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Electrical stimulation‐induced seizures in rats: A “dose‐response” study on resultant neurodegeneration

Perforant pathway stimulation (PPS) is used to study temporal lobe epilepsy in rodents. High‐frequency PPS induces acute seizures, which can lead to neuron death and spontaneous epilepsy. However, the minimum duration of PPS that induces neurodegeneration in naive rodents is unknown. Freely moving Sprague‐Dawley rats received one episode of continuous, bilateral PPS (range 1–180 min). Simultaneous recording from the hippocampal granule cell layer confirmed the presence of epileptiform activity and showed precisely when seizure activity was terminated by anesthesia. Fluoro‐Jade B staining, 1–7 days after PPS, determined neuronal degeneration. Thirty‐five minutes of continuous PPS produced no apparent neuron death anywhere in the brain. The minimum duration that caused neurodegeneration, which was confined to the dentate hilus, was 40 min. These data indicate that, in freely moving naive rats: (1) 40 min of PPS‐induced seizure activity is the threshold for brain cell death, and (2) dentate hilar neurons are the most vulnerable to PPS. Further studies are warranted to determine the threshold of epileptogenic neurodegeneration.