Your browser doesn't support javascript.
Ruxolitinib attenuates secondary injury after traumatic spinal cord injury.
Qian, Zhan-Yang; Kong, Ren-Yi; Zhang, Sheng; Wang, Bin-Yu; Chang, Jie; Cao, Jiang; Wu, Chao-Qin; Huang, Zi-Yan; Duan, Ao; Li, Hai-Jun; Yang, Lei; Cao, Xiao-Jian.
  • Qian ZY; Spine Center, Zhongda Hospital of Southeast University; Medical School, Southeast University, Nanjing, Jiangsu Province, China.
  • Kong RY; Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Zhang S; Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Wang BY; Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Chang J; Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Cao J; Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Wu CQ; Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Huang ZY; Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Duan A; Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Li HJ; Department of Orthopedics, Hospital Affiliated 5 to Nantong University (Taizhou People's Hospital); Taizhou Clinical Medical School of Nanjing Medical University, Taizhou People's Hospital, Taizhou, Jiangsu Province, China.
  • Yang L; Department of Orthopedics, Hospital Affiliated 5 to Nantong University (Taizhou People's Hospital); Taizhou Clinical Medical School of Nanjing Medical University, Taizhou People's Hospital, Taizhou, Jiangsu Province, China.
  • Cao XJ; Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Neural Regen Res ; 17(9): 2029-2035, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1687156
ABSTRACT
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-γ 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-1ß, 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-1ß, 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.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: Neural Regen Res Year: 2022 Document Type: Article Affiliation country: 1673-5374.335165

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: Neural Regen Res Year: 2022 Document Type: Article Affiliation country: 1673-5374.335165