| Objective:Epilepsy is a common nervous system disease; cognitive impairments significantly contribute to reduced quality of life in patients with epilepsy.Multiple factors can contribute to this problem,including the etiology of the epilepsy,seizure type,frequency and duration,localization of the epileptic focus,age at onset of epilepsy,physiological and structural changes in the brain secondary to seizures and social fators.The potential for antiepileptic drugs (AEDs) to negatively impact cognitive abilities is of significant concern because they are the major therapeutic modality for control of seizures. Levetiracetam (LEV) and topiramate (TPM) are considered highly effective novel antiepileptic drugs (AEDs) in the treatment of epilepsies.Due to the different of the animal model, experiment technology and study approach, the conclusion comparability was limited.This study was injected Kainic acid (KA) into rat's right CA3 hippocampal region by stereotactic operation to induce epilepsy.It can eliminate the effect of confounding factors of age, educational background and course of disease et al. in human beings. By temporal lobe epilepsy rat model to study the learning and memory disorders systematically. This study investigated their influence of different doses of Levetiracetam (LEV) and topiramate (TPM) on rats, cognitive functions by morris water maze test, if the effects of Levetiracetam (LEV) and topiramate (TPM) on rats, cognitive functions are dose-dependment. Immunohistochemistry technique was used to investigate the expression of the cell death regulatory gene Bcl-2 and bax.Methods: 78 health male Sprague–Dawley rats weighting (100±10g) were used and divided into normal group and kainic acid induced seizure group at random. And then kainic acid induced seizure group divided into seizure control group,topiramate 20mg/kg treatment group, topiramate 40mg/kg treatment group, topiramate 80mg/kg treatment group, levetiracetam 200mg/kg treatment group, levetiracetam 400mg/kg treatment group ,levetiracetam 800mg/kg treatment group. Eight rats were in normal control, and ten rats in each other groups. Kainic acid (KA) 3ug/kg was injected into rat's right CA3 hippocampal region by stereotactic operation to induce epilepsy.The normal control rats received an equal volume of saline vehicle .The rats were assigned a score for seizure behaviors using the scale modified from Racine. Seizures were monitored so that all behavioral changes were recorded. After they were kindling, then each groups were treated by antiepileptic drugs (AEDs),the normal control group and seizure control group received an equal volume of distilled water. Six weeks later,8 groups were tested in Morris water maze.After the Morris water maze test,the rats were perfused with cold saline,fixed with 4% paraformaldehyde in 0.1 N phosphate-buffered saline (PBS).The brains were removed and postfixed with 4% paraformaldehyde in phosphate-buffered saline and processed for paraffin imbedding. Immunohistochemistry technique was used to investigate the expression of the cell death regulatory gene Bcl-2 and bax.Statistical analysis was run using SPSS 11.5 software. The measurement data was indicated the mean and standard deviation (SD). One-Way ANOVA and Dunnett-t test were used in the study.Results: The results of place navigation: The average time spent by the rats of seizure group was longer than normal group in each day and had statistical significance compared with the normal group. The average time spent by the rats of different doses of topiramate treatment groups were longer than seizure group in each day and had statistical significance in topiramate 40mg/kg and 80mg/kg treatment groups compared with the seizure group. The average time of levetiracetam 800mg/kg treatment group had no statistical significance in each day compared with the seizure group. On the third day, the average time of levetiracetam 200mg/kg and 400mg/kg treatment group had statistical significance compared with the seizure group.The results of spatial probe: The times of crossing the platform of the rats in the seizure group were lessened and had statistical significance compared with the normal group. The times of crossing the platform of the rats in the different doses of topiramate treatment groups were lessened and had statistical significance in topiramate 40mg/kg and 80mg/kg treatment groups compared with the seizure group. The different doses of levetiracetam treatment groups had no statistical significance compared with the seizure group.Immunohistochemistry stains show that the express of Bcl-2 were 2.50±0.93,2.30±0.82,3.90±1.10,8.90±2.28,9.22±1.56,4.00±1.15,9.11±1.62,10.10±1.66.Three were no statistical significance between the seizure group and the normal group. There was more expression of the Bcl-2 in TPM 20mg/kg treatment group, LEV200mg/kg treatment group compared with the seizure group. There were more expression of the Bcl-2 in TPM 40mg/kg, 80mg/kg treatment group and LEV400mg/kg, 800mg/kg treatment group and had statistical significance compared with the seizure group.The express of Bax were 28.00±5.07,55.30±8.50,45.50±9.97,39.1±5.97,30.89±7.69,45.10±10.03,41.11±7.44,37.00±7.50. There were more expression of the Bax in seizure group and had statistical significance compared with the normal control. The express of Bax in TPM20mg/kg, 40mg/kg, 80mg/kg treatment groups and LEV200mg/kg, 400mg/kg, 800mg/kg treatment groups were lessened and had statistical significance compared with the seizure group.Conclusion: The effects of topiramate on rats'cognitive functions are dose-dependment. Low dosage of topiramate didn't affect the cognitive functions of rats and the medium dosage and high dosage of topiramate damage the the rats'cognitive functions. The different doses of levetiracetam didn't affect the rats'cognitive functions. The different doses of topiramate and levetiracetam inhibited the expression of Bax, the medium and high dose of topiramate, levetiracetam induced the expression of Bcl-2, and their expression of Bax and Bcl-2 may be involved in the protective effects of neuron. |
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