Hydrogen alleviated neuronal injury and neuroinflammation induced by microglial activation via the Nrf2 pathway in sepsis-associated encephalopathy

Beibei Dong, Hongguang Chen, Ke-Liang Xie, Yonghao Yu, Yuan Shi

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DOI: 10.1016/j.neuroscience.2021.05.003 DOI is the universal ID for this study.

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Objective: Sepsis-associated encephalopathy (SAE) is characterized by diffuse cerebral and central nervous system (CNS) dysfunction. Microglia play a vital role in protecting the brain from neuronal damage, which is closely related to inflammatory responses. The Nrf2 signaling pathway has an impact on microglial and neuronal injury. Here, we mainly explored the molecular mechanism by which H2 regulates neuroinflammation in SAE and the role of Nrf2 in this process.

Methods: An in vivo model of SAE was generated by cecal ligation and puncture (CLP). Primary microglia and neurons were cultured to establish an in vitro model. Microglia, neurons and brain tissue were obtained to detect Nrf2 expression, inflammation, cell injury, apoptosis, and microglial polarization. Escape latency, the number of platform crossings and the time spent in the target quadrant were measured to assess cognitive function.

Results: H2 attenuated microglial polarization from the M1 to the M2 phenotype, cytokine release and TLR/NF-κb activation and protected neurons from LPS-activated microglia-induced injury via the Nrf2 pathway. SAE activated Nrf2 expression, and H2 further improved Nrf2 expression in SAE mice. H2 alleviated microglial polarization from the M1 to the M2 phenotype and cytokine release in the cerebral cortex and improved neuronal injury or cognitive dysfunction in SAE mice and wild-type mice but not in Nrf2-/- mice.

Conclusion: H2 exerts antineuroinflammatory effects associated with TLR4/NF-κB signaling activation and neuroprotective effects by inhibiting the excessive release of proinflammatory cytokines, neuronal loss and apoptosis in vitro and in vivo through the Nrf2 pathway.

Publish Year 2021
Country China
Rank Positive
Journal Neuroscience
Primary Topic Brain
Secondary TopicSepsis
Model Cell Culture
Tertiary TopicEncephalopathy
Vehicle Medium (Dissolved)
pH Neutral
Application Culture Media