Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice.

Abstract

This study examined whether chronic ad libitum intake of hydrogen-enriched electrochemically reduced water (H-ERW) influences the course of lipopolysaccharide (LPS)-induced neuroinflammation in C57Bl/6 mice. Animals received H-ERW for 7 days before a single intraperitoneal injection of LPS (0.33 mg/kg). Sickness behavior was evaluated 2 hours post-injection, and spontaneous locomotor activity was monitored for 72 hours. Real-time PCR analysis of hippocampal tissue revealed that H-ERW shifted baseline cytokine expression toward an anti-inflammatory profile, characterized by reduced TNF-α and elevated IL-10. Although the peak amplitude of neuroinflammation was increased, its duration was shortened and resolution was accelerated. Parallel experiments in BV-2 immortalized murine microglia reproduced these gene expression changes, implicating microglial modulation as a contributing mechanism. The findings indicate that cytokine expression regulation represents an important mechanism beyond free-radical scavenging through which molecular hydrogen exerts its neuroprotective actions.

Mechanism

H2 shifts hippocampal cytokine expression toward an anti-inflammatory profile by downregulating TNF-α and upregulating IL-10, while modulating microglial activation in BV-2 cells, thereby shortening the duration of LPS-induced neuroinflammation.