19.3 Experimental Models of Traumatic Brain Injury

Traumatic brain injury is very complex at the molecular level since physical trauma is induced by a variety of methods and is influenced by a variety of factors (Albensi, 2001). Although many methods to experimentally model TBI in animals have been created, so far therapeutic interventions have only moderately translated into improved clinical care of human TBI patients (Buki, 2009). This is partially due to the fact that injury heterogeneity is extremely large in the human population due to the variance in force type, patient state at the time of injury, injury location, injury severity and the patient’s environment. On the contrary, animal models seek to replicate injury variables for simplified data analysis and evaluation (Morales, 2005). In animal research, there is often a compromise between creating a model which mimics the complexities of human TBI and creating a model which elicits data that can be accurately quantified and analyzed (Finnie, 2001).

In order for an experimental model of TBI to be valuable, it should encompass several criteria. The mechanical force behind the induction of the injury should be controllable, reproducible, quantifiable, and similar to the mechanisms which induce human TBI (Cernak, 2005; Morales, 2005; Wang & Ma, 2010). The injury produced by the model should mimic certain pathophysiological components of human TBI such that the model is clinically relevant (Cernak, 2005; Finnie, 2001). Animal models of TBI should be able to produce a graded continuum of injury severities (Finnie, 2001; Wang & Ma, 2010). The injury severity and outcome should be associated with the degree of mechanical force which inflicts injury (Cernak, 2005; Morales, 2005). Futhermore, standardized experimental protocols should be available and the injury model should be affordable, simple and widely applicable (Wang & Ma, 2010).

Each experimental model of TBI is suited for a specific scientific objective (Finnie, 2001). Although rodents are the most commonly used animals in experimental models, there is a large discrepancy between rodent and human physiological and behavioural responses to neurotrauma (Cernak, 2005). The anatomical ratio between brain mass and spinal cord is most similar to humans in non-human primates, such that the use of any other animal will always elicit species differences in injury outcomes (Finnie, 2001). The use of larger gyrencephalic animals would be beneficial for this field of research, but budget practicalities and ethical considerations limit the use of larger animals in studies with large sample sizes (Cernak, 2005).

Experimental TBI models are typically divided into focal injuries and diffuse injuries (Buki, 2009). Focal injuries are a direct result of an impact while diffuse injuries are due to the inertial forces present at the time of injury and the acceleration and deceleration of the brain tissue (Buki, 2009). In the majority of human TBI, patients suffer from both focal and diffuse injuries combined.