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Updated: May 17, 2025
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Hydrogen Sulfide Modulates Microglial Polarization and Remodels the Injury Microenvironment to Promote Functional
Yu Wang1, Xinyi Jia1, Yuqi Zhang2
1Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Institute of Neuroscience, Soochow University, Departments of Rehabilitation Medicine and Neurology, The Fourth Affiliated Hospital of Soochow University, Suzhou, China.
Aims:
Spinal cord injury (SCI) disrupts tissue homeostasis, leading to persistent neuroinflammation and scar formation that severely impedes functional recovery. Current therapeutic approaches are insufficient to address these challenges. In this study, we investigated whether exogenous hydrogen sulfide (H2S) can modulate neuroinflammatory responses and remodel the injury microenvironment to promote tissue repair and restore motor function following SCI.
Methods:
T10 crush SCI was induced in mice, followed by daily intraperitoneal administration of the H2S donor anethole trithione (ADT). Immunofluorescence staining, tissue clearing, western blotting, and behavioral assessments were performed to evaluate scar formation, vascular regeneration, neuronal survival, and motor function.
Results:
ADT-based H2S therapy significantly promoted wound healing, inhibited scar formation, enhanced vascular regeneration, and protected residual neurons and axons from secondary injury. Mechanistically, H2S suppressed microglial proliferation and activation, promoting their polarization toward an anti-inflammatory phenotype and alleviating neuroinflammation. Consequently, motor function recovery was markedly improved.
Conclusion:
H2S modulates microglial activation and mitigates neuroinflammation, establishing a permissive microenvironment for SCI repair and significantly enhancing motor function recovery. Given ADT's established clinical safety and its effective gasotransmitter properties, our findings underscore its immediate translational potential for treating SCI.
