Abstracts

Rationale: Traumatic brain injury (TBI) is a leading cause of symptomatic epilepsy in adults. Post-traumatic epilepsy (PTE) is characterized by spontaneous recurrent seizures that onset in the months or years following TBI. Although there are attempts to simulate PTE in animals, success has been limited due to lack of consistency in demonstrating spontaneous “epileptic” seizures after TBI. In this study, we sought to develop a valid model of PTE after penetrating TBI in mice.  Methods: We used a controlled cortical impact (CCI) paradigm to induce penetrating TBI often seen in human especially military personnel. Seizures were identified by 24/7 video-EEG monitoring for 120 days. Mice were perfused at 120 days after injury for neuropathology studies. Neurostereology was used to quantify lesion volume for whole brain and hippocampus. The extent of neuronal injury, neuroinflammation, mossy sprouting, seizure frequency, ripples, and other ictal parameters were evaluated.  Results: The overall incidence of epileptic seizures in surviving animals was 83% (n=15). Seizure duration varied from 10-75 s (average= 25 s), and average onset was 39 days after TBI. Seizures developed progressively, with a noted increase in frequency of seizures during weeks 11-14, and highest frequency at 8 seizures/week.  Extensive cortical and hippocampal tissue loss was observed at acute stages, with particular loss in the CA1 and DG regions. At 4 months post-injury, a massive persistent lesion was observed in TBI animals. Mossy fiber sprouting was more pronounced in the hippocampus of PTE animals, indicating morphological epileptogenesis.  Conclusions: These outcomes in mice are consistent with the electrophysiological and neuropathological sequelae observed in human PTE. This mouse PTE model is useful in assessing therapeutic interventions for preventing or attenuating the development of PTE. *Supported by DOD award #W81XWH-16-1-0660* Funding: *Supported by DOD award #W81XWH-16-1-0660*