Abstracts

Various brain insults, such as status epilepticus, encephalitis, and head trauma are associated with an elevated risk of epilepsy later in life. Up to 50% of patients with penetrating brain injury can develop epilepsy. To investigate molecular and cellular mechanisms associated with increased epileptogenesis after head trauma, our first challenge was to develop an animal model of head trauma-induced epileptogenesis.
Head trauma was conducted by fluid percussion injury in adult Spraque-Dawley rats (n=26). Five weeks after head trauma 3 cortical and 1 hippocampal electrodes were implanted for video-EEG recordings. To assess the occurrence of epileptic seizures, animals were monitored with a continuous (24h/day) video-EEG monitoring for 7 days at different time points (8-10 we, 19-20 we, 27-29 and 36-38 we) after trauma. Behavioral seizure severity was scored by modified Racine scoring scale. After video-EEG recordings animals were perfused for histology.
Seventeen surviving animals were followed in long-term. Seven out of 17 (41%) of animals with head trauma developed epilepsy. The mean seizure frequency was 0.30 [plusmn] 0.33 sz/day (range 0.04-1.0, median 0.18). The mean seizure duration was 102 [plusmn] 41 sec (range 61-134 sec, median 86), and the mean behavioral seizure severity 3.2 [plusmn] 1.7 (range 1.0-5.0, median 4.0). Histologic analysis showed that mossy fiber sprouting was denser in epileptic animals compared to nonepileptic traumatized or sham-operated control animals. Further, sprouting was most intense in the septal hippocampus ipsilaterally.
This study shows for the first time that spontaneous seizures develop in a subpopulation of rats as a sequel of cortical fluid-percusssion injury. This new model of human posttraumatic epilepsy offers a tool to understand molecular mechanisms of epileptogenesis and can be used to test novel antiepileptogenic compounds in preclinical design.
[Supported by: Finnish Cultural Foundation, Sigrid Juselius Foundation, Vaajasalo Foundation]