Association of the severity of cortical damage with the occurrence of spontaneous seizures and hyperexcitability in an animal model of posttraumatic epilepsy

SummaryPosttraumatic epilepsy is a common consequence of traumatic brain injury in humans. Major predictors for the development of posttraumatic epilepsy include the severity of injury and occurrence of cortical contusions. The effect of the size or location of the cortical lesion on the risk of epileptogenesis, however, is poorly understood. Here, we investigated the extent and location of cortical damage and its association with a lowered seizure threshold and the occurrence of spontaneous seizures in rats (n = 77) that had experienced moderate or severe lateral fluid-percussion brain injury (FPBI) 12 months earlier. Spontaneous seizures were detected with video-electroencephalography monitoring and a lowered seizure threshold was determined based on a pentylenetetrazol (PTZ) test. Cortical atrophy was evaluated from thionin-stained sections using the Cavalieri estimation in four different experiments in which rats developed either spontaneous recurrent seizures (i.e., epilepsy) or a lowered seizure threshold. Our data show that damage to the cortex ipsilateral to the injury was more severe and extended more caudally in epileptic animals than in those without epilepsy (p < 0.05 and p < 0.001 for 2 independent experiments). Further, the extent of the cortical damage correlated positively with chronically increased hyperexcitability (number of spikes in PTZ test) in animals with traumatic brain injury (r = −0.54, p < 0.05; r = −0.72, p < 0.01 for 2 independent experiments). Specifically, cortical lesions located at the level of the perirhinal, entorhinal, and postrhinal cortices were associated with a lowered seizure threshold and seizures. The severity of the cortical injury did not correlate with the severity of hippocampal damage. These findings indicate that, like in humans, the severity of cortical injury correlates with epileptogenesis and epilepsy in an experimental model of posttraumatic epilepsy.