Models of traumatic brain injury: modern approaches, classification, and research perspectives

Traumatic brain injury represents one of the most complex biomedical challenges, affecting millions of people worldwide each year. Various experimental and theoretical models are used to understand the pathophysiology of traumatic brain injury and to develop effective therapeutic strategies. This review focuses on three main groups of models: theoretical (in silico), cellular (in vitro), and animal (in vivo). Theoretical models of traumatic brain injury are based on mathematical approaches and computer simulations to analyze mechanical brain injuries, edema processes, ischemia, and neuroinflammation. In silico approaches provide high precision and reproducibility but require proper validation with biological data. Cellular models include the cultivation of neurons, astrocytes, microglia, and brain organoids, which are subjected to mechanical or chemical factors that mimic traumatic brain injury. These systems allow researchers to study cellular and molecular mechanisms such as apoptosis, neuroinflammation, and regeneration. However, in vitro models are limited by the absence of a systemic response characteristic of an entire organism. Animal models are considered the “gold standard” for studying traumatic brain injury. These involve direct mechanical impacts on the brains of animals (e.g., mice, rats, pigs), enabling the reproduction of clinical aspects of trauma, including behavioral and pathophysiological changes. Despite their high physiological relevance, in vivo models face ethical limitations and challenges in extrapolating results to humans. This article provides an overview of modern approaches to traumatic brain injury modeling, including their classification, characteristics, advantages, and limitations. The data presented may serve as a foundation for developing more effective treatment and rehabilitation strategies for traumatic brain injury patients.