Development of post-traumatic epilepsy after controlled cortical impact and lateral fluid-percussion-induced brain injury in the mouse

Abstract

The present study investigated the development of hyperexcitability and epilepsy in mice with traumatic brain injury (TBI) induced by controlled cortical impact (CCI) or lateral fluid-percussion injury (FPI), which are the two most commonly used experimental models of human TBI in rodents. TBI was induced with CCI to 50 (14 controls) and with lateral FPI to 45 (15 controls) C57BL/6S adult male mice. The animals were followed-up for 9 months, including three 2-week periods of continuous video-electroencephalographic (EEG) monitoring, and a seizure susceptibility test with pentylenetetrazol (PTZ). In the end, the animals were perfusion-fixed for histology. The experiment included two independent cohorts of animals. Late post-traumatic spontaneous electrographic seizures were detected in 9% of mice after CCI and 3% after lateral FPI. Eighty-two percent of mice after CCI and 71% after lateral FPI had spontaneous epileptiform spiking on EEG. In addition, 58% of mice with lateral FPI showed spontaneous epileptiform discharges. A PTZ test demonstrated increased seizure susceptibility in the majority of mice in both models, compared to control mice. There was no further progression in the occurrence of epilepsy or epileptiform spiking when follow-up was extended from 6 to 9 months. The severity of cortical or hippocampal damage did not differentiate mice with or without epileptiform activity in either model. Finally, two independent series of experiments in both injury models provided comparable data demonstrating reproducibility of the modeling. These data show that different types of impact can trigger epileptogenesis in mice. Even though the frequency of spontaneous seizures in C57BL/6S mice is low, a large majority of animals develop hyperexcitability.