Experimental Study Of Establishing The Mouse Models Of Acute Epilepsy Induced By Kainic Acid

Epilepsy is a common neurological disorder.Statistics showed that the morbidity rate of epilepsy in China was about 7.0‰.So there are about 9 million patients affected by epilepsy in China.Epilepsy carries a substantial burden of illness,which is reflected in poor quality of life(QOL),psychosocial function and higher care resource use.The influence of epilepsy on patients'lives may be quite destructive and impaired QOL.Seizure,cognitive, emotional and behavioral status,social function, self-esteem, stigma seem to be crucial to QOL. It has been gradually recognized that seizure control is only one aspect of comprehensive management on epilepsy. It is widely pointed out that the purpose of treating epilepsy is not necessarily seizure eradiation rather the aim should be at obtaining maximal improvement of patients'quality of life.Temporal lobe epilepsy is the most common epilepsy syndrome in adults, accouting for more than 30%of partial epilepsy.About half of temporal lobe epilepsy is medically intractable.Temporal lobe epilepsy is a heterogeneous disorder with complex genetics in which putative susceptibility genes and environmental factors are believed to contribute to the etiologic and phenotype of the diseases. According to the focus of seizure origin,temporal lobe epilepsy is subclassificated as mesial temporal lobe epilepsy and lateral lobe epilepsy. Mesial temporal lobe epilepsy is regarded as the most common medically intractable epilepsy and early surgery may not only reduce seizure,but also improve cognitive and prognosis outcome.The kanic acid(KA)is a structural analogue of the aminoglutaminic acid,excitatory amino acid in the brain.KA model fulfils the perfect criteria of animal model of temporal epolepsy: 1.The hippocampus, amygdala and other limbic structures play a central role in its symptomatology; 2.The pattern of pathologic change is clearly reminiscent of Ammon's horn sclerosis in temporal epoleptic patients, including the neuronal cell loss, glia hyperplasia and mossy fiber sprouting. 3.There are spontaneous recurrent serzures in chronic phase. 4.Available anticonvulsants are weakly against the seizures generated by KA. So KA model can stimulate temporal epilepsy in human vividly. It is a good tool that can be used to research development and mechanism of epilepsy. KA model is used generally for the study in the epilepsy. Many scholars induced successfully epileptic animanl model by intraperitoneal injection of KA to investigate its pathogeniesin and therapeutics.In this investigation, the objective is to establish the kainate-induced temporal lobe epilepsy(TLE) model, study the morphology and electrophysiology's changement of hippocampal formation in the model mice, discuss the mechanism of pathologic changes and epileptogenesis in this model.Part One Establishing the mouse models of acute epilepsy induced by kainic acidObjective To establish the mouse models with acute epilepsy induced by kainic acid, and explore the characteristics. Methods 99 healthy male Kunming mice were selected and divided randomly into the saline group (n=33) and seizure-induced group (n=66). The seizure-induced group were treated with 10mg/kg kainic acid by intraperitoneal injection, and those in the saline group were treated with 35μl/g saline by intraperitoneal injection. After injection, the following 5 hours if there was seizure or not was observed continuously and was graded. When the seizure lasted for 1 hour, the mice were offered 4mg/kg diazepam by intraperitoneal injection. 3 in the control group and 9 in the seizure-induced group were monitored by electro encephalogram(EEG). The mice brains were sectioned and the pathologic change in the hippocampal area was checked by hemotoxylin-eosin (HE) staining. Results Totally 99 mice entered the final analysis.①On the praxiology, mice in model group showed wet dog shakes, the clonus of face, head and limbs, and generalized tonic-clonic convusions after injection of kainic acid.Epileptic seizure was not observed on mice in saline control group.②On the EEG, the mice of the status epilepticus could see the explosive slow wave of high amplitude of wave, spike wave or spike slow wave.③On the pathology, intraperitoneal injection could lead to neuronal degeneration in the bilateral hippocampus, mainly in the CA1 and hilar area. Conclusion The kainic acid induced mouse models with acute epilepsy is the same to the corresponding mice models with the characters of easy to make, short latency of seizure and high incidence mice etc. The developed acute epilepsy models have mimic features of human temparal lobe epilepsy, and the brain electric wave and neural pathology have changed.Part Two The comparison of epilepsy model reproduced by penicillin and kainic acidOvjective To establish the mouse models with acute epilepsy induced by kainic acid and penicillin, and explore the characteristics and condition of application. Methods 90 healthy male Kunming mice were selected and divided randomly into the saline group (n=10) and penicillin-induced group (n=40) and kainic acid-induced group (n=40). The kainic acid-induced group were treated with 10 mg/kg kainic acid by intraperitoneal injection, the penicillin-induced group were treated with 7×106 U/kg penicillin by intraperitoneal injection, and those in the saline group were treated with 35μL/g saline by intraperitoneal injection. After injection, the following 5 hours if there was seizure or not was observed continuously and was graded and was monitored by electro encephalogram(EEG). Results Totally 80 mice entered the final analysis. It was noted that the latency of the appearance of the status epilepticus by kainic acid was shorter than that by penicillin (P<0.05). The mortality rate was lower as well (P<0.05). Conclusion Acute epilepsy model reproduced by kainic acid might be superior to penicillin.