Post-traumatic epilepsy: Insights from human cortical contused tissue.

Abstract

Traumatic brain injury is a significant risk factor for the development of post-traumatic epilepsy (PTE), posing a major clinical challenge. This review discusses the critical role of GABAergic interneurons and reactive astrogliosis in the pathophysiology of post-traumatic epilepsy, integrating findings from our research group within the traumatic brain injury context with recent literature to highlight the impact of excitation-inhibition imbalance. We analyzed alterations in interneuron populations, specifically subtypes expressing the calcium-binding proteins parvalbumin, calretinin, and calbindin, and their association with an increased risk of epileptogenesis after TBI. Furthermore, we detail the role of reactive astrogliosis, elucidating how dysregulated astrocytic functions, including impaired glutamate homeostasis and aberrant calcium signaling, contribute to an environment conducive to seizure activity. Increased expression of glial fibrillary acidic protein and crystallin alpha-B in reactive astrocytes identified in contused human tissue suggests their involvement in exacerbating epileptogenic circuits. Our findings emphasize the intricate interactions between GABAergic interneurons and astrocytes, underscoring the need for a comprehensive understanding of the mechanisms underlying post-traumatic epilepsy. By bridging our group's data with existing evidence, this review establishes a foundation for future studies aimed at validating systemic biomarkers and developing targeted therapies to prevent or mitigate epilepsy progression following TBI. These insights are essential for addressing the complexities of drug-resistant epilepsy in affected patients.