The Expression Of Epo-R, JAK2, STAT-3, PI3kandAKT In The Human Brain With Refractory Epilepsy

Objctive:To explore the expression of EPO-R，JAK2，STAT-3，PI3KandAKT in thehuman brain with refractory epilepsy and the role of them in neural apoptosis.Background:It is well known that recurrent seizures induced neuronal apoptosis in the animalepileptic model,and clinical neuroimaging studies also support this view. thepathological damage of the central nervous system induced by neuron apoptosis willrepeat and superimpose constantly.so that it is difficult to control the epileptic seizuresand improve the cognitive impairment,which not only has a harmful effect on patientsthemselves,but also bring a heavy burden to the family and society.Based on the studyfor neuropretection,in order to provide theoretical fundamentals for clinical epilepsytreatments, studies have found that EPO can reduce nerve cells apoptosis,reduce thenumber of seizures,and improve the symptoms of epilepsy in recent years,EPO mayplay an role in neuroprorection by activating EPO-R/JAK2/STAT-3,and EPO-R/PI3K/AKT pathway,it has been demonstrated that the expression of EPO-R increasedin animal status epilepticus,but the protein expression of EPO-R、JAK2、STAT-3、PI3K and AKT in the human brain with intractable epilepsy has not been reported.Materials and methods:Collecting the informations of24experimental group patients with diagnosis ofrefractory epilepsy and after surgical treatment,who were in the epilepsy center of theBethune first hospital of Jilin University from March2010to May2011.6controlgroup cases was collecting temporal lobe or frontal lobe brain tissue which fromautopsy of unnatural death over the same period,collected the brain tissues to observethe expression of EPO-R、JAK2、STAT-3、PI3K and AKT in the brain tissue throughimmunohistochemicalstudy,then analysed the result with statistical method Results:1.①The expression of EPO-R、JAK2、STAT-3、PI3K and AKT are found in bothexperimental and control groups.The positive cell numbers of EPO-R、JAK2、STAT-3、PI3K and AKT expression were41.73±3.81、53.65±3.41、45.52±2.62、38.72±1.58、31.23±2.54in brain tissues in the experimental group. the numbers ofpositive cells were23.10±1.53、26.33±0.59、20.87±1.19、20.57±0.66、21.10±1.91incontrol group.there were significant differences between the experimental and controlgroup (P＜0.001).②The expression level of EPO-R、JAK2、STAT-3、PI3K and AKTin the brain tissue of patients with different seizure frequency. the numbers of positivecells were40.49±3.94、52.41±3.19、44.27±2.16、37.73±1.45、30.24±2.39in the groupof lower than10attacks per month, the numbers of positive cells were43.78±2.62、55.71±2.81、47.60±1.95、39.44±1.75、32.87±1.90in the group of10times and morethan10times per month. there were significant differences between the two groups(P＜0.05).③The expression level of EPO-R、JAK2、STAT-3、PI3K and AKT in thebrain tissue of patients with different duration. the numbers of positive cellswere40.44±3.70、52.31±3.24、44.70±2.37、37.73±1.25、30.00±2.03in the group oflower than10years, the numbers of positive cells were44.30±2.62、56.33±1.85、47.15±2.45、39.68±1.96、33.68±1.43in the group of10years and more than10years.there were significant differences between the two groups(P＜0.05).2.The structural changes of experimentalgroup brain were observed under theoptical microscope and electron microscope. The distribution of nerve cells wereuneven under the optical microscope,the nucles was vacuolated,the cytoplasm wasless and gliocyte was more.under the transmission electron microscope,the number ofneurons decreased,nuclear condensated,the heterochromatin was increased,thenucleolus were dissymmetry and the nuclear membrane wasbreakage,neurons becamepyknotic,cell body became smaller,astrocytecell membrane became edema,chromatinwas dissymmetry,some mitochondrial were swelling and transparent,and others werevacuolated,the mitochondrial crista disorder also can be observed.Conclusion:1.There are some neuronal apoptosis in the human brain with intractable epilepsy. 2.EPO-R、JAK2、STAT-3、PI3K and AKT are widely expressed in neurons andglial cells with refractory epilepsy,which was significantly increased, compared withcontrol group.the expression of EPO-R、JAK2、STAT-3、PI3K and AKT is related tothe frequency and the duration of epileptic seizures.3.The signal pathway of EPO-R/JAK2/STAT-3and EPO-R/PI3K/AKT may beinvolved in the pathophysiological process of endogenous EPO in neuroprotectionafter the seizureInnovation points:To our knowledge,EPO-R、JAK2、STAT-3、PI3K and AKT in the human brainwith intractable epilepsy was first studied and reported at home and abroad.