Objective To optimize the simulation of the pathological characteristics and seizure behavior of medial temporal lobe epilepsy(MTLE),we aimed to establish a chronic epilepsy model of MTLE by unilateral,single hippocampal injection of kainic acid(KA)via stereotactic surgery,and to validate this epilepsy model in terms of behavior,electrophysiology,and pathology.Methods A total of 22 healthy C57BL/6 wild-type male mice were divided randomly into a control group(n=6)and an experimental group,which received KA injections(n=16).Both groups underwent microinjection of equal doses of saline or KA in the hippocampal CA3 area via stereotactic surgery.One week later,all mice were implanted with electrodes in the hippocampal CA3 area to facilitate electroencephalogram(EEG)recording.Seizure frequency and duration were analyzed statistically.The chronic epilepsy model was assessed in terms of behavior,electrophysiology,and pathology.Results No mice in the control group experienced seizures,while all surviving mice in the experimental group developed seizures.Adult model mice exhibited chronic spontaneous seizure behaviors,such as staring,chewing,head and facial muscle twitching,and limb spasms.Two mice died as a result of the surgery,four mice died during the acute seizure phase,and ten model mice were successfully established.EEG recordings showed epileptiform changes consistent with MTLE.Immunofluorescence staining revealed neuronal loss in the CA3 area and astrocytic changes,consistent with characteristic pathological changes of hippocampal sclerosis.Conclusions The model constructed by single unilateral intrahippocampal KA injection demonstrated several advantages such as being time-efficient,easy to operate,and reproducible.This model exhibited EEG,behavioral,and neuropathological changes similar to human MTLE,making it valuable for studying effective treatments for temporal lobe epilepsy and serving as an ideal animal model for predicting outcomes of epilepsy surgery.