The Correlation Research Of DYRK1A Expression And Refractory Temporal Lobe Epilepsy

Objective: To establish a mice model of human temporal lobe epilepsy, lithium chloride-pilocarpine can be induced status epilepticus seizures in Kunming mice by intraperitoneal injection. The analysis of DYRKIA mRNA expression in mice’s brain tissue is used to investigate whether DYRKIA participate in the formation of hippocampal sclerosis of intractable temporal lobe epilepsy. By this, we can provide theoretical basis for the correlation between DYRKIA expression and hippocampal sclerosis in intractable temporal lobe epilepsy.Methods:clean healthy male Kunming mice were randomly divided into control group(6)and epileptic group (34). Epileptic group were established status epilepticus (SE) by injecting a small dose of lithium chloride-pilocarpine repeatedly and intraperitonealy. Control group can be injected by saline like this. Kunming mice were observed in the next24hours and30days. We randomly selected6mice into acute epileptic group,6mice into chronic epileptic group. On the basis of behavioral observation, electrophysiological, pathological HE staining method, we verified the reliability of the model and established mice model of human temporal lobe epilepsy. Reverse transcription PCR method was used to detect DYRKIA mRNA expression levels in the brain tissue of model mice.Results:There were34Kunming mice, which were be induced into status epilepticus seizures by intraperitoneal injection of lithium chloride-pilocarpine.22Kunming mice were established status epilepticus (SE) and reached Racine Standard IV-V level, excluding12mice, which didn’t meet Racine standards IV-V level.5of22mice died within24hours and3of22mice died within24-72hours. In24hours after SE,6mice were randomly selected into acute epilepsy group; The remaining8mice were observed within30days and6mice were selected into chronic epilepsy group;6mice in the control group were intraperitonealy injected by saline. They were not induced into any seizure and didn’t die in the next30days. In this study, a success rate of induced SE was64.71%(22/34), the mortality rate after SE was36.36%(8/22); spontaneous seizures occurred at the rate of47.06%(8/17). Pathology HE staining:in comparison with the control group, hippocampal neurons of epileptic group arranged irregularly and the gap between neurons increased, with cell swelling, degeneration, necrosis, disintegration, cell body pyknosis, smaller volume, cytoplasm condensed hyperchromatic, nucleus pycnosis, unclear nucleoli, splitting decomposition of dead cell nuclei and cytoplasm.EEG monitoring of epileptic mice models:in the acute phase, the outbreak of the long-range sharp activities, sharp spike activity and slow irregular composite activity was prominent in the background EEG activity; in the chronic phase, scattered frequency activities slower than the background slow activity and epileptic discharge appeared.In6control group, DYRK1A mRNA and β-actin ratio was0.4830±0.1243; in6acute epileptic group, DYRK1A mRNA and β-actin ratio was0.8883±0.0727; in6chronic epileptic group, DYRK1A mRNA and β-actin ratio was0.7112±0.1216; The ratio differences between three groups all were statistically significant (P <0.05). DYRK1A mRNA expression in three groups:acute cause epilepsy group> chronic epilepsy group>control group.CONCLUSIONS:Lithium chloride-pilocarpine can be used to induce status epilepticus (SE) in Kunming mice. In comparison with control group, DYRK1A expression in brain tissue of SE Kumming mice model increased.