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Influence Of Lamotrigine On Cognition And Multidrug Resistance Gene Expression In The Hippocampus Of Spontaneous Epileptic Rats

Posted on:2009-07-09Degree:MasterType:Thesis
Country:ChinaCandidate:D Q ZhangFull Text:PDF
GTID:2144360245995495Subject:Academy of Pediatrics
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ObjectiveEpilepsy is a common chronic disease of nervous system.Some epilepsy patients have impaired cognitive abilities.Many scholars hold that the antiepileptic drugs may contribute to this impairment.With the widely clinical usage of lamotrigine,the effect of lamotrigine on connitive has attracted more and more attention.In this study,an immature murine model of chronic spontaneous temporal epilepsy,which is attributed to statural epilepticus induced by kainic acid,was used to investigate the chronic effect of lamotrigine on spatial learning and memory.MethodsThe number of 65 male young rats of 7 days old were randomly divided into experimental group and control group.Rats in the experimental group were received intraperitoneal injection of 1 mg/kg kainic acid to induce seizures,and control rats were injected with the same dose of sodium chloride.According to Lado standard classification of seizures,those young rats whose seizure degree were beyond five and became status epilepticus after intraperitoneal injection were used as successful seizure models if they caught the spontaneous seizures after two weeks.When spontaneous seizures were developed,the 26 survived epileptic rats were divided into EP group and EP+LTG group.Rats of control group were divided into NS group and NS+LTG group.Rats of EP+LTG group and NS+LTG group were treated with therapeutic dose of lamotrigine after the spontaneous seizures developed for a week.Spontaneous recurrent seizures were recorded everyday.Spatial learning and memory ability was evaluated by Morris water maze after 5 weeks drug treatment.ResultsIn KA group,the rats received intraperitoneal injection of kainic acid suffered from epileptic seizure after 2-10 min injection.The latent time was average 4.3±3.1min.Five rats died whin eight hours and two rats died after 24 hours.In control group,no rats suffered from seizures or died.Rats of KA group gradually developed spontaneous recurrent seizure (SRS)2 weeks after kainic acid injection.During the last week of Lamotrigine treatment,in EP group,the mean times of SRS was 5.94±1.53. In EP+LTG group,two rats did not suffer from SRS,and the mean times of SRS was 2.18±1.16.There was significant difference between the two groups(P<0.05).In the test of Morris water maze,the EP group spent the most time in finding the platform but the shortest time in the target quadrant. Compared with the EP group,EP+LTG group spent less time in finding the platform and the more time in the target quadrant(P<0.05).LTG had no effect on water maze performance to rats without KA induction.ConclusionLTG can control the spontaneous recurrent seizure of spontaneous epileptic immature rats perfectly.For developing epileptic rat brain, LTG can improve the ability of Spatial Learning and Memory. ObjectiveAbout 25%of patients with epilepsy suffer from intractable seizures,which cannot be properly controlled by antiepileptic drugs. Overexpression of multidrug resistance gene and p-glycoprotein is thought to have close relationship with Refractory Epilepsy. Recently,many scholars used the murine model of status epilepicus to study the multipledrug resistant gene,nevertheless,some research showed that the production and maintenance of epilepsy is not similar in different periods of ontogeny.In this study,childhood rat model of spontaneous seizures induced by kainic acid was used to explore whether the new antiepileptic drug-lamotrigine affects the expression of mdr1a,mdr1b and P-Glycoprotein(P-gp)in the hippocampus of spontaneous seizures rat.MethodsThe number of 65 male young rats of 7 days old were randomly divided into experimental group and control group.Rats in the experimental group were received intraperitoneal injection of 1 mg/kg kainic acid to induce seizures,and control rats were injected with the same dose of sodium chloride.According to Lado standard classification of seizures,those young rats whose seizure degree were beyond five and became status epilepticus after intraperitoneal injection were used as successful seizure models if they caught the spontaneous seizures after two weeks.When spontaneous seizures were developed,the 26 survived epileptic rats were divided into EP group and EP+LTG group.Rats of control group were divided into NS group and NS+LTG group.Rats of EP+LTG group and NS+LTG group were treated with therapeutic dose of lamotrigine after the spontaneous seizures developed for a week.All rats were killed at the 42th day of administration.Mdr1a and mdr1b mRNA in the hippocampus was measured by RT-PCR.ResultsCompared with the control groups,expression of mdr1a and mdr1b mRNA in the hippocampus increased significantly in EP and EP+LTG group(P<0.001)Mdr1a and mdr1b mRNA expression level of EP+LTG group was higher than that of EP group,and NS+LTG group higher than NS group,but there was no statistical difference(P>0.05).ConclusionFrequent seizures results inoverexpression of mdr1a,mdr1b mRNA in the hippocampus.Lamotrigine dose not enhance the expression of mdr1a,mdr1b mRNA in the hippocampus.
Keywords/Search Tags:Cognition, Epilepsy, Antiepileptic drugs, Rat, Multidrug resistance gene, hippocampus
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