DUSP19 mediates spinal cord injury-induced apoptosis and inflammation in mouse primary microglia cells via the NF-kB signaling pathway.

Objective: Spinal cord injury (SCI) is a common injury that seriously threatens human health. NF-κB may be involved in the secondary injury of SCI that is mediated by inflammation and aggravates damage. Our study was aimed to investigate the role of NF-κB signaling in DUSP19-mediated cleaved Caspase-3 expression and the release of inflammatory factors in vivo and in vitro.Materials and Methods: DUSP19 mRNA expression and the content of IL-6 and IL-8 in patients with traumatic SCI (TSCI) were measured by real-time PCR and ELISA, respectively. The levels of p-NF-κBp65, NF-κBp65 and cleaved Caspase-3 expression and the concentrations of IL-6 and IL-8 were measured by western blotting and ELISA, respectively.Results: Patients with TSCI showed lower DUSP19 expression and higher concentration of IL-6 and IL-8 compared with healthy controls. DUSP19 overexpression inhibited p-NF-κBp65 level, cleaved Caspase-3 expression, and production of IL-8 and IL-6 in the mice induced by TSCI. DUSP19 silencing increased p-NF-κBp65 level, cleaved Caspase-3 expression, and concentration of IL-6 and IL-8 in mouse primary microglia cells. DUSP19 overexpression had an inverse effect. Importantly, DUSP19 silencing and overexpression mediated p-NF-κBp65 level, cleaved Caspase-3 expression, and concentration of IL-6 and IL-8 in mouse primary microglia cells were reversed by NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) and NF-κB activator 12-myristate 13-acetate (PMA), respectively.Conclusion: These results suggested that DUSP19-mediated SCI-induced apoptosis and inflammation via NF-κB signaling and might therefore serve as a potential therapeutic target for SCI.

A simple disc degeneration model induced by percutaneous needle puncture in the rat tail.

STUDY DESIGN: : We evaluated the degenerative changes to rat tail vertebral discs induced by percutaneous needle puncture, and we compared 2 puncture styles for the depth of needle puncture and the rate of disc degeneration. OBJECTIVE: : To develop a simple animal model of disc degeneration. SUMMARY OF BACKGROUND DATA: : The study of biologically based treatments for degenerative disc disease depends largely on animal models. Annulus needle puncture in the lumbar spine inducing disc degeneration in rabbits has proven successful, but a similar method has not been evaluated in the tail discs of rats, even though it might produce a desirable model for disc repair studies. METHODS: : Two consecutive rat tail vertebral discs, proximal and distal to the eighth coccygeal vertebra, were randomized for injury and control. The disc selected for injury was punctured percutaneously using a 20-gauge needle with either full penetration or half penetration. The discs were harvested 1, 2, and 4 weeks later. Measurements included disc height on molybdenum target digital radiographs, biochemistry (water content, glycosaminoglycans, and hydroxyproline), and histology. RESULTS: : Needle punctures with full or half penetration caused significant disc space narrowing and progressive histologic changes of degeneration as early as 1 and 2 weeks after injury, respectively. Significant decrease in glycosaminoglycan content was observed at 4 weeks in the half-penetration puncture discs and at 2 and 4 weeks in discs punctured penetratively. Penetrative puncture resulted in a faster decrease in disc height, lower glycosaminoglycan content, and higher grades of histologic degeneration. The water and hydroxyproline content of the discs did not change appreciably. CONCLUSION: : Tail disc percutaneous needle puncture is a simple method for inducing disc degeneration and the rate of degeneration is positively related to the depth of needle puncture. This model still has some limitations that should be taken into consideration when results of disc regeneration research in this model are interpreted and extrapolated to human.