Effect and Mechanism of Carbamazepine on SCN1A Expression in Temporal Lobe Epilepsy Rats
Xiang Yu Wang, Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangdong 510630, China, E-mail: email@example.com
Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangdong 510630, China
To investigate the effect of carbamazepine treatment on the expression of SCN1A in temporal lobe epilepsy and its mechanism of action. 90 male Wistar rats were randomly divided into 30 rats each in the carbamazepine group, model group and blank control group, in which the temporal lobe epilepsy rat model was established using lithium-pilocarpine in the carbamazepine and model groups. After successful modeling, the carbamazepine group was given carbamazepine solution at a concentration of 16 mg/ml in a dose of 2 ml once/d; the model group was not given any drug treatment, and distilled water was given 2 ml/ time/d. The normal control group was fed routinely without any special treatment. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction and Western blot assay were used to detect the changes of SCN1A expression level in each group. Polymerase chain reaction results showed that the expression of SCN1A messenger ribonucleic acid in the model group was significantly higher than that in the control group and the carbamazepine group, and the difference was statistically significant (p<0.05), and the SCN1A messenger ribonucleic acid in the carbamazepine group was higher than that in the control group, but the difference was not statistically significant (p>0.05). The level of SCN1A protein product Nav1.1 in the model group was significantly higher than that in the control group and the carbamazepine group, and the difference was statistically significant, although the level of SCN1A protein product Nav1.1 in the carbamazepine group was higher than that in the control group, but the difference was not statistically significant, indicating that the administration of carbamazepine could reduce the expression of CN1A protein product Nav1.1 level. Immuno-histochemical results showed that SCN1A was more expressed in the temporal cortex and CA1 and CA3 regions of the hippocampus in normal rats. Compared with the control group, the expression of SCN1A immuno positive cells in the hippocampal CA1 and CA3 regions and temporal cortex of the model group was increased, with highly significant difference (p<0.01); no significant difference (p>0.05) was found in the carbamazepine group. Carbamazepine could better control the abnormally elevated expression of SCN1A in temporal lobe epileptic rats and return its expression level to normal, which may be related to the restoration of the impaired inward rectification by reducing the expression of Nav1.1 channel protein and thus buffering the extracellular sodium load to some extent. Maintaining resting membrane potential reduces neuronal excitability ultimately may reduce the generation of epileptiform discharges.