The Fluid Percussion Injury Model of Traumatic Brain Injury: Insights into Post-Traumatic Epilepsy and Comorbidities

Traumatic brain injury (TBI) affects millions of people each year and can lead to persistent neurological disorders, including post-traumatic epilepsy (PTE). Animal models of concussion and TBI, developed since the late nineteenth century, provide a means to investigate injury progression and its consequences under controlled conditions. The lateral fluid percussion injury (LFPI) model is widely used to study both TBI and post-traumatic epileptogenesis. PTE is often resistant to antiseizure medications, and variability among experimental models (e.g., strain, injury, surgical, and physiological differences) remains a major obstacle to developing antiepileptogenic treatments. Understanding the factors that influence model reproducibility is therefore essential. This review first examines the development of the LFPI model and the experimental factors that influence PTE outcomes. It then considers the cellular mechanisms of post-injury hyperexcitability and the affective, cognitive, and neurodegenerative changes associated with LFPI. Together, these findings indicate the value of the model while defining the limits of its application to human disease.