Features of animal models of complex partial epilepsy established through unilateral,bilateral and alternate-side kindling at hippocampus of rats

BACKGROUND： Electrical stimulation kindling model, having epilepsy-inducing and spontaneous seizure and other advantages, is a very ideal experimental animal model. But the kindling effect might be different at different sites. OBJECTIVE： To compare the features of animal models of complex partial epilepsy established through unilateral, bilateral and alternate-side kindling at hippocampus and successful rate of modeling among these 3 different ways. DESIGN： A randomized and controlled animal experiment SETTING： Department of Neurology, Qilu Hospital, Shandong University MATERIALS： Totally 60 healthy adult Wistar rats, weighing 200 to 300 g, of either gender, were used in this experiment. BL-410 biological functional experimental system （Taimeng Science and Technology Co. Ltd, Chengdu） and SE-7102 type electronic stimulator （Guangdian Company, Japan） were used in the experiment. METHODS： This experiment was carried out in the Experimental Animal Center of Shandong University from April to June 2004. After rats were anesthetized, electrode was implanted into the hippocampus. From the first day of measurement of afterdischarge threshold value, rats were given two-square-wave suprathreshold stimulation once per day with 400 μA intensity, 1ms wave length, 60 Hz frequency for 1 s duration. Left hippocampus was stimulated in unilateral kindling group, bilateral hippocampi were stimulated in bilateral kindling group, and left and right hippocampi were stimulated alternately every day in the alternate-side kindling group. Seizure intensity was scored： grade 0： normal, 1： wet dog-like shivering, facial spasm, such as, winking, touching the beard, rhythmic chewing and so on; 2： rhythmic nodding; 3： forelimb spasm;4： standing accompanied by bilateral forelimb spasm;5： tumbling, losing balance, four limbs spasm. Modeling was successful when seizure intensity reached grade 5. t test was used for the comparison of mean value between two samples. MAIN OUTCOME MEASURES： Comparison of the successful rate of modeling, the times of stimulation to reach intensity of grade 5, the lasting time of seizure of grade 3 of rats in each group. RESULTS： Four rats of alternate-side kindling group dropped out due to infection-induced electrode loss, and 56 rats were involved in the result analysis. The successful rate of unilateral kindling group, bilateral kin- dling group and alternate-side kindling group was 55%（11/20）,100%（16/16）and 100%（20/20）, respective- ly. The stimuli to reach the grade 5 spasm were significantly more in the bilateral kindling group than in the unilateral kindling group [（30.63±3.48）, （19.36±3.47）times, t=8.268, P 〈 0.01], and those were significantly fewer in the alternate-side kindling group than in the unilateral kindling group [（ 10.85±1.98）times, t=-8.744, P 〈 0.01]. The duration of grade 3 spasm was significantly longer in the bilateral kindling group than in the unilateral kindling group [（9.75±2.59）, （3.21 ±1.58）days,t=-8.183,P 〈 0.01], Among 20 successful rats of al- ternate-side kindling group, grade 5 spasm was found in the left hippocampi of 11 rats, but grade 3 spasm in their right hippocampi; Grade 5 spasm was found in the right hippocampi of the other 9 rats, grade 4 spasm in the left hippocampus of 1 rat and grade 3 of 8 rats. CONCLUSION ： The speed of establishing epilepsy seizure model by alternate-side kindling is faster than that by unilateral kindling, while that by bilateral kindling is slower than that by unilateral kindling. The successful rate is very high to establish complex partial epilepsy with alternate-side or bilateral kindling. Epilepsy seizure established by alternate-side kindling has antagonistic effect of kindling and the seizure duration of grade 3 spasm is prolonged.