摘要BACKGROUND:The present study aims to investigate whether mannitol facilitates central nervous system(CNS)entry of vancomycin and alleviates methicillin-resistant Staphylococcus aureus(MRSA)intracranial infection.METHODS:Blood-brain barrier(BBB)permeability was assessed by measuring the concentration of sodium fluorescein(NaF)in the brain tissues of rats and fluorescein isothiocyanate-dextran(FITC-dextran)in a single-cell layer model.Neutrophil infiltration in the brain tissue,inflammatory cytokine levels in the serum,neurological function,and 7-day survival rates were used to evaluate therapeutic effects of mannitol and vancomycin in MRSA-infected rats.Syndecan-1 and filamentous actin(F-actin)levels were measured,and the relationship between F-actin and the endothelial glycocalyx layer(EGL)was explored via the depolymerization agent cytochalasin D and the polymerization agent jasplakinolide.RESULTS:Following mannitol administration,the NaF and vancomycin concentrations in the brain tissue increased rapidly within 5 min and remained stable for 30 min,indicating that mannitol increased BBB permeability for 30 min.In vitro,mannitol treatment led to significantly greater FITC-dextran permeation through a single-cell layer compared to controls.In the MRSA intracranial infection model,rats treated with mannitol and vancomycin simultaneously presented less inflammation,improved neurological function,and increased 7-day survival rate compared to rats treated with vancomycin and mannitol at 10-hour intervals.Further experiments revealed that mannitol decreased the expression of syndecan-1 in brain tissues,which was confirmed by in vitro experiments showing that mannitol significantly decreased syndecan-1 via F-actin depolymerization.CONCLUSION:Mannitol may enhance the therapeutic efficacy of vancomycin against intracranial MRSA infection by decreasing the endothelial glycocalyx of the BBB via F-actin depolymerization.