title: Traumatic brain injury and epilepsy: Underlying mechanisms leading to seizure.
abstract: Post-traumatic epilepsy continues to be a major concern for those experiencing traumatic brain injury. Post-traumatic epilepsy accounts for 10-20% of epilepsy cases in the general population. While seizure prophylaxis can prevent early onset seizures, no available treatments effectively prevent late-onset seizure. Little is known about the progression of neural injury over time and how this injury progression contributes to late onset seizure development. In this comprehensive review, we discuss the epidemiology and risk factors for post-traumatic epilepsy and the current pharmacologic agents used for treatment. We highlight limitations with the current approach and offer suggestions for remedying the knowledge gap. Critical to this pursuit is the design of pre-clinical models to investigate important mechanistic factors responsible for post-traumatic epilepsy development. We discuss what the current models have provided in terms of understanding acute injury and what is needed to advance understanding regarding late onset seizure. New model designs will be used to investigate novel pathways linking acute injury to chronic changes within the brain. Important components of this transition are likely mediated by toll-like receptors, neuroinflammation, and tauopathy. In the final section, we highlight current experimental therapies that may prove promising in preventing and treating post-traumatic epilepsy. By increasing understanding about post-traumatic epilepsy and injury expansion over time, it will be possible to design better treatments with specific molecular targets to prevent late-onset seizure occurrence following traumatic brain injury.
authors.affiliation: Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV 26506, USA; The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV 26506, USA.
authors.forename: Brandon P
authors.initials: BP
authors.lastname: Lucke-Wold
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26506, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Nguyen
authors.affiliation: Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV 26506, USA; The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV 26506, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Turner
authors.affiliation: The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV 26506, USA; Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26506, USA.
authors.forename: Aric F
authors.initials: AF
authors.lastname: Logsdon
authors.affiliation: The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV 26506, USA.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26506, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Smith
authors.affiliation: The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV 26506, USA; Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26506, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Huber
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26506, USA; College of Pharmacy, Touro University California, 1310 Club Drive, Vallejo, CA 94592, USA.
authors.forename: Rae
authors.initials: R
authors.lastname: Matsumoto
authors.affiliation: Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV 26506, USA; The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV 26506, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Rosen
authors.affiliation: The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV 26506, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Tucker
authors.affiliation: Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV 26506, USA; The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV 26506, USA. Electronic address: eorichter@hsc.wvu.edu.
authors.forename: Erich
authors.initials: E
authors.lastname: Richter
mesh_terms: D001930:Brain Injuries / Q000150:complications* / Q000453:epidemiology*; D004827:Epilepsy / Q000453:epidemiology* / Q000209:etiology*; D004834:Epilepsy, Post-Traumatic / Q000209:etiology*; D006801:Humans; D012307:Risk Factors
keywords: Epilepsy models; Ketogenic therapy; Neuroinflammation; Post-traumatic epilepsy; Traumatic brain injury