Study On Establishment Of Mouse Model Of Medial Temporal Lobe Epilepsy With Kainic Acid

Objective:Epilepsy,as a common,chronic,recurrent,non-infectious brain disease caused by multiple causes,affects approximately 65 million patients of all ages worldwide.The prevalence of epilepsy in my country ranges from 0.4% to 1.0%.Most of these patients can control their symptoms with reasonable antiepileptic drugs(AEDs),but about 10 million patients still develop drug-resistant epilepsy.Medial temporal lobe epilepsy(MTLE)is the most common focal and drug-resistant epilepsy.Epilepsy surgery is an important treatment method.In addition to the more classic epilepsy focus resection surgery,there are relatively new ablation surgery and neuromodulation.Both techniques can be used to treat intractable epilepsy.An ideal animal model of epilepsy can be used to study the pathogenesis of epilepsy and evaluate new antiepileptic drugs.Since the pathological characteristics and seizure behavior of MTLE can be simulated to the greatest extent in the epilepsy model of kanic acid(KA),this experiment established a chronic epilepsy model of MTLE by injecting KA into the hippocampus unilaterally.We verified the validity of the epilepsy model from behavior,electrophysiology and pathology.Methods:In this experiment,a model of chronic epilepsy of MTLE was constructed by unilateral and single hippocampal injection of KA by stereotactic surgery.Twelve healthy C57BL/6 male wild-type rats were used for experiment and randomly divided into a control group(n=4)and an experimental group i.e.KA injection group(n=8).The control group and the experimental group were micro-injected with the same dose of normal saline and KA in the CA3 region of the hippocampus through stereotaxic surgery.One week later,all mice were implanted with electrodes in the CA3 region of the hippocampus through stereotaxic surgery again to facilitate recording of EEG.One week after electrode implantation,the collection of EEG in mice was started,and the number and duration of seizures in epileptic mice were statistically analyzed.Through the observation and recording of mice,the chronic epilepsy model was verified from the aspects of behavior,electrophysiology and pathology.Results:In this experiment,12 C57BL/6 wild-type male mice were tested.The control group(n=4)had no epileptic seizures,while the surviving mice in the experimental group(n=8)all had epileptic seizures.Behaviors such as staring,chewing,head and face muscle twitching,limb spasm and other chronic epileptic spontaneous seizures occurred,1mouse died due to surgery,3 mice died in the acute attack period,and 4 mouse models were successfully established.The EEG showed epileptiform EEG changes in the medial temporal lobe;in terms of histopathology,immunofluorescence staining revealed that neurons in the CA3 area were lost and astrocytes(AC)proliferated massively,which was consistent with the characteristics of hippocampal sclerosis pathological changes.Conclusion:1.In this experiment,a chronic epilepsy model of MTLE was successfully constructed by unilateral and single intracranial injection of KA,and the behavioral,electrophysiological and pathological aspects were verified.2.The KA model has the following advantages: short time consumption,easy operation,drug cost saving,easy molding and permanent,and dose-dependent on KA.3.The epilepsy model constructed in the experiment has EEG,behavioral and neuropathological changes similar to human MTLE,which is helpful for the study of effective drugs for the treatment of temporal lobe epilepsy,and is an ideal animal model for the prognosis of epilepsy surgery.