Effects Of Levetiracetam On Expression Of NCAM And GAP-43mRNA In Hippocampus Of Rats With Epilepsy

Epilepsy is the most common neurological disease in children.It is a major cause of child disability. The main treatment is drug and its control rate is about 75%, but still 20% -30% of epilepsy is difficult to control and becomes intractable epilepsy. In recent years, research on the pathogenesis of epilepsy becomes an important topic in the medical field. The research has already been focus on synaptic plasticity,ion channel,neurotransmitter and glial cells and so on.The relation between synaptic plasticity and epileptogenesis has been paid much attentions.Nerve cell adhesion molecule (NCAM) is a member of immunoglobulin family, which is mainly expressed in the nervous system.It participates neural cell adhesion, promotes axonal growth, neuronal migration and the formation of neuronal loop, affects the process of synaptic plasticity.Growth associated protein -43 (GAP-43) is distributed in the nerve-specific membrane protein phosphorylation.It plays a key role in guiding axonal growth, synaptic regulation in the reconstruction process. NCAM and GAP-43 are closely related to the development and migration of nerve cell,which are the major molecular markers for studying synaptic plasticity.Levetiracetam (LEV) is a new antiepileptic drug.Its mechanism is extremely complex, and one is synaptic plasticity,but is paid to relatively little attention. The experiment established a rat model of epilepsy, used LEV to intervene,observed the expression of GAP-43 and NCAM mRNA in the rat hippocampus, in order to further clarify the antiepileptic mechanism of LEV and provide experimental evidence for dose effect.ObjectiveTo explore the effects of Levetiracetam (LEV) on the expression of nerve Cell Adhesion molecule(NCAM) and growth-associated protein 43 (GAP-43) mRNA in the hippocampus of epilepsy Rats induced by lithium- pilocarpine(Li-PILO),and provide an experimental base and a theoretical foudation for investigating the antiepileptic mechanism of LEV and its dose-response.Materials and MethodsForty-eight rats were radomly divided into normal control group, lithium-pilocarpine(Li-PILO)group,150mg/Kg LEVgroup, and 300mg/Kg LEV group (n=12).The models of rats with epilepsy treated by LEV were established. The behavior of Rats Was observed, and the expression of NCAM and GAP-43mRNA in hippocampus of rats was determined by Real-time PCR.Results1 Behavior observation in ratsa)6 rats failed to induce SE,the success rate is 83.3%b) the model group occured SE in about 30 minutesc) Induced after 2-5days, the model group rats had crouched motionless, extreme irritability. Then observed the spontaneousâ… -â…¢grade recurrence. After the LEV was given, only four appeared Gradeâ… -â…¢seizures. The control group was no change.2 NCAM and GAP-43 mRNA expression in hippocampus of ratsThe expression of NCAM and GAP-43 mRNA in Li- PILO group is significantly higher than that in control group (P< 0.05). The expression in 150 and 300mg/kg LEV Groups is higher than that in control group (P<0.05),while significantly lower than that in Li-PILO group (P< 0.05), and that in 300 mg/kg LEV group is lower than that in 150 mg/kg LEV group(P<0.05).Conclusions 1.LEV can inhibit the overexpression of NCAM and GAP-43 to inhibit neuronal synaptic reorganization in the epilepsy model.2.When the dose of LEV achieves a certain degree, the inhibitory effect to NCAM and GAP-43mRNA in hippocampus is related with the dose of LEV.