Rapamycin Modulates Cognition And Spontaneous Epilepsy In Midlife Rats With Malformations Of Cortical Development

Objective : To observe the rapamycin modulates cognition and spontaneous epilepsy in midlife rats with malformations of cortical development,explore whether rapamycin has a protect effect on MCD rats,thus for the medication treatment research of resistant epilepsy provide a new research direction.Methods: X-ray irradiated pregnant-17-day rats,the F1 generation selected for MCD model rats,the F1 generation of healthy pregnant rats selected as normal control group,two groups of rats respectively raised to51 weeks(midlife),then each group were divided into rapamycin group,solvent group and normal saline group,intraperitoneal injection of above drug for 30 days,respectively.Rats in each group before and after drug injection carried on Morris water maze,testing the escape latencies,target quadrant time ratio and the number of through the platform,for determining whether their learning and memory ability changed.Then monitored EEG and counted the frequency of epileptiform wave in each group both bilateral cerebral hemisphere.Finally fixed perfusion all rats,removed the brain tissue,measured their weight,volume and each radial diameter of the rat brain,paraffin section,HE staining.Video monitoring for three months,including before,during and after drug injection,selected 8 days of each stages for artificial observation of the spontaneous seizures.Results:(1)Morris water maze-the average escape latencies: Model groups and normal groups showed obvious difference inescape latency before drug injection.Compairing with any group in normal groups,that in model groups showed significant differences.In model groups,There was no statistical difference between groups corresponding to the number of days before and after injection.Morris water maze-the target quadrant time ratio and the number of through the platform: Rapamycin group in model groups showed obvious difference with the rapamycin group in normal groups.In model groups,There was no statistical difference between groups corresponding to the number of days before and after incubation.(2)Electroencephalogram: The corresponding parts(frontal,parietal lobe and hippocampus)of bilateral cerebral hemisphere discharged at the same time.Normal groups showd average frequency of epileptiform wave per minute significantly lower than the model groups,among model groups average frequency of epileptiform waves were rapamycin group< solvent group <normal saline group.Compared with solvent group and normal saline group,rapamycin group have statistical significance respectively.(3)Long-range video monitoring: Both normal groups and model groups were not observed spontaneous seizures.(4)Gross specimen and pathology: Brain tissue volume,weight and each radial diameter were reduced in model groups,the difference was statistically significant.Normal group rats of cortex structure clear and layered,cell ordered,no abnormal neurons.rapamycin group in model group appeared missing corpus callosum,lateral ventricle enlargement,cortex structure disorder,neuronal polarity disorder,uneven density,visible abnormalneurons,nodules are visible in hippocampal CA1 area.Conclusion:(1),195 cGy X-ray irradiated pregnant-17-day rats,the F1 generation selected for MCD model rats successful,this method is simple and reliable.(2),rapamycin may reduce midlife MCD rats incidence of epileptiform wave.(3),rapamycin did not obviously improve learning and memory ability in midlife MCD model rats,and can not reverse the pathological damage in the brain.