Neuroprotective Effects Of Topiramate And Valproate On Immature Rat With Seizure-induced Brain Damage

[Objective]To explore the neuroprotective of seizure-induced cerebral damage in immature rats with topiramate(TPM) , valproate(VPA) and combine the two,which may provide the experimental basis for ration administration.[Methods]Sixty 3 or 4 week-old male Wistar rats were randomly divided into 5 groups of 12 rats each. The groups (Groups B-E ) were rat model of epilepsy, induced by Pentylenetetrazol (PTZ).The rats in three experimental groups were administered intragastrically with TPM 40 mg/(kg.d), VPA 200 mg/(kg.d) and TPM 40 mg/(kg.d)+ VPA 200 mg/(kg.d), two control groups(Groups A and B )with the equal amount of distilled water administration. After 2-month administration , the changes of body weigth, the behavior of the rats were observed, the levels of serum neuron- specific enolase(NSE) of blood serum, and the ultrastructural change of the hippocampus were oberved under the electron microscope.[Result]1. Effect on body weight of the immatrue rats with epilepsyThe body weight gain of rats in group A and B had no difference . TPM reduced the body weight gain of rat(P<0.05),VPA raised the body weight gain of rat(P<0.05), and there were no difference between the group E and C(P>0.05).2. EthologyGroup A had no behavior abnormality. Group B appeared class 2~4 by denom Racine and duration time were long. Compare with group B,TPM and VPA delayed the latent period, the duration time were shorten (P<0.05). but the duration time in group E were longer(P<0.05).3. The level of NSE in blood serumIt was significantly heightened in group B than in the normal group(P<0.01). Compare with group B, the group TPM and VPA were lower (P<0.05), but there was no significantly low in group TPM+VPA(P>0.05).4.The pathologic change of the hippocampus4.1 Light microscope: The neuron in the hippocampus of group A was normal. In group B, the hippocampus appeared necrotic neuron. The damage neuron in TPM group and VPA group had lessened. But the group TPM+VPA had little improved.4.2 Electron microscopy: The ultrastructural of the hippocampus were fundamentally normal. We found the mitochondrial ultrastructure were seriously damage in group B. But the damage degree of the TPM group and the VPA group were lower. The group TPM+VPA also had little improved.[Conclusions]Continuous administration of these two anti-epilepsy drugs was found to be effective in protection of brain damage. But combined this two drugs may weaken this effect.