Abstract：OBJECTIVE: This study explored 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 rats with epilepsy induced by lithium-pilocarpine (Li-PILO) in order to provide a basis for investigating the antiepileptic mechanism of LEV and its doseresponse. METHODS: Forty-eight Wistar rats were randomly divided into a normal control, a Li-PILO model and two LEV treatment groups (LEV: 150 and 300 mg/kg) (n=12 each). The LEV treatment groups received LEV by intragastric administration 6 hrs after status epilepticus (once daily for 2 two weeks). The expressions of NCAM and GAP-43 mRNA in the hippocampus was determined by real-time PCR. RESULTS: The expression of NCAM and GAP-43 mRNA in the Li-PILO model group was significantly higher than in the normal control group (P<0.05). LEV treatment of 150 and 300 mg/kg significantly decreased the expression of NCAM and GAP-43 mRNA compared with the Li-PILO model group (P<0.05). The LEV treatment group at the dose of 300 mg/kg showed significantly lower expression of NCAM and GAP-43 mRNA than the 150 mg/kg LEV treatment group (P<0.05). CONCLUSIONS: Li-PILO can up-regulate the expressions of NCAM and GAP-43 mRNA in the hippocampus of rats with epilepsy. LEV can inhibit the expression of NCAM and GAP-43 mRNA and the effect is associated with the dose of LEV.
JIA Tian-Ming,LIU Tao,LUAN Bin et al. Effects of levetiracetam on the expression of NCAM and GAP-43 mRNA in the hippocampus of rats with epilepsy[J]. CJCP, 2011, 13(5): 428-431.
［1］Sato K, Iwai M, Nagano I, Shoji M, Abe K. Temporal and spacial changes of highly polysialylated neural cell adhesion molecule immunoreactivity in amygdala kindling development［J］. Neurolcal Res, 2003, 25 (1): 79-82.
［2］Longo B, Vezzani A, Mello LE. Growth-associated protein 43 expression in hippocampal molecular layer of chronic epileptic rats treated with cycloheximide［J］.Epilepsia, 2005, 46(Suppl 5):125-128.
［4］Bootsma HP, Ricker L, Diepman L, Gehring J, Hulsman J, Lambrechts D, et al. Levetiracetam in clinical practice: long-term experience in patients with refractory epilepsy referred to a tertiary epilepsy center［J］. Epilepsy Behav, 2007, 10 (2): 296-303.
［5］De Smedt T, Raedt R, Vonck K, Boon P. Levetiracetam: part II, the clinical profile of a novel anticonvulsant drug［J］. CNS Drug Rev,2007,13 (1): 57-78.
［6］De Smedt T, Raedt R, Vonck K, Boon P.Levetiracetam: the profile of a novel anticonvulsant drugpart I:preclinical data［J］. CNS Drug Rev, 2007, 13(l): 43-56.
［7］Racine RJ, Steingart M, Mclntyre DC. Development of kindling-prone and kindling-resistant rats:seleetive breeding and electrophysiological studies［J］. Epilepsy Res, 1999, 35(3): 183-195.
［8］Muller CJ, Bankstahl M, Groticke I, Loscher W. Pilocarpine vs. lithium-pilocarpine for induction of status epilepticus in mice: development of spontaneous seizures, beha-vioral aterations and neuronal damage［J］. Eur J Pharmacar, 2009, 619(1-3): 15-24.
［10］Racine RJ.Modification of seizure activity by electrical stimulation.Ⅱ.Motor seizure［J］. Electroencephalogr Clin Neurophysiol, 1972, 32(3): 281-294.
［11］Leite JP, Neder L, Arisi GM, Carlotti CG Jr, Assirati JA, Moreira JE. Plasticity, synaptic strength, and epilepsy: what can we learn from ultrastructural data?［J］. Epilepsia, 2005, 46 (Suppl 5): 134-141.
［12］Cavazos JE, Jones SM, Cross DJ. Sprouting and synaptic reorganization in the subiculum and CA1 region of the hippocampus in acute and chronic models of partialonset epilepsy［J］. Neuroscience, 2004, 126 (3): 677-688.
［14］Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam［J］. Proc Natl Acad Sci U S A, 2004, 101 (26): 9861-9866.
