The Establishment Of Kainate-induced Temporal Lobe Epilepsy Model In Rat

Objective: To establish the kainite-induced model of temporal epilepsy in rat, observe the changes of symptome, EEG and pathology in the course of the model development, and the effect of valproate, discuss the mechanism of pathologic changes and epileptogenesis in this model.Methods: To make a epileptic focus, kainic acid (0.8 u g/0.2 u 1) was injected in the posterior ventral hippocampus via stereotactic technique. The symptome of the animals was recorded by a video camera. EEG signals was recorded by an EEG polygraph. The rats were killed at different phases. The pathologic examination of the samples were performed, including HE staining, Nissl staining, Timm's staining, TUNEL staining to observe the changes of neuron count, glia hyperplasia, mossy fiber sprouting and cell apoptosis in different phases and after VPA therapy.Results: The symptome of the rats could be divided clearly into three phases: the acute phase, the rats began local epilepsy immediatly after KA injection; silent phase, it was a period with no symptome after acute phase; chronic phase, the spontaneous recurrent seizures was the character of this phase, and existed persistently. The typical ictal and inter-ictal epileptiform activity was record in acute and chronic phase by EEG. By cell count, the neuronal cell loss was mainly occurred in acute phase and was worst in CAS and CA4. The cell loss in CA1 and CA2 was not serious, and the dentate gyrus was resistant. The apoptosis in hippocampus structure was detected by TUNEL staining. By Timm's staining, it was found that mossy fiber began sprouting in silent phase and increased continuously. Using adequate dose of VPA in early stage could prevent the progress of the disease. But after spontenaous seizures occurred, VPA could not control the seizure and the progress.Conclusions: KA model fulfils the perfect criteria of animal model of temporal epilepsy: 1. The hippocampus, amygdala and other limbic structures play a central role hi its symptomatology; 2. The pattern of pathologic change is clearly reminiscent of Ammon's horn sclerosis in temporal epileptic patients, including the neuronal cell loss, glia hyperplasia and mossy fiber sprouting. 3.There are spontaneous recurrent seizures in chronic phase. 4. Available anticonvulsants are weakly against the seizures generated by KA . So KA model can stimulate temporal epilepsy hi human vividly. It is a good tool that can be used to research development and mechanism of epilepsy.