The Effects Of Cognition And Apoptotic Neurons And The Expression Of Bcl-2 And Bax In The Hippocampus After Epileptic Rats' Treated With Valproate Or Topiramate

Objective Epilepsy is a common chronic dysencephalia syndromes induced by some diseases. The cognitive handicap after epilepsy have received attentions, although the mechanisms are not well known, the effective methods haven't been found to prevent and cure it. How the antiepileptic drugs (AEDs) effect cognitive are unknown. To explore the effect of valproate and topiramate on rats'cognitive function, use the Morris water maze we observe the animal epilepsy model changes of ethology, the ability of memory and learning, use terminal deoxynucleotidyl transferse-mediated biotinylated deoxyuridine triphosphate nickel end labeling (TUNEL) to detect apoptotic neurons in hippocampus, use Cytochemistry to display Bcl-2 and Bax positive neurons distribution in hippocampus.Method1 Divide into four groups randomly40 minimal disease adolescent male health Sprague-Dawley (SD) rats, weighing (201+29)g, were randomly divided into four groups: normal control group (NS group), status epilepticus group (Pentylenetetrazole, PTZ group), valproate group (VPA group), topiramate group (TPM group).2 Model makingAll the rats except those in NS group were administrated initially 35mg/kg of PTZ solution by peritoneal cavity route every day, NS group were administrated the same times and dose of normal saline with the same method. This work was lasted almost two weeks.3 ElectroencephalogramUse the stereotaxic apparatus to make the animals keep still, then record its EEG.4 Treated with ADEsWhen the model were successfully made, the rats in VPA group were treated with VPA (250mg/(kg·d),twice one day), the rats in TPM group were treated with TPM (80mg/(kg·d), twice one day). The other two groups were treated with normal saline in the same method. Rats of all the four groups were subjected to Morris water maze test after had been treated two weeks later.5 Praxiology detectingUse the Morris water maze test to detect the rats'ability of memory and studying after them treated by AEDs two weeks later.6 Detect the apoptotic neurons in hippocampusTerminal deoxynucleotidyl transferse-mediated biotinylated deoxyuridine triphosphate nickel end labeling (TUNEL)After Morris water maze test, the rats of each group were deeply narcosised before instillation. Detached middle hippocampus soked in 4% formaldehydum polymerisatum. Display the apoptotic neurons using the method according to TUNEL.7 CytochemistryAfter Morris water maze test, the rats of each group were deeply narcosised before instillation. Detached middle hippocampus soked in 4% formaldehydum polymerisatum. Then display the Bcl-2 and Bax positive neurons .Result1 Seizure conditions of modal rats All the rats except those in NS group had epileptic attacks in higher or lower degree, proving that the method to make epileptic rats are successfully.2 EEGIn NS group EEG present a rhythm of 9-11 Hz low and middle amplitudeαwave .In other three groups EEG present obviously epileptic electric discharges including spike wave , sharp wave , spine-slow combining wave, sharp -slow combining wave.3 Treatment resultVPA and TPM can control the epileptic rats attack. 4 Water maze test resultThe performance record of VPA group has been elevated quickly (P<0.01). The performance record of TPM group has been elevated slowly (P>0.05),and was worse than NS group. The total time TPM was longer than other groups in six times every day (P<0.01). The time of TPM group was prolonged than other groups in searching for platform quadrant (P<0.01). No difference in other 3 groups.5.TUNEL demonstrated that there were little apoptotic neurons in hippocampus of NS group, PTZ group and VPA group. The number of apoptotic neurons in hippocampus of TPM group was larger than other 3 groups.6.Cytochemistry demonstrated that there was little of Bcl-2 positive neurons in hippocampus of NS group, there was a large number of Bcl-2 positive neurons in hippocampus of PTZ group, there was the same number of Bcl-2 positive neurons in hippocampus of VPA group and the PTZ group, and the number of Bcl-2 positive neurons in hippocampus of TPM group is smaller than the PTZ group.7.Cytochemistry demonstrated that there was little of Bax positive neurons in hippocampus of NS group, there was a large number of Bax positive neurons in hippocampus of PTZ group, the number of Bax positive neurons in hippocampus of VPA group is smaller than the PTZ group, and the number of Bax positive neurons in hippocampus of TPM group is larger than the PTZ group.Conclusion1.Successfully established chronic epilepticus animal model using PTZ.2.Morris water maze can be used to detect rats'cognition ability.3.TPM may damage epileptic rats'cognition function, while VPA may not damage this function.4.The dysfunction of cognition may have a relationship with the increase of apoptotic neurons in hippocampus of epileptic rat.5.The increase of apoptotic neurons in hippocampus of epileptic rat may have a relationship with the decrease of Bcl-2 positive neurons and the increase of Bax positive neurons.