title: Selective inhibition of STAT1 reduces spinal cord injury in mice.
abstract: The signal transducer and activator of transcription 1 (STAT1) is associated with neuronal cell death after cerebral ischemia. However, the role of STAT1 in the spinal cord injury (SCI) remains unclear. Here, we examined whether STAT1 blockade reduces neural tissue damage and locomotor impairment after SCI in mice. The small interfering RNA against STAT1 (STAT1 siRNA) or control non-targeting siRNA was injected intraperitoneally into SCI mice. Histological damage and locomotor function were evaluated. Inflammatory markers and apoptosis were determined. STAT1 siRNA treatment significantly decreased the histological damage following SCI. STAT1 siRNA-treated mice showed significantly improved locomotor function compared with the controls. Furthermore, TNF-α, IL-1β, and IL-6 levels at the injured site from the STAT1 siRNA-treated group were significantly reduced and IL-10 increased, in comparison with controls. The NF-κB activation and apoptosis in SCI were also inhibited. These results reveal that selective STAT1 inhibition reduced neural tissue damage and locomotor impairment by regulating inflammatory response and possibly apoptosis. STAT1 represents a novel therapeutic target after SCI.
authors: Department of Hand Surgery, First Hospital of Liaoning Medical University, Jinzhou 121000, Liaoning, China.
authors: Yuexin
authors: Y
authors: Wu
authors: Department of Hand Surgery, First Hospital of Liaoning Medical University, Jinzhou 121000, Liaoning, China. Electronic address: lnyanglimin@163.com.
authors: Limin
authors: L
authors: Yang
authors: Department of Spine, First Hospital of Liaoning Medical University, Jinzhou 121000, Liaoning, China.
authors: Xifan
authors: X
authors: Mei
authors: Department of Spine, First Hospital of Liaoning Medical University, Jinzhou 121000, Liaoning, China.
authors: Yang
authors: Y
authors: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism; D005260:Female; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D051996:Transcription Factor RelA
keywords: Inflammation; STAT1; Small interfering RNA; Spinal cord injury