Effect of MK-801 on Neuronal Cell Loss and Fos Expression of Hippocampus in Lithium-Pilocarpine Induced Status Epilepticus / 대한간질학회지

ABSTRACT

BACKGROUND & OBJECTIVES: Endogenous excitatory amino acid has been implicated in neuronal damages occurred neurotransmitter in the CNS, Exerts its neurotoxic activity primarily by binding to the NMDA receptor, one of the three glutamate receptors, We evaluated the effect of MK-801, a non-competitive NMDA receptor antagonist, on both Fos expression and neuronal damages in lithium-pilocarpine induced status epilepticus rat model. METHODS: Seizured was induced in rats by lithum pretreatment followed by low dose of pilocarpine (30 mg/kg, ip). MK-801 (1 mg/kg) was treated 15 min before (MK-801 Pre group, N=5) or 20 min after the injection of pilocarpine (MK-801 Post group, N-5). Saline, instead of MK-801, was injected for the Control group (N=5). RESULTS: Seizure-induced neuronal damages, which was evaluated by the counting of the number of viable pyramidal cells in the area of CA1 and CA3 of the hippocampus, were significantly inhibited by MK-801 in both MK-801 Pre and Post groups. This protective effect of MK-801 was observed only in the CA1 area and was not typical in the CA3 area in both groups, and there was no differences in MK-801 activity between Pre and Post group. We also examined the expression of Fos, which has been known to be involved in long-term neuronal plasticty or delayed neuronal insults, by the immunohistochemical analysis in the hippocampus and thalamus. Pilocarpine induced Fos expression significantly in the Control group and moderately in the MK-801 Post groups, whereas, it was completely blocked by the pretreatment of MK-801 in hippocampus. CONCLUSION: Our results showed that MK-801 prevented the hippicampal cells from neuronal damages as well as inhibited Fos expression in the pilocarpine-induced rat seizure models. These results suggest the roles of NMDA receptor and Fos protein in seizure-related hippicampal damages.