Scorpion Venom Upregulated GDNF MRNA Expression In Hippocampus In Lithium Chloride-pilocarpine Induced Rat Status Epileptics Model

Objective:（1）Investigation the effect of SV and VPA onneurobehavioral and seizures in lithium chloride-pilocarpine inducedstatus epileptics（Li-Pilo SE） model rat.（2） To observe the expression ofglial cell line-derived neurotrophic factor（GDNF） mRNA inhippocampus after lithium-pilocarpine induced SE on male adult ratsafter the intervention of SV and explore the possible anti-epilepticmechanism. Methods:（1）98SD rats were enrolled into group （normalcontrol group,n=6） and group （SV control group,n=6），The remaining86rats were modeling, Li-Pilo SE successful firing of the64（four died）,ignite not the success of the22，four died, the success of the modeling rat60, All the Li-Pilo SE model rats were enrolled into three groupsrandomly:Epilepsy model only group, n=20),VPA treating group, n=20,SV treating group, n=20. Epilepsy model only group, VPA treating group,SV treating group were further divided into5subgroups based on thedifferent sacrifice time: at3thh,6thh,24thh,3thd and7thd after SE induction,4rats in each subgroup.（2） Epilepsy model was successful after15minutes, The Saline control group，model group with epilepsy wereintragastric administrated with normal sodium; the Control group ofscorpion venom, scorpion venom in the intervention group were givenSV(0.3mg·kg^-1·d^-1); the valproic acid in the intervention group wasadministrated with VPA(120mg·kg^-1·d^-1). The behaviors, death status,seizure frequency and severity scale seizure of the rats were monitoredwithin7days after intervention;（3） The expression of GDNFmRNA in rat hippocampus were detected by In situ hybridization （ISH） at3^thh,6^thh,24^thd,3^thd,7thd after SE induction in each group. And then, to analyze thediscrepancy of these values in each group. Results:（1） Behavioralobservation results of the Li-Pilo SE model rats:①74.42%of the Li-Pilomodel rats was induced SE successfully; most of the rats in model groupseizured over grade Ⅲ～Ⅴ, and seizured frequently；With epilepsymodel group, the level of SV intervention group seizures decreasedsignificantly （P <0.05）, the onset of the total number of significantlyreduced （P <0.05）.（2） Dynamic changes of GDNF mRNA-positivecells（PC） in Li-Pilo SE model rats hippocampus after intervention in eachgroup:①The number ofGDNF mRNA-PC in the rat hippocampusshowed a small amount of expression in saline control group and SVcontrol group, but no significant differences between the two （P>0.05）;②T he3h epilepsy model group, the SV in the intervention group and theVPA intervention group of GDNF mRNA-positive cells number ofexpression than the control group showed an increasing tendency, but didnot reach statistically significant differences between the groups was nosignificant difference （P>0.05）; The6h SV,VPA intervention groupand VPA in the intervention group of GDNF mRNA positive cells in theexpression in hippocampus CA1,CA3regions,a significant increasecompared to the epilepsy model group （P <0.05）; Three groups ofGDNF mRNA positive cells in the expression in hippocampus DGregions,a significant increase,Between the groups statistically nodifference（P>0.05）,24h, SV of VPA in the intervention group of GDNFmRNA-positive cell number gradually reduced, but still higher than theepilepsy model group, the two groups with epilepsy model group difference was statistically significant （P <0.05）.Observation3d and7d,the SV of VPA in the intervention group rat hippocampal GDNF mRNAexpression of the number of positive cells in the districts graduallyreduced, the difference not statistically significant （P>0.05）, in whichepilepsy model group reached the peak at3d. Conclusion:（1）SV hassignificant anti-epileptic effects on Li-Pilo SE rats;（2）Li-Pilo SE ratmodel of After SV,VPA intervention, GDNF mRNA-positive cell countover time dynamic changes in expression in the rat hippocampus: Theincrease began at3h,6h reached the peak around, since the expressionof the rendering down. Epilepsy model group to express the volume ofthe peak in the3d,Delay compared with the peak time of the VPA, theSV in the intervention group, The results of in the Li-Pilo SE model,the SV,VPA has a significant effect of brain protection may both play animportant antiepileptic effect one of the mechanisms.