Mannitol-facilitated entry of vancomycin into the central nervous system inhibits neuroinflammation in a rat model of MRSA intracranial infection by modulating brain endothelial cells
Year: 2025
Type: article
Abstract: 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 fl uorescein (NaF) in the brain tissues of rats and fl uorescein 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 eff ects of mannitol and vancomycin in MRSA-infected rats.Syndecan-1 and fi lamentous 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 infl ammation, improved neurological function, and increased 7-day survival rate compared to rats treated with vancomycin and mannitol at 10hour intervals.Further experiments revealed that mannitol decreased the expression of syndecan-1 in brain tissues, which was confi rmed by in vitro experiments showing that mannitol signifi cantly decreased syndecan-1 via F-actin depolymerization.CONCLUSION: Mannitol may enhance the therapeutic effi cacy of vancomycin against intracranial MRSA infection by decreasing the endothelial glycocalyx of the BBB via F-actin depolymerization.
Authors: Yin Wen, Zhiwei Su, Huishan Zhu, Mengting Liu, Zhuo Li, Shiying Zhang, Shuangming Cai, Jiaqi Tang, Hongguang Ding, Hongke Zeng
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4410474485