Abstracts

Rationale: Traumatic brain injury (TBI) is one of the major risk factors for the development of epilepsy. Development of animal's models is a key for understanding the mechanisms, search of surrogate markers, and development of novel treatments for post-traumatic epilepsy (PTE). Lateral fluid-percussion (LFP) TBI in rat is the most widely used animal model of human closed head brain injury, and as we have previously shown, epilepsy develops in about 50% of the rats. The present study investigated whether LFP also leads to the development of epilepsy in mice, which would be useful, for example, for studies investigating the effects of genetic background or genetic mutations on the development of PTE. Methods: LFP brain injury was induced in male C57Bl/6J mice (22-24g). Injury magnitude was 3.0 atm and mortality within the first 48 h was 20%. Cortical electrodes were inserted into the skull for continuous video-EEG recording at 22 weeks post-injury (15 injured, 7 controls). To detect the occurrence of spontaneous seizures, video-EEG monitoring was started at 1 week after electrode implantation. After 2 weeks of monitoring, we performed pentyleneterazol (PTZ, 50 mg/kg, i.p.) seizure threshold test under video-EEG to detect the occurrence of lowered seizure threshold, and continued the monitoring for another 2 weeks. In seizure threshold test, we assessed the latency to the first seizure, number of epileptiform discharges (ED), duration of EDs, and total number of spikes within 1 hour after PTZ injection Results: During the first 2 weeks of video-EEG monitoring that was conducted 6 months post-injury, 1 mouse had 2 spontaneous seizures lasting 8 and 10 sec. PTZ test showed that latency to the first seizure was reduced (p<0.05) and total number of spikes was increased (p<0.05) in injured mice as compared to controls. Conclusions: The present 6-months interim data from a 9-months follow-up study show that LFP brain injury leads to the development of lowered seizure threshold and even spontaneous seizures in mice. The data suggest that LFP brain injury may be a useful model for studies investigating the effects of various genetic manipulations of the development of PTE. Supported by the Academy of Finalnd, the Sigrid Juselius Foundation, and CURE (Citizens United for Research in Epilepsy)