The Expression Of ERK1/2、Caspase-3in The Human Brain With Refractory Epilepsy

To ensure the expression of ERK1/2,Caspase-3in the human brain tissue withrefractory epilepsy and research the relationship between ERK signaling pathway andneuronal apoptosis、glial cell proliferation in these patients’s brain tissue.Background:In recent years, people pay more and more attention to the role of signalingpathway in seizure, ERK signaling pathway is one of the studied pathways which takeadvantage of animal models with epilepsy. ERK signaling pathway is an importantpathway which transfers information in eukaryotic cells. The pathway can respond toa variety of stimuli, such as growth factors, neurotransmitters, and other inflammatorycytokine, mainly activated by the Ras-Raf-1-MEK-ERK cascade signalingpathways.The activated ERK are phosphorylated and key information is passed to thecore, which makes a series of transcription factors phosphorylated and then start theprocess of signal transduction, which are involved in cell growth, proliferation,differentiation and apoptosis. However, so far studies of the expressions of theepileptogenic zone in intractable epilepsy at home and abroad are limited.Materials and methods:Collecting the information of the experimental group of24patients with diagnosisof refractory epilepsy and simultaneous surgical treatment in the epilepsy center of theBethune first hospital of Jilin University from September2010to May2012, as wellas control group cases of temporal lobe or frontal lobe brain tissue which are fromautopsies of unnatural death, this study will observe the expressions of ERK1/2，Caspase-3in the two brain tissues through immunohistochemical method, and analyzethe results with statistical method.Results:1.①Under the400times Light microscopy, the expressions of ERK1/2, Caspase-3were found in both experimental and control groups. The positive cell numbers ofERK1/2and Caspase-3of the experimental group were13.08±5.90、28.04±6.87inbrain tissues, while the numbers of positive cells were6.00±0.00、16.00±1.41in the control group. There are significant differences between the experimental and controlgroup, which has statistical significance.②The expression level of ERK1/2,Caspase-3in the brain tissue of patients with different seizure frequency. The numbersof positive cells were13.31±5.88、28.38±6.15in the group, which is less than10attacks per month, while the numbers of positive cells were12.82±6.19、27.64±7.92in the group which is of10times and more than10times per month. There were notobvious differences between the two groups (P＞0.05). In the group of lower than10years, the numbers of positive cells of the patients were14.38±5.50、27.75±7.00，,while in the group of10years and more than10years. the numbers of positive cellswere10.50±6.16、28.63±7.03. There were not obvious differences between the twogroups(P＞0.05).2.The brain structural changes of the case group: under the light microscope, thequantity of the nerve cells were decreased, the distribution of them were uneven,meanwhile degeneration and necrosis often occurred in the nerve cells, the nucles wasvacuolated, the cytoplasm was reduced and gliocyte shows hyperpiasia. under theelectron microscope,the number of neurons reduced, degeneration and necrosishappened in these cells, the nuclear membrane was breaked nuclear condensated,and the nucleolus were asymmetric,the heterochromatin was increased, and cellvolume became smaller, astrocyte cell became edema, chromatin was asymmetric,some mitochondrial were transparent and swelling, and some of them werevacuolated,the mitochondrial crista disorder also can happened.Conclusion:1.There are some neuronal apoptosis and gliocyte proliferation in the human brainwith intractable epilepsy.2.This study observed:ERK are widely expressed in neurons and with refractoryepilepsy, Caspase-3are widely expressed both in neurons and neurogliocytes, whichwas significantly more than control group, P＜0.05, which has statistical significance.But the expression of ERK and Caspase-3is not related to the frequency and theduration of epileptic seizures.3.The signal pathway of ERK and Caspase-3may be involved in thepathophysiological process of nerve cell apoptosis and gliocyte proliferation after theseizure Innovation points:Currently for the ERK1/2, Caspase-3expression in brain tissues, many studiestake use of animal models with epilepsy, but studies use patients brain tissues withrefractory epilepsy were less in the domestic and overseas. this study is more in linewith the pathophysiology of epilepsy, studying the ERK pathway inhibitors canprovide a theoretical basis to control epileptic seizures.