Animal Models of Pediatric Traumatic Brain Injury: Lessons Learned
A predominant focus of both clinical and preclinical pediatric traumatic brain injury (TBI) research is to combat secondary injury processes in the acute posttraumatic period that may contribute to pathologies that lead to long-term functional impairments. Identified therapeutic targets must undergo rigorous preclinical testing in relevant animal models of pediatric TBI. Animal models for pediatric TBI use injury mechanisms such as fluid-percussion, rotational-acceleration, weight-drop, and controlled cortical impact. These models span species (mice, rats, rabbits and pigs) and several age groups to encompass the developmental time points and utilize various injury severities to reproduce the pathologies such as atrophy, ventriculomegaly, white matter injury, and behavioral impairment. This review focuses on the validation of these preclinical models using clinical observations of structural and functional impairment in the acute and chronic period following TBI. In addition, the limitations of the current animal models are discussed within the context of strategies for further development of clinically relevant outcomes and therapeutic strategies.