Intrahippocampal Injection Of Endothelin-1 Induces Seizures And Hippocampal Sclerosis In Mature Rats

Objective:The present study is designed to see whether intrahippocampal injection of endothelin (ET)-1 can induce seizures and hippocampal sclerosis.Method:Sprague-Dawley male rats were placed into a stereostaxic apparatus,1μl of ET-1(200 pmol),kainic acid(KA,5 pmol) or PBS was injected into the right dorsal hippocampus, respectively.Then all rats were then monitored for at least 2 h with an electroencephalography and a video.Nissl staining,glial fibrillary acidic protein(GFAP) staining at 48 h and Neo-Timm staining at 30 d after the injection for mossy fiber sprouting(MFS) scoring was performed,respectively.Result:After the intrahippocampal injection of PBS,the rates showed no seizures with 10-15 Hz, 150-200μV electroencephalographic activities.All rats in group ET and group KA demonstrated different kinds of seizures companied with electrographic seizure activities(slow or sharp-slow waves).The grade 3-5 seizure rate in KA group,however,was significant higher than that in ET-1 group(86.67%Vs 16.67%,P＜0.05).Some ET-1 and KA treated rats showed also seizures 2-3 weeks after the injection.Compared with PBS group,less Nissl stained cells, more GFAP staining cells,and higher MFS score at contralateral hippocampus of the injection in KA and ET-1 treated rats were evident(each P＜0.05,respectively).Conclusion:Intrahippocampal injection of ET-1 can induce epileptic seizure activities and hippocampal sclerosis in rats.That is over expression of ET-1 may partly induce to the development of hippocampal sclerosis,which may also be another important reason of temporal epilepsy.