The effects of lamotrigine and ethosuximide on seizure frequency, neuronal loss, and astrogliosis in a model of temporal-lobe epilepsy.

Objective: The putative neuroprotective and disease-modifying effects of lamotrigine (LTG) and ethosuximide (ESM) were investigated in the lithium-pilocarpine (Li-Pc) model of temporal-lobe epilepsy (TLE) in rats. Then, spontaneous recurrent seizures (SRS), neuronal loss and astrogliosis were assessed.

Methods: Status Epilepticus (SE) was induced by Li-Pc in five experimental groups: 24 h after SE, all rats received twice daily either a low (10 mg/kg) or high (20 mg/kg) dose of LTG, or a low (25 mg/kg) or high (50 mg/kg) dose of ESM, or solvent. The sixth group (control) did not receive Li-Pc and was given twice daily injections with solvent only. Drug administration lasted for 7 d. Rats were systematically observed in the 5th and 6th weeks, after that the brains were prepared for histology.

Results: LTG dose-dependently decreased the frequency of SRS, and restricted neuronal loss, as well as astrogliosis in the hippocampus compared with the untreated SE control group. However, ESM had none of the above-mentioned effects.

Conclusion: LTG had protective as well as disease-modifying effects in this TLE model. It was revealed that the disease-modifying effects were accompanied by the prevention of neuronal loss and astrogliosis. ESM was devoid of antiepileptogenic and its accompanying histological effects in this TLE model, in contrast to the antiepileptogenic effects found in the genetic absence epilepsy models, suggesting that different mechanisms are involved in the different models for epileptogenesis and antiepileptogenesis.