Abstracts

Rationale:
Epileptogenesis, the pathological process by which a normal brain becomes an epileptic brain, is most commonly considered following the epileptogenic insult and prior to the first seizure. However this process may continue following the first seizure and may contribute to progression in epilepsy. We present a model of post-traumatic epilepsy in rat in which ictal electrographic activity demonstrates a regular pattern of evolution following the first seizure.
Method:
Rats (n = 16) from a unique, Perforant Path Kindling Susceptible (PPKS) strain, selectively bred from a Sprague-Dawley (SD) background for >15 generations were given a traumatic brain injury by controlled cortical impact (3mm blunt impactor, 6m/s, 500msec dwell time) to the posterior cortex under isoflurane anesthesia (2% in O2 for 5 minutes prior to delivery of a CCI). A head cap attached to four epidural screw electrodes (left and right, anterior and posterior) was also placed for chronic recording of electrographic activity. Rats were monitored by video-EEG for 4-6 hours, 2-3 days per week, for 6 months following injury.
Results:
Following CCI, PTE developed in 9 of the 16 PPKS rats. Seizures with a semiology of behavioral arrest and an electrographic correlate appeared at a mean of 8.4 weeks following CCI. Electrographically seizures consist of rhythmic polyspikes, typically beginning with a lateralized (over the injured hemisphere) appearance and becoming generalized over time. Seizure duration increases over time, with early seizures typically ∼6 seconds initially and lasting 90–120 seconds later in the course. Ictal power is initially maximal over the injured hemisphere, but declines with duration of epilepsy while ictal power increases over the uninjured hemisphere. Interhemispheric coherence during ictal activity increases over time. Ictal entropy decreases and ictal kurtosis increases with duration of post-traumatic epilepsy.
Conclusion:
These findings demonstrate patterns of change in ictal electrographic activity in a rat model of post-traumatic epilepsy which may correlate with progression of epilepsy following the first seizure. This evolution may represent an electrographic biomarker for progression of epilepsy in an animal model. Correlation of these electrographic changes with cellular, molecular, and genetic changes may provide insights into the progression of epilepsy after the first seizure and provide a model for the testing of therapeutic interventions targeting progression of epilepsy.
Funding:
:VA CDA-2 IK2BX002986 (RJK) Defense Hypothesis Development Award DR080424 (TPS)