RIP1 / RIP3 / MLKL Pathway-mediated Programmed Necrosis In The Pathogenesis Of Cerebral Cavernous Malformations Complicated With Epilepsy

[Objective]: Detection of RIP1 and RIP3 of epilepsy lesions and epilepsy tissues diagnosed by Cerebral Cavernous Malformations(CCM)confirmed by clinical symptoms,imaging,neuroelectrophysiology,intraoperative navigation technology and postoperative pathological returns Expression,distribution and significance of MLKL and Rh OA.[Methods]: 1.Select from January 2012 to September 2019 with clinical symptoms,imaging,intraoperative navigation technology and surgical confirmation,intraoperative cortical electroencephalography(ECo G),and the occurrence of seizures confirms that the epileptic focus is related to the CCM was related and the postoperative pathological return was confirmed.According to the2017 Anti-Epileptic Coalition consensus standard classification,17 cases of cerebral cavernous hemangioma(CCM)lesions with epilepsy and epilepsy tissue were diagnosed,and cortical dysplasia with epilepsy Dysplasia(FCD)in 17 cases of epilepsy focus tissue,lateral ventricle space occupying,trauma,or cerebrovascular accident in patients with epilepsy which are unavoidable for surgical treatment of 10 cases of brain tissue;2.CCM group,FCD group lesions and epilepsy Tissues were routinely stained with HE;3.The expressions of RIP1,RIP3,MLKL,and Rho A proteins in the lesions and epilepsy tissues of the CCM group,FCD group,and control group were detected by a two-step immunohistochemical method,using Image-Pro Plus 6.0 The software selects the same brown-yellow color as the unified standard for judging the positive,and analyzes the cumulative optical density value(IOD)of the positive and the pixel area(AREA)of the tissue.Average optical density(average optical,AO value),AO = IOD / AREA,the larger the AO value,the higher the positive expression level;4.Western blotting detection of RIP1,RIP3,MLKL,Rho A in the CCM group,FCD group and control The content of protein was compared with the measurement result of the internal reference β-actin by the gel gray analysis software Quantity One 4.6.2,and the ratio was calculated to compare the differences between the groups.[Result]: 1.Immunohistochemical expression showed that the expression of RIP1,RIP3,and MLKL proteins in the CCM group and the control group was significantly different in the intensity of neurons(PRIP1 <0.0001,PRIP3 <0.0001,PMLKL <0.0001),the FCD group and the control group There was a significant difference in the expression intensity of neurons in the group,with statistical significance(P <0.05)(PRIP1 <0.0001,PRIP3 <0.0001,PMLKL <0.0001).There was no significant difference in the expression intensity of the neurons in the CCM group and the FCD group,which was not statistically significant.(P> 0.05)(PRIP1 =0.7397,PRIP3 = 0.9874,PMLKL = 0.5166).Rho A was expressed in the CCM group,but low in the FCD group and the control group.2.Western blotting test showed that RIP1,RIP3,and MLKL proteins were positively expressed in the brain tissue of the lesions in the CCM group and the FCD group,and the control group was negatively expressed.There was statistical significance(P <0.05)(PRIP1 <0.0001,PRIP3 <0.0001,PMLKL <0.0001),the expression intensity difference between the FCD group and the control group was significant and statistically significant(P<0.05)(PRIP1 <0.0001,PRIP3 <0.0001,PMLKL <0.0001);Rho A was expressed in the CCM group,but low in the FCD group and the control group.[Conclusion]: RIP1 / RIP3 / MLKL pathway-mediated programmed necrosis may be involved in the development of intracranial cavernous hemangioma and epilepsy.