Abstracts

Rationale: Epileptogenesis is a dynamic process involving several mechanisms that lead to a permanent state of spontaneous brain hyperactivity (both electrical and clinical manifestations) as well as a low threshold for brain excitability. The emergence of a hippocampal abnormal network associated with the imbalance of excitatory and inhibitory mechanisms plays a critical role in epileptogenesis; however, the main factor that triggers epileptogenesis remains unknown. Different experimental models that reproduce epileptogenesis are associated with status epilepticus, which leads to massive cell damage and metabolic disturbance. These models, however, do not allow for determining the main factor involved in epileptogenesis. Rapid kindling model in rodents offers one possibility for determining the progression of the electrical discharge in the stimulated hippocampal region without severe brain damage. Here, we evaluate hippocampal spontaneous epileptiform activity (SEA) and evoked hyperexcitability. Methods: Bipolar electrode units (Plastic One Inc., Roanoke, VA) were implanted in the dorsal right hippocampus. One week after surgery, kindling was achieved by stimulating six times daily for 4 days with a subconvulsive electrical stimulation (a 10-s train containing 50-Hz biphasic pulses of 75- to 200-μA amplitude for mice) at 30-min intervals. In order to obtain SEA, 24 stimulations were added following the 4th day of kindling. As a positive control for SEA, a group of mice with the electrode implanted in dorsal hippocampus were injected with kainic acid (KA 35 mg/Kg, ip). Seizure severity and EEG were analyzed for one week after kindling and KA injection. Results: For one week after kindling acquisition, spontaneous interictal spikes with high frequency and amplitude were present. Also epileptiform activity associated with high frequency oscillation and score 2 (Racine’s score) was observed. Similar discharges were observed after status epilepticus induced by kainic acid. An increased number of spikes and seizure severity were evoked from the hippocampus immediately after subconvulsive stimulations one week after kindling acquisition. Conclusions: These results suggest that extended rapid kindling in C57Bl/6 mice elicits hippocampal SEA associated with limbic seizure events. The early interictal spikes could work as a kindling-like process that could promote development of chronic limbic seizures