Mechanism Of Traumatic Associated Macrophage Migration Inhibitory Factor Aggravating The Damage Of Blood Brain Barrier In Perioperative Stroke

Objective Perioperative stroke has received increasing attention due to its high morbidity and devastating consequences in surgical patients.Ischemic brain injury can be complicated by the effects of surgery,anesthesia,stress,pain,etc.However,the mechanism by which perioperative stroke exacerbates ischemic brain injury remains largely unknown.Macrophage migration inhibitory factor(MIF)is a multifunctional cytokine that is produced and stored in cytoplasmic cysts and can be rapidly released in response to a series of stimuli.It has been considered to be an inflammatory response and a pro-apoptotic nuclease.Important trigger factor.In this study,we will investigate the role of MIF in blood brain barrier(BBB)injury after perioperative stroke.Method and Results In my research,adult male C57/BL6(25-30g)mice were used to establish a tibial fracture internal fixation 24 hours before distal middle cerebral artery occlusion model(d MCAO)to establish a perioperative stroke model.The research is devided into three parts.The first part of experiment using 2,3,5-triphenyltetrazole chloride staining(TTC staining),Evans blue,immunofluorescence staining and dynamic contrast contrast magnetic resonance technology and behavioral tests demonstrated that perioperative ischemic stroke aggravates BBB damage,endothelial cell single strand DNA damage and apoptosis and neurological dysfunction.In the second part,venous blood of patients undergoing orthopedics,gastrointestinal surgery and other operations before and 1 day after surgery was detected by flow cytometry.Animal and cell experiments were performed to demonstrated that peripheral macrophage MIF expression caused by surgical trauma aggravates BBB damage and endothelia cells apoptosis during perioperative period.The third part uses small interfering ribonucleic acid(RNA)to knock down CD74 along with endocytosis experiment,immunofluorescence staining and polymerase chain reaction(PCR)demonstrated that macrophage-derived MIF enters endothelial cells through CD74 receptor-mediated endocytosis,aggravates endothelial cell DNA damage and causes endothelial cell apoptosis.Conclusion Peripheral surgical trauma induces the activation of macrophages and up-regulates MIF expression.After stroke,MIF secreted by macrophages enters endothelial cells through CD74 receptor-mediated endocytosis.It exerts its endonuclease activity to induce DNA damage to brain endothelial cells,cause apoptosis of endothelial cells,and aggravate BBB damage after perioperative stroke.