Efficacy And Mechanism Of Release CXCL12 To The Schwann Cell Migration Of Damaged Facial Nerve And Repair Of Facial Nerve

Introduction and Objective Hemifacial spasm(HFS) is a common cranial nerve disease,which seriously affects the quality of life of the patients.Vascular compression of the root exit zone(REZ) of facial nerve resulted in facial nerve demyelination is the main pathogenesis of hemifacial spasm.The main reason for the ineffectiveness and recurrence of hemifacial spasm after microvascular decompression(MVD) is the lack of complete repair of facial nerve demyelination.At present,there is still lack of effective methods to promote facial nerve demyelination repair.Therefore,to promote complete repair of demyelination injury of facial nerve is the premise and structural basis for satisfying curative effect and ensuring normal nerve function after operation.Schwann cells play an important role in the structural repair and functional reconstruction after peripheral nerve injury.How can we make Schwann cells migrate to the injured area and secrete neurotrophic factors,which may be an effective way to promote repair of facial nerve.In this study,we imagine that the continuous injection of chemokine CXCL12 into the facial nerve demyelination area,to guide the migration of Schwann cells,promote the repair of myelin,and ultimately achieve complete repair of neural function.In addition,how to realize the continuous administration of the demyelination sites of the intracranial facial nerve roots and to form the effective concentration of CXCL12 is a realistic problem.In recent years,the progress of new material science,especially the emergence of nano hydrogel materials,provides a realistic condition for the solution of this problem.In this study we will from three aspects in this dissertation: first,sustained release effect of CXCL12 on the migration of Schwann cells and myelin repair of facial nerve function(in vitro and in vivo observation);two,release CXCL12 how to adjust the facial nerve injury zone microenvironment and promote nerve repair?(cytokine analysis);three.The molecular mechanism of chemokine CXCL12 promoting Schwann cell precursor migration and facial nerve repair(receptor pathway blocking test).We hope to provide a theoretical basis for the clinical efficacy of hemifacial spasm patients through the experimental results and molecular mechanisms.Method Part ?: We determined the effect of CXCL12/RADA16-? on Schwann cells in vitro.Part ?: We established a rabbit model of facial nerve injury by combining all kinds of detection methods to determine the appropriate parameters.Part ?: In vivo experiments,we used molecular biology and electrophysiological examination to determine the role of CXCL12 in promoting Schwann cell migration and facial nerve myelin repair.Part ?: We investigated the changes of local microenvironment in the damaged facial nerve by using the cytokine microarray technique under the action of sustained release CXCL12.Part ?: We used CXCR4 receptor pathway blocker AMD3100 to study the neural pathways of CXCL12 promoting Schwann cell migration and myelin repair.Results In the first section,by sustained release of CXCL12,CXCL12/RADA16-? persistent guide Schwann cell migration and have protective effects on Schwann cells.In the second section,through behavioral,electrophysiological and histological examination,we concluded that the animal model of 70 g compression injury in the facial nerve cistern of rabbit was consistent with the facial nerve demyelination model,which could provide a suitable animal model for subsequent experiments.In the third section,the repair of myelin sheath was observed by light and electron microscopy and the evaluation of functional recovery of facial nerve showed that Schwann cells in the demyelination area were clustered under the action of slow-release CXCL12,and these Schwann cells were involved in the repair of facial nerve myelin sheath.In the fourth section,through cytokine microarray,we found that Brain-derived neruratrophic factor(BDNF),Neural growth factor(NGF),were significantly increased in the local microenvironment of the damaged facial nerve under the action of sustained release CXCL12.In the fifth section,the effect of CXCL12 on the migration and myelin repair of Schwann cells was attenuated after the addition of CXCR4 receptor pathway inhibitor AMD3100.There was no significant difference between the study group and the control group.The results suggest that CXCL12 plays a role in the CXCR4-CXCR7 receptor pathway in vivo.Conclusion This study demonstrates that CXCL12/RADA16-? can be sustained release of CXCL12,so as to guide the migration of Schwann cells and can obviously promote the repair of myelin sheath after facial nerve demyelination in rabbit.The mechanism is related to the increase of cytokines in the injured zone of facial nerve;the release of CXCL12 in vivo has the function of repairing myelin of the facial nerve through the CXCR4-CXCR7 receptor pathway.