| Objective To study the effects of Beta amyloid protein(A?)on the progress of epilepsy(EP).To explore the association between increased susceptibility of EP and pathological changes of Alzheimer's disease(AD)from the perspective of disease pathogenesis.Methods 40 male Wistar rats were randomly divided into Beta amyloid protein 1-42(A?1-42)+ pilocarpine(PILO)group,A?1-42 group,Phosphate buffer solution(PBS)+PILO group and PBS group,10 rats in each group.A?1-42 was injected into the hippocampal CA3 region of Wistar rats,and the Morris water maze test was observed after 2 weeks.Escape latency,the percentage of swimming time in the target quadrant and the number of times of crossing the platform were recorded.The statistical analysis software was used to detect whether the rat AD model is successful.After the model was successfully made,the rat model of chronic EP was established by intraperitoneal injection of LI-PILO.The latency of EP(time required to reach grade IV and above),degree of seizure and mortality were recorded according to Racine grading criteria.The mossy fiber sprouting(MFS)level of dentate gyrus(DG)in hippocampus was observed by modified Timm's staining.Results Preparation of rat AD model:The one rat died in each AD model group and the PBS control group after injection of A?1-42.The anatomical findings showed no obvious cause of death.It was presumed that the possible cause of death was that there were individual differences between rats.The results of Morris water maze test showed that the escape latency between the AD model group and the PBS group was significantly prolonged(P <0.01).The proportion of swimming time in the target quadrant was shortened(P <0.05),and the number of crossing the platform was also significantly reduced P <0.05).It indicated that the AD model was successfully prepared.Preparation of rat EP model:According to Racine grading criteria,the latency of EP in A?1-42 + PILO group was significantly shorter(P <0.01)and the degree of seizure was more severe(P<0.05)then PBS + PILO group.The mortality of rat in A?1-42 + PILO group was significantly increased compared with PBS + PILO group(P =0.0294)and PBS group(P=0.0108).The histopathology experiment of rat brain:The MFS staining of hippocampal DG was obviously stronger in A?1-42 + PILO group then that in the PBS + PILO(P <0.05)group,by modified Timm's staining showed.In A?1-42 group,the MFS staining of hippocampal DG was also obviously increased.There was no significant difference compared with PBS + PILO group(P> 0.05).There was significant difference in the intensity of MFS staining between PBS + PILO group and PBS group(P <0.01).The intensity of MFS staining in A?1-42 group and PBS group was also significantly increased(P <0.01).Conclusion The injection of A?1-42 in hippocampal CA3 region can lead to the impaired hippocampus –related learning and memory function in rats.It was further confirmed that the Morris water maze test which verified the above-mentioned dysfunction proves that A? can induce the change of dementia behavior.The existing of A? increasingly induces the susceptibility of rats in the EP,which indicates that A? plays a facilitation role of in the occurrence of EP.From the pathology of disease,it is clear that AD is closely related to EP.Through histochemical staining,high intensity MFS staining of hippocampal DG in A?1-42 + PILO group was found to further confirm that the structural basis of A? inducing the susceptibility of rats in the EP may be associated with the significant increase in MFS levels by virtue of the pathophysiological mechanisms.Though the EP was not found in A?1-42 group,MFS staining was also enhanced in the hippocampus DG of rats,indicating that MFS was not a consequence of seizures,but rather represents an intrinsically abnormal network connectivity in these rats.In the “two hit”theory of EP,the potential mechanism of function of A? leads to the first brain damage.Significant correlation exists between the increase in the susceptibility of EP and the pathogenesis of AD. |
PDF Full Text Request