Novel Approaches to Prevent Epileptogenesis After Traumatic Brain Injury

Neurotherapeutics. 2021 Jul;18(3):1582-1601. doi: 10.1007/s13311-021-01119-1. Epub 2021 Sep 30.


Traumatic brain injury (TBI) is defined as an alteration in brain function or other evidence of brain pathology caused by an external force. When epilepsy develops following TBI, it is known as post-traumatic epilepsy (PTE). PTE occurs in a subset of patients suffering from different types and severities of TBI, occurs more commonly following severe injury, and greatly impacts the quality of life for patients recovering from TBI. Similar to other types of epilepsy, PTE is often refractory to drug treatment with standard anti-seizure drugs. No therapeutic approaches have proven successful in the clinic to prevent the development of PTE. Therefore, novel treatment strategies are needed to stop the development of PTE and improve the quality of life for patients after TBI. Interestingly, TBI represents an excellent clinical opportunity for intervention to prevent epileptogenesis as typically the time of initiation of epileptogenesis (i.e., TBI) is known, the population of at-risk patients is large, and animal models for preclinical studies of mechanisms and treatment targets are available. If properly identified and treated, there is a true opportunity to prevent epileptogenesis after TBI and stop seizures from ever happening. With that goal in mind, here we review previous attempts to prevent PTE both in animal studies and in humans, we examine how biomarkers could enable better-targeted therapeutics, and we discuss how genetic variation may predispose individuals to PTE. Finally, we highlight exciting new advances in the field that suggest that there may be novel approaches to prevent PTE that should be considered for further clinical development.

Keywords: Anti-epileptogenesis; Biomarker; Epileptogenesis; Post-traumatic epilepsy; Treatment.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Brain Injuries, Traumatic / genetics
  • Brain Injuries, Traumatic / metabolism
  • Brain Injuries, Traumatic / therapy*
  • Cell- and Tissue-Based Therapy / methods
  • Epilepsy, Post-Traumatic / genetics
  • Epilepsy, Post-Traumatic / metabolism
  • Epilepsy, Post-Traumatic / therapy*
  • Genetic Therapy / methods*
  • Genetic Variation / drug effects
  • Genetic Variation / genetics*
  • Humans
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / metabolism


  • Anti-Inflammatory Agents
  • Anticonvulsants
  • Inflammation Mediators