Lamotrigine: neuroprotective effect in rats after kainic acid induced seizures

Purpose: Kainic acid (KA) is used as an experimental agent which produces convulsions and neurotoxic lesions. We examined the effects of KA induced convulsions on the activity of Na+, K+- ATPase, activation of JNK/c-jun axis and histological changes in rat hippocampus. Lamotrigine (LTG) is an antiepileptic drug, a glutamate release inhibitor, with action at the neuronal voltage-gated sodium channel. Therefore, this study was also designed to investigate the influence of LTG pre-treatment on the mentioned hippocampal changes. Methods: The study was carried out on Hanover-Wistar rats. Na+, K+- ATPase activity from hippocampal tissue was determined two hours, three days and five days after a single subcutaneous KA (8 mg/kg) injection. The inductions of JNK/c-jun and hippocampal histological changes were determined two hours and five days after KA application. LTG (30 mg/kg i.p.) was used two hours before KA application and for five consecutive days. Results: After KA application, Na+, K+- ATPase activity was significantly inhibited and the induction of JNK/c-jun axis was observed. The number of hippocampal CA1 cells was significantly lower in all groups of the rats treated with KA. In the group of LTG pre-treated rats Na+, K+- ATPase inhibition, and JNK/c-jun induction were detected the fifth day after KA treatment, but the inhibition of Na+, K+- ATPase was significantly less pronounced. The number of damaged cells was significantly less in LTG pre-treated rats. Conclusion: Systemic application of KA showed statistically significant changes in the evaluated parameters in the rats' hippocampi. LTG pre-treatment has a partially neuroprotective effect in KA-treated animals.