Large animal models of traumatic brain injury

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.