Pre-Clinical Models of Traumatic Brain Injury-A Narrative Review Towards "Animal Neuro-ICUs"

The presence of traumatic brain injury (TBI) is a critical determinant of post-traumatic mortality and morbidity. Not only is TBI one of the leading causes of death among severely injured patients, but it also substantially impacts long-term outcomes following severe trauma. Neurocritical care has a profound effect on outcomes following brain injury; nevertheless, its application in preclinical studies remains infrequent. This review therefore discusses strategies to improve the translational relevance of experimental TBI research, including the integration of neurocritical care principles in animal models. The review further addresses the impact of observation periods after injury and the selection of appropriate animal models (large vs. small animal models). In addition, commonly used injury induction methods-including controlled cortical impact (CCI), fluid percussion injury (FPI), weight-drop models, and blast injury paradigms-are discussed in terms of their reproducibility and clinical relevance. Finally, the review explores whether age, comorbidities, and sex influence TBI outcomes-and, if so, how these variables should be incorporated into experimental designs to improve translational fidelity.