The Study On The Expression And Significance Of TNF-α,Caspase3,NF-κB And Apoptosis In The Electrical Kindled Epilepsy Rat

[Objectives] Establishing the basolateral amygdala electrical (BLA) kindled rat epilepsy model, to test the expression of TNF-α,Caspase3,NF-кB and the apoptosis in epilepsy rats'hippocampi , to explore the role of cell death sign conversion path involving TNF-αin the development of epilepsy. [Methods] Bipolar electrodes were implanted in BLA of rats, through which the rats received chronic electrical stimuli for kindling. Their seizure processes were observed, and electroencephalogram (EEG) recording were performed during kindling and after kindled. The expression of TNF-α,Caspase3mRNA in kindled rats'hippocami were analyzed with semi-quantitative RT-PCR . The expression of Caspase3 and NF-кB was detected by the immunohistochemistry method. The apoptosis in the same location was tested by TdT-mediated dUTP nick end labeling (TUNEL) method. Control group, sham group and remedy groups were arranged for comparison. [Results] (1) Twenty five of 29 stimulated rats were kindled, for which mean stimuli needed was 12.64±4.12, and for produce 5 stage seizure 8.64±4.12. Their afterdischarge duration (ADD) recorded were between 21,450 ms and 119,720 ms. (2) The expression of TNF-α,Caspase3mRNA in kindled rats'hippocami were significantly increased(p < 0.01). There were statistically significant correlation between TNF-αand Caspase3(p < 0.05). (3) Expression of Caspase3 was upregulated obviously also in immunohistochemistry method(p < 0.05). The hippocami apoptotic cells in kindled rats were increased markedly than the control and sham groups(p < 0.01). There were statistically significant correlation between and Caspase3 and TUNEL dyed positive apoptosis cells, and the both of two were detected in CA1 and CA3 regions mostly. (4) The activity of NF-кB was transferred from plasm to nucleus in kindled rats, while the antiepileptic compounds have no marked influence on its expression. [Conclusions] The BLA electrical kindled rat model is similar highly to human temporal lobe epilepsy (TLE), and it is a ideal model to be used for the study of epileptic pathogenesis and the curative effect of antiepileptic compounds. Expression of TNF-α,Caspase3,NF-кB in kindled hippocami was increased markedly , and they are involved in the process of epileptic formation. Apoptosis is closely related to the process of kindling. TNF-α/TNFRⅠ-Caspase3 -Apoptosis, as a cell death sign conversion pathway plays a important role in the development of epilepsy. Antiepileptic compounds are neuroprotective to epileptic excitotoxic brain damage ,whose therapy mechanism are not so clear yet.