Excessive inflammation post-traumatic spinal cord injury (SCI) induces microglial activation,which leads to prolonged neurological dysfunction.However,the mechanism underlying microglial activation-induced neuroinflammation remains poorly understood.Ruxolitinib(RUX),a selective inhibitor of JAK1/2,was recently reported to inhibit inflammatory storms caused by SARS-CoV-2 in the lung.However,its role in disrupting inflammation post-SCI has not been confirmed.In this study,microglia were treated with RUX for 24 hours and then activated with interferon-y for 6 hours.The results showed that interferon-γ-induced phosphorylation of JAK and STAT in microglia was inhibited,and the mRNA expression levels of pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,interleukin-6,and cell proliferation marker Ki67 were reduced.In further in vivo experiments,a mouse model of spinal cord injury was treated intragastrically with RUX for 3 successive days,and the findings suggest that RUX can inhibit microglial proliferation by inhibiting the interferon-γ/JAK/STAT pathway.Moreover,microglia treated with RUX centripetally migrated toward injured foci,remaining limited and compacted within the glial scar,which resulted in axon preservation and less demyelination.Moreover,the protein expression levels of tumor necrosis factor-α,interleukin-1β,and interleukin-6 were reduced.The neuromotor function of SCI mice also recovered.These findings suggest that RUX can inhibit neuroinflammation through inhibiting the interferon-γ/JAK/STAT pathway,thereby reducing secondary injury after SCI and producing neuroprotective effects.

Zhan-Yang Qian;Ren-Yi Kong;Sheng Zhang;Bin-Yu Wang;Jie Chang;Jiang Cao;Chao-Qin Wu;Zi-Yan Huang;Ao Duan;Hai-Jun Li;Lei Yang;Xiao-Jian Cao

Spine Center,Zhongda Hospital of Southeast University,Nanjing,Jiangsu Province,China;Medical School,Southeast University,Nanjing,Jiangsu Province,China;Department of Orthopedics,First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu Province,China;Department of Orthopedics,Hospital Affiliated 5 to Nantong University (Taizhou People's Hospital),Taizhou,Jiangsu Province,China;Taizhou Clinical Medical School of Nanjing Medical University,Taizhou People's Hospital,Taizhou,Jiangsu Province,China

中国神经再生研究（英文版）

[1]Zhan-Yang Qian;Ren-Yi Kong;Sheng Zhang;Bin-Yu Wang;Jie Chang;Jiang Cao;Chao-Qin Wu;Zi-Yan Huang;Ao Duan;Hai-Jun Li;Lei Yang;Xiao-Jian Cao-.Ruxolitinib attenuates secondary injury after traumatic spinal cord injury)[J].中国神经再生研究（英文版）,2022(09):2029-2035

RUX,centripetally,neuromotor

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