Reseach Of Safety Of Topiramate On Pedo-Epilepsy

ObjectiveEpilepsy is a common chronic disease of nervous system .There are 5 hundreds thousands epilepsy sufferers, 75% of which can gain control of attack with antiepileptic drugs (AEDs). AEDs educe action with voltage dependent iron channel, enhancing the inhibiting affection effect of GABA ,inhibiting excitability amino acids neurotransmitter(NT). Topiramate (TMP) is a new, broad-spectrum antiepileptic drugs,which has more than six contribution mechanisms .It has been more and more accredit that it has nerve conservation effect. However,which is paid more attention to is the effect on cognition .Cognition is the ability of deal information precisely , and to make adequate reaction and behavior ,which is accommodated by central nerves system(CNS).The function of central nerves system depends on the brain development normally .The development of CNS has close connection with neurogenesis and neurotrophic factors .In this study, the mechanism of TMP on developmental brain has been discussed on the level of cell and molecule.MethodsThe young rats of 1 day were randomly divided into 3 groups :â… group (neurogenesis group);â…¡group (mossy fiber sprouting group);â…¢group(BDNF,NT3mRNA group) .â… ,â…¡andâ…¢groups were respectively divided into 3 groups dependent on the intervention time of anti-epilepsy drugs,P7,P14,P21,each group was divided into 5groups,A group (low dosage of TMP),B group (high dosage of TMP);C group (Sodium Valproate intervention group , VPA group);D group (model control group) and E group (normal control group). There are 45 groups of all, 5 rats in every group.Rats except the normal control group (E group) were received intraperitoneal injection of 3-8 mg/kg kainic acid(KA) to induce seizures, and normal control rats were injected with the same dose of sodium chloride .This dosage can induce rats to epileptic state or spontaneous recurrent seizure (SRS). Since 7 days after birth, A,B,C,D groups were received TMP 40mg/kg,TMP 80mg/kg, valproate sodium 50mg/kg,and distilled water 50mg/kg respectively per day ,until the day before the end day.Use Brdu mark new cell ,immunohistochemistry ,and Timm's staining to show the impaction of anti-epilepsy drugs on neurogenesis and mossy fiber sprouting of different dosages .Use RT-PCR technology to detect the impaction of anti-epilepsy drugs on BDNF and NT3mRNA of different dosage.ResultsNot only topiramate but also valproate sodium can inhibit convulsion efficiently.(1) Neurogenesis :AEDs can induce neurogenesis in adult rats ,but inhibit neurogenesis in developing brain .There are less nerogenesis in both VPA group and TMP group (both low dosage of TMP and high dosage of TMP),while there are more less neurogenesis in model control group.(2) Mossy fiber sprouting :There are mossy fiber sprouting in model control group (D group),while there are not conspicuous mossy fiber sprouting in both VPA group(C group) and TMP group(A,B group).(3)BDNF,NT-3: There are less synthesis of BDNF and NT-3 in both model control group(D group) and high dosage of TMP (B group),and there are not noticeable differences between these two groups .There are more less synthesis of BDNF and NT-3 in VPA group(C group)and low dosage of TMP(A group).Conclusion(1) Different anti-epileptic drugs have different influences on developing brain with epilesy attack.(2)TMP has no toxic effect on developing brain ,but has effect of preventing damage on newborn rodents brain.(3)TMP is safe on treating pedo-epilepsy.