Functional And Mechanistic Study Of Dexamethasone In The Treatment Of Chronic Subdural Hematoma

Chronic subdural hematoma(CSDH)is a common disease in neurosurgery.At present,the first-line treatment of CSDH patients is still the removal of hematoma by cone or drilling.However,these surgical methods have a high recurrence rate of hematoma and the incidence of surgical related complications.Therefore,the development of targeted adjuvant therapy is an important research field for neurosurgeons.Combined with the latest literature review and the previous research of the research group,it is found that the complex pathophysiological pathways,such as the local angiogenesis disorder of the capsule of hematoma,the imbalance of local immune inflammatory response,and the abnormal coagulation function in the hematoma cavity,are involved in the occurrence,development and outcome of CSDH.Intervention with statins can promote the absorption of hematoma,reduce the rate of operation and postoperative recurrence.However,the effect of atorvastatin alone on CSDH is slow;the duration of treatment is long;and some patients still need surgery.Atorvastatin has a weak inhibitory effect on inflammatory response,it can not control the inflammatory response of CSDH rapidly.On this basis,we propose whether the inhibition of inflammatory effect of intensive intervention can improve the therapeutic effect of drugs.We propose the research direction of this subject: “Fuctional and mechanistic study of dexamethasone in the treatment of chronic subdural hematoma”.In this study,firstly,the human brain microvascular endothelial cells were injured by hematoma fluid of CSDH patients to establish the model of CSDH vascular endothelial injury in vitro;Dexamethasone intervention was given to test the function of endothelial cells;then RNA sequence was used to detect the changes of protein transcription level in different intervention groups.The clinical application of dexamethasone in CSDH patients was explored.A new model of spontaneous CSDH in rats was successfully established by using matrigel-bend.3 cell mixture.The results showed that dexamethasone assisted atorvastatin significantly enhanced the expression of tight junction protein in h CMEC/D3 cells and reduce the vascular permeability in vitro and in vivo.The transcriptional group of dexamethasone assisted atorvastatin treatment group changed significantly.Transcriptional factors KLF-2 may as the key target of dexamethasone assisted atorvastatin therapy which participated in the whole process of angiogenesis and inflammation regulation in CSDH.The clinical experiment found that dexamethasone assisted atorvastatin reduced the volume of hematoma,promote the recovery of nerve function and reduce the operation rate in CSDH patients.The detection of EPC,Treg and inflammatory factors in patients' peripheral blood suggested that dexamethasone assisted atorvastatin treatment has stronger anti-inflammatory and angiogenic effects.In addition,we established a new CSDH model in rats,which well simulated the spontaneous and progressive increase of hematoma in CSDH patients,and provided an important experimental animal platform for exploring the occurrence and development of CSDH diseases and drug treatment.In conclusion,this study preliminarily discussed the mechanism of dexamethasone in the treatment of CSDH;compared the difference between dexamethasone and statins;and preliminarily verified the optimized drug treatment scheme;and established a new model of spontaneous CSDH in rats,which provided the basic for further research on the CSDH.