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

doi:10.5847/wjem.j.1920-8642.2025.057

Abstract

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 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.

Key words: Mannitol, Vancomycin, Methicillin-resistant Staphylococcus aureus, Endothelial glycocalyx, Filamentous actin

Yin Wen, Zhiwei Su, Huishan Zhu, Mengting Liu, Zhuo Li, Shiying Zhang, Shuangming Cai, Jiaqi Tang, Hongguang Ding, Hongke Zeng. 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[J]. World Journal of Emergency Medicine, 2025, 16(3): 239-247.

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