Traumatic brain injury and epilepsy: Underlying mechanisms leading to seizure  Brandon P. Lucke-Wold, Linda Nguyen, Ryan C. Turner, Aric F. Logsdon, Yi-Wen Chen, Kelly E. Smith, Jason D. Huber, Rae Matsumoto, Charles L. Rosen, Eric S. Tucker, Erich Richter  Seizure - European Journal of Epilepsy  Volume 33, Pages 13-23 (December 2015) DOI: 10.1016/j.seizure.2015.10.002 Copyright © 2015 Terms and Conditions

Fig. 1 The initial acute injury (hours–days) following TBI induces glutamate excitability and sclerosis. Reactive oxygen species are generated from the resulting hyperexcitability, which damage the cell. This process is regulated by microRNAs. At subacute time points (days–weeks) inflammation occurs from activated toll-like receptors and non-NMDA glutamate receptors. These further insults exacerbate the damage caused by glutamate toxicity and allow free iron to enter the cell. Over time (months–years) this injury contributes to tau aggregation. Tau interacts with zinc to generate further free radical damage reducing the threshold for late onset seizure. Seizure - European Journal of Epilepsy 2015 33, 13-23DOI: (10.1016/j.seizure.2015.10.002) Copyright © 2015 Terms and Conditions

Fig. 2 Novel treatments of epilepsy are often targeted toward the regulation of GABA and glutamate ligand gated channels as well as voltage gated cation channels. Previously explored treatments include: inhibition of cannabinoid receptor CB1, ketogenic diets, and regulation of vesicle activity. These treatments warrant further investigation. Seizure - European Journal of Epilepsy 2015 33, 13-23DOI: (10.1016/j.seizure.2015.10.002) Copyright © 2015 Terms and Conditions