In search of antiepileptogenic treatments for post-traumatic epilepsy

Post-traumatic epilepsy (PTE) is diagnosed in 20% of individuals with acquired epilepsy, and can impact significantly the quality of life due to the seizures and other functional or cognitive and behavioral outcomes of the traumatic brain injury (TBI) and PTE. There is no available antiepileptogenic or disease modifying treatment for PTE. Animal models of TBI and PTE have been developed, offering useful insights on the value of inflammatory, neurodegenerative pathways, hemorrhages and iron accumulation, calcium channels and other target pathways that could be used for treatment development. Most of the existing preclinical studies test efficacy towards pathologies of functional recovery after TBI, while a few studies are emerging testing the effects towards induced or spontaneous seizures. Here we review the existing preclinical trials testing new candidate treatments for TBI sequelae and PTE, and discuss future directions for efforts aiming at developing antiepileptogenic and disease-modifying treatments. •Post-traumatic epilepsy (PTE) is a common form of acquired epilepsy.•There is no available treatment that can prevent or stop PTE.•Animal models of PTE have provided insight on multiple pathways that could provide therapy targets.•Inflammation, neurodegeneration, cholinergic signaling, Ca2+ channels, iron stores are candidate PTE treatment targets.