Neuroprotective Properties Of Topiramate And Erythropoietin In The Rats With Epilepsy

[Objective] A new model of epilepsy was developed in rats after intervention ofTopiramate(TPM)and erythropoietin(EPO). Neuroprotective effects and thepossible mechanism of topiramate and erythropoietin were investigated inthis model.[Methods] Adult male Sprague-Dawley rats were randomized to five groups: normalcontrol group ,SE group, TPM50-SE group, TPM 100-SE group and EPO-SEgroup.After intervention with Topiramate (50 or 100 mg/kg.d) twice dailyfor five additional weeks or erythropoietin once, SE was induced in ratsof SE group, TPM50-SE group, TPM 100-SE group and EPO-SE group respectivelyby LiCl (3 mEq/kg) and pilocarpine (30 mg/kg). Normal control group wassubjected to Sodium Chloride instead.Rats were evaluated for visual-spatialmemory in the water maze, suspend tolerance in the suspension test beforeand after SE .Then caspase-3 immunohistochemistry was used to determinecaspase-3 expression and activation in frontal cortex and hippocampine. Cellapoptosis was examined by the flow cytometer and transmission electronmicroscope. All the results were analyzed on Statistical Package for SocialSciences 11.0.[Results] (1) All groups except the normol control group had been induced intoseizure ,and the severity or the mortality of seizure in those groups werenot different (P>0.05).(2) Apoptosis cells were observed in SE group and TPM50-SE group withthe transmission electron microscope,but no apoptosis had been found inother groups. (3) In the result of the flow cytometer, apoptosis rate of frontal cortexvaried from 0.4% to 9.9%. Normal control group was 0.4%,SE group was 9.9%,TPM50-SE group was 7.8%, TPM 100-SE group was 0.7% and EPO-SE group was 0.5%. (4) Corresponding to the high levels of neuron loss,The activated formof caspase-3 was most pronounced in SE group and TPM50-SE group. Theactivated form of caspase-3 in the hippocampal and prefrontal cortex of thetwo groups were significantly improved compared with the normal controlgroup(P<0.05). TPM 100-SE group and EPO-SE group had significant deviationwith the normal control group too(P<0.05),but they had even more differencewith SE group(P<0.01). In addition, the amount of activated caspase-3expression had a high positive correlation with apoptosis rate(r=0.955,rs=1.000). (5) The times of suspend tolerance in TPM50-SE group and TPM 100-SE groupwere much shorter than the normal control group before SE(P<0.05). Butboth of the two groups had reversed after SE (P>0.05). (6) In the water maze test, TPM50-SE group and TPM 100-SE group hadsignificant deviation with the normal control group before SE(P<0.05). Andthe visual-spatial memory of the TPM50-SE group remained worse than thenormal control group even after SE (P<0.05). (7) EPO-SE group had no difference with the normal control group in thewater maze test and suspend test, no matter before or after SE(P>0.05). (8) Compared with TPM50-SE group or TPM 100-SE group, EPO-SE group hadlower apoptosis rate and activated caspase-3 expression in the hippocampaland frontal cortex (P<0.05). [Conclusion] (1) TPM and EPO displayed neuroprotective properties in the hippocampaland frontal cortex of the rats following status epilepticus. (2) The neuroprotective action of TPM and EPO seems to be related totheir inhibitory effect on activated caspase-3 expression. (3) TPM and EPO were not sufficient to depress the severity or themortality of seizure. (4) TPM might impair the function and behavior of rats,but EPO wouldnot.