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BACKGROUND: Physiological convulsive thresholds degrade when the brain is in some pathologic states; thus, a level of stimulus that cannot provoke a convulsion may evoke a seizure or epileptic seizure.OBJECTIVE: To investigate the changes that occur in the brain when the physiological convulsive threshold becomes pathological, and to determine what differences occur in pathological and physiological convulsive thresholds during the development of epilepsy.DESIGN: A randomized controlled animal experiment.SETTING: Research Institute of Epilepsy of Shanxi Medical University; Department of Neurology, The Third Hospital of Shanxi Medical University; Research Institute of Function of Shanxi Medical University.MATERIALS: Thirty-six female Wistar rats were selected for this study. The rats were obtained from the experimental animal center of Shanxi Medical University. All laboratory procedures complied with animal ethical standards. The animals were randomly divided into three groups: a strong current group, a weak current group and a control group, with 12 rats in each group. An automatic determinator of seizure threshold was made at Shanxi Medical University and Taiyuan University of Technology. Two bipolar stainless steel stimulating electrodes and an electrode connector (diameter 1.2 mm) were made at Taiyuan University of Technology.METHODS: This study was performed in the laboratory of Research Institute of the Epilepsy of Shanxi Medical University between December 2005 and August 2006. The threshold of localized seizures was measured by performing direct cortical stimulation in rats under anesthesia. After 1 week of post-operative recovery, electric stimulation was started with three different kinds of stimulation. Seizure activity was induced by a ramp-shaped single train of biphasic pulses (50 Hz, total pulse duration of 2 ms, increasing from 0 to 2 000 μA in 15 seconds). The threshold of localized seizures (TLS) has been defined as the minimum current intensity necessary to provoke convulsion of the forelimbs and/or facial muscles. Up to the TLS, if stimulation continued, the current intensity necessary to provoke the generalized seizures is called the threshold of generalized seizures (TGS). If stimulation is continued for about 2 seconds when the TGS is reached, rats still showed generalized clonic activity after stimulation ceased. When seizures stopped, a short period of immobility can be observed. The current intensity is called the threshold of prolonged seizures (TPS). The rats in the strong current group were stimulated up to the current level required to reach the TPS. In the course of stimulation, first, the TLS was recorded, then the TGS, and finally the TPS. The stimulation interval in one session was 10 minutes, repeated twice daily. The rats in the weak current group were only stimulated up to the current levels required to reach the TGS; first, the TLS was recorded and then the TGS was measured at the same time as the strong current group. Control animals were also equipped with a full electrode set and placed in the same conditions, but no stimulation took place, only electroencephalogram (EEG) recording at the same times as the experimental groups.MAIN OUTCOME MEASURES: ① Stimulation of the two experimental groups lasted for 11 weeks and then observation of their behavior and electroencephalogram recording continued for 4 weeks. The control group was also observed over a total of 15 weeks. ② Observing neuronal damage/loss in the hippocampus with a light microscope using a 250× visual field.RESULTS: All 36 Wistar rats were included in the final analysis. At the beginning of the experiment, the convulsive thresholds were all above 1 100 μA, although there were significant individual variations among rats of the same group. Those thresholds quickly declined during the initial 4 weeks of repetitive electrical stimulation. The convulsive thresholds approached a constant level in the 10th week after commencement of stimulation. There were no significant changes in thresholds when stimulations lasted longer; the convulsive thresholds and the variations in rats of the same group were significantly lower than at the beginning of the trial (P < 0.01). An interictal discharge was also recorded in the 3rd week in the strong current group, and in the 8th week in the weak current group; these discharges were concomitant with neuronal damage and loss in the hippocampus. There was no abnormality observed in the control group. CONCLUSION: These findings indicated that the convulsion threshold in the brain should be divided into two stages: a physiological convulsive threshold and a pathological convulsive threshold (epileptic threshold). The epileptic threshold is created by pathologically acquired factors, which give rise to brain damage. The increase in the intensity of these pathologically acquired factors led to aggravation of damage.