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<p>Traumatic brain injury (TBI) is a key health issue that causes oxidative stress, neuroinflammation, and severe neurological dysfunction. The overexpression of reactive oxygen species (ROS) and accumulation of inflammatory cytokines following TBI exacerbate neuronal damage and impair recovery. Herein, a novel tungsten-based polyoxometalate nanocluster (W-POM NC) is presented, which is designed to alleviate TBI-related damage by targeting oxidative stress and inflammation. W-POM NCs exhibit strong ROS-scavenging properties, reducing oxidative stress through a redox mechanism, and effectively suppressing the inflammatory response. Mechanistically, W-POM activates the Nuclear factor erythroid 2-related factor 2 (Nrf2)-Musculoaponeurotic fibrosarcoma (MAF) signaling pathway, inducing upregulation of heme oxygenase-1 (HO-1) and promoting neuronal survival. Compared to the positive control drug edaravone, W-POM administration demonstrated superior efficacy in reducing proinflammatory reactions and oxidative stress biomarkers in brain tissue. <i>In vivo</i> studies demonstrated that W-POM notably enhanced the survival rate of TBI-afflicted rats and improved their cognitive performance, as assessed by behavioral assays. This work also offers a feasible approach for enhancing the selectivity of polyoxometalates under physiological conditions and exploring their potential applications in brain science.</p> Graphical Abstract <p></p>

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Redox-driven polyoxometalate nanoclusters for mitigating neuroinflammation in traumatic brain injury through Nrf2-MAF signaling pathway activation

  • 期刊论文

  • 发表日期：

    2025年12月1日

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  • Guo-Hui Jiang,
  • Long Zhao,
  • Cheng-Hui Liu,
  • Jing-Ming Tong,
  • Jing Zhou,
  • Qi-Qi Xu,
  • Chuan Zhang,
  • Xiao-Xue Xu,
  • Xiao-Ping Tang,
  • Han-Feng Yang,
  • Yuan Yong

摘要

Traumatic brain injury (TBI) is a key health issue that causes oxidative stress, neuroinflammation, and severe neurological dysfunction. The overexpression of reactive oxygen species (ROS) and accumulation of inflammatory cytokines following TBI exacerbate neuronal damage and impair recovery. Herein, a novel tungsten-based polyoxometalate nanocluster (W-POM NC) is presented, which is designed to alleviate TBI-related damage by targeting oxidative stress and inflammation. W-POM NCs exhibit strong ROS-scavenging properties, reducing oxidative stress through a redox mechanism, and effectively suppressing the inflammatory response. Mechanistically, W-POM activates the Nuclear factor erythroid 2-related factor 2 (Nrf2)-Musculoaponeurotic fibrosarcoma (MAF) signaling pathway, inducing upregulation of heme oxygenase-1 (HO-1) and promoting neuronal survival. Compared to the positive control drug edaravone, W-POM administration demonstrated superior efficacy in reducing proinflammatory reactions and oxidative stress biomarkers in brain tissue. In vivo studies demonstrated that W-POM notably enhanced the survival rate of TBI-afflicted rats and improved their cognitive performance, as assessed by behavioral assays. This work also offers a feasible approach for enhancing the selectivity of polyoxometalates under physiological conditions and exploring their potential applications in brain science.

Graphical Abstract