Animal models are essential to gain a deeper understanding of the pathophysiology associated with traumatic brain injury (TBI). Rodent models of TBI have proven highly valuable with respect to the information they have provided over the years, particularly when it comes to the molecular understanding of injury mechanisms. However, there has been a failure to translate the successes in therapeutic treatment of TBI in rodents, which many believe may be related to their different brain anatomy compared with humans. Specifically, the rodent lissencephalic brain within its bony skull responds differently to injury than a human gyrencephalic brain, particularly from a biomechanical and physiological perspective. There is now far greater interest in developing more clinically relevant, large animal models of TBI so as to enhance the possibility of successful clinical translation.The current mini-review highlights the differences between lissencephalic and gyrencephalic brains, emphasizing how these differences might impact studies of TBI. Thereafter follows a summary of the different large animal models, with a critical analysis of their strengths and weaknesses.
| I N TR ODU C TI ONIt is widely accepted that an understanding of the pathology associated with human traumatic brain injury (TBI) and the development of effective treatment strategies cannot be optimally pursued in a clinical scenario. Indeed, the heterogeneity of injury in clinical TBI is simply too complex to identify independent mechanisms of injury, largely because the primary injury in human TBI is caused in a variety of ways ranging from direct impact of the head to acceleration/deceleration and blast (Gennarelli, 1993). Moreover, this primary mechanical injury initiates a secondary injury cascade that is in large part dependent on the type of primary insult (Blumbergs, Reilly, & Vink, 2008). For example, penetrating focal injuries result in extensive hemorrhage that is not typical of acceleration/deceleration injuries, with this hemorrhage and external access to the brain presenting an entirely different secondary injury cascade with its own peculiar challenges compared with more diffuse injury. Accordingly, experimental models of TBI have been developed to replicate specific aspects of the human condition such that the different factors associated with injury can be individually identified and appropriate targeted interventions developed (Cernak, 2005). And while most models do not replicate all aspects of the human condition, this is a necessary prerequisite given that human injury reflects a complex spectrum of different injury mechanisms. Different animal models allow the differentiation of these injury mechanisms. Only after the differentiation of these neuronal injury mechanisms has been successfully achieved can the complicating effects of extracranial injury, hemorrhagic shock, and clinically realistic treatment and resuscitation strategies be examined in detail.Of the variety of animal species currently being used to model TBI, the r...