Abstracts

Traumatic brain injury is the single most important cause of acquired epilepsy and often manifests itself as complex partial seizures, which are frequently resistant to treatment with antiepileptic drugs. We have recently described, for the first time, an [italic]in vivo[/italic] model of posttraumatic epilepsy (PTE) in the rat where chronic recurrent seizures appear following a single episode of rostral lateral fluid percussion injury (rpFPI; D[rsquo]Ambrosio[italic] et al.[/italic], 2003). PTE was studied during the first 2 months post-injury. It was focal and seizures predominantly originated from the frontal-parietal neocortex at the injury site. However, rarer bilateral seizures originating from a different and undefined focus were also observed. To shed light on the posttraumatic epileptogenic mechanisms and on the generation of bilateral seizures, we studied rats up to 7 months post-injury. Severe in vivo rpFPI was induced in 32-35 days old Sprague Dawley male rats. Chronic electrocorticography (ECoG) with 5 epidural electrodes placed on frontalparietal and parietal occipital cortex, or paired epidural- and depth electrode recordings (in anterior and posterior ipsilateral hippocampus) were performed from 2 weeks to 7 months post-injury. Data are shown as mean[plusmn]standard error. Two epileptic foci were identified with different temporal evolution. The firing rate of the frontal-parietal neocortex was 2.04[plusmn]0.49 events/hour at 2-4 weeks and remained constant at 2.05[plusmn]0.86 events/hour at 17-18 weeks and at 2.6[plusmn]1.53 events/hour at 27-28 weeks post-injury. Conversely, the hippocampal firing rate was 0.090[plusmn]0.026 event/hour at 2-4 weeks and increased to 2.94[plusmn]1.25 at 26-27 weeks post-injury. The most common ictal behavioral at 2-4 weeks post-injury was stereotyped freeze-like pauses, sometimes followed by facial automatisms, and without loss of body posture. However, the ictal behavior 5 months post-injury typically consisted of stereotyped complex partial seizure with loss of posture with or without contralateral ictal limb dystonia. These results demonstrate for the first time that rfFPI-induced frontal-parietal epilepsy progresses to a multi-focal form of mesial-temporal lobe epilepsy. In addition, the different temporal evolution indicate distinct epileptogenic mechanisms at work in cortex and hippocampus. The data also extend the observed similarities between rpFPI-induced PTE and the human posttraumatic condition and further validate it as a clinically relevant model of PTE for antiepileptic and antiepileptogenic drug screening.
1) D[rsquo]Ambrosio, Fairbanks, Fender, Doyle, Born, Miller (2003) Posttraumatic epilepsy following fluid percussion injury in the rat. Brain. 2003 Nov 7 [Epub ahead of print]. (Supported by NIH/NINDS, grant NS 40823 (RD).)