The Impact Of Rapamycin On The Brain Developme Nt Of Cerebral Cortex Developmental Disorders Embryonic Rat And The Analysis Of Its Cerebral Cortex

Objective:To invesgate whether the specific inhibitor of mammalian rapamycin protein(mTOR)rapamycin could prevent the progress of cerebral cortex developmental disorder caused by x-ray irradiation in uterus of embryonic rat.This study could supply the experimental basis of mTOR targeting s ignal path on the treatment of epilepsy induced by DCDs,furthermore,it could offer the clinical evidence for intractable epilepsy(IE)therapy.Methods:(1).Twelve healthy pregnant SD rats were randomly divided into four groups: Normal group,Model group(SD rats model after x-ray irradiation),Solvent group(DMSO was employed in SD rats model)and Rapamycin group(Rapamycin was applied in SD rats model).On the 16 th day of pregnancy,Solvent group and Rapamycin group were disposed with DMSO intraperitoneal injected and Rapamycin intraperitoneal injected respectively.On the 17 th day,excluding Normal group,other groups were disposed with x-ray irradiation(195c GY).The fetal rats were the subjects of the experiment.(2)We desposed One pregnant rat at 18 th day,20 th day and 22 th day from each group respectively,then get off the brain tissue of the fetal rats and fix it with 4% formalin for 3 days.Thenwe employed paraffin embedding and serial section.Paraffin sections were s lice to 5 ?m and get one section every 50 ? m.HE staining and Nissl staining was used to observe the pathological characteristics of cerebral cortex structure and hippocampal formation.(3).Take photos of HE and Nissl staining image from the view of prefrontal cortex,hippocampal cortex and hippocampus,then measurement and comparison of the thickness of motor cortex and sensory area cerebral cortex among each group.Results:(1)HE staining: The comparison between model group and Normal group showed that the cortex of model group became thinner,the callosum was partly defic iency,the cortex structure was disorder,the boundary was unclear,the hippocampal structure was abnormal.Compared with Normal group,the Solvent group shows the similar abnormal pathological structure,The Rapamycin group showed partly similar pathological structure changed compared with Normal group but not serious as Normal group and Model group.(2).Nissl staining: Compared with the Normal group,the Model group shows that the cortex became thinner,the callosum was disappeared,the cortex structure became disorder,the hippocampal structure was abnormal and the other abnormal pathologic changes.Solvent group has similar pathological structure with Model group.The Rapamycin group showed the part of pathological structure compared with Normal group but the severity of pathological structure change was much less than Model group and Solvent group.3.The analys is of the thickness of cerebral cortex:The difference is not statistically significant in each group(E18)(P>0.05).compared with the Normal group,the Model group shows that the thickness of the prefrontal cortex motor area,sensory area and hippocampal cortex motor area,sensory area were decreased significantly(P<0.05),The difference is not statistically s ignificant when compared Solvent group with Model group(P>0.05)(E20 and E22).There was no significantly differences between Rapamycin group and Normal group(P>0.05).When compared with Rapamyc in group,the thickness of cortex was decreased in Model group(P<0.05).The thickness of cortex in Stereological analys is was decreased in Solvent group when compared with Rapamycin group(P<0.05).Conclusion:(1).x-ray irradiation on 17 days pregnant rat induce the late stage embryonic cortex developmental disorder.(2).Rapamycin could prevent the 17 day-pregnant cerebral cortex disorder induced by the x-ray.(3).The cortical thickness testing reveals that the decreased of cortex thickness is the essence of brain atrophy.