SUMMARY

We recently described an in vivo model of posttraumatic epilepsy (PTE) in the rat where chronic spontaneous recurrent seizures appear following a single episode of fluid percussion injury (FPI; D'Ambrosio et al., 2003). PTE, studied during the first 2 months post-injury, 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. In-vivo paired epidural and depth-electrode recordings indicated the anterior hippocampus evolves into an epileptic focus which initiates bilateral seizures. The rate of frontal-parietal seizures remained constant over time post-injury, while the rate of hippocampal seizures greatly increased over time, suggesting different mechanisms mediate neocortical and hippocampal posttraumatic epileptogenesis. Because of different temporal evolution of these foci, the epileptic syndrome was characterized by predominant frontal-parietal seizures early after injury, but by predominant mesio-temporal seizures at later time points. Pathological analysis demonstrated progressive hippocampal and temporal cortex pathology that paralleled the increase in frequency and duration of bilateral seizures. These results demonstrate that FPI-induced frontal-parietal epilepsy (FPE) progresses to mesial-temporal lobe epilepsy (MTLE) with dual pathology. These observations establish numerous similarities between FPI-induced and human PTE and further validate it as a clinically relevant model of PTE.