to discuss (1) causes of TBI, (2) its prevalence in military and civilian population, (3) classification and pathophysiology of TBI, (4) biomarkers and detection methods, (5) animal models of TBI, and (6) the advantages and disadvantages of each model and the species used, as well as possible treatments.