# Pre-Clinical Models of Traumatic Brain Injury—A Narrative Review Towards “Animal Neuro-ICUs”

## TL;DR

This paper reviews how to improve preclinical models of traumatic brain injury by incorporating neurocritical care principles and better experimental designs.

## Contribution

The paper proposes integrating neurocritical care into animal models and discusses factors like age and sex to improve translational relevance.

## Key findings

- Incorporating neurocritical care principles in animal models can enhance translational outcomes.
- Large and small animal models differ in their relevance to human TBI and should be chosen carefully.
- Variables like age, comorbidities, and sex significantly influence TBI outcomes and should be considered in experimental designs.

## Abstract

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.