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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Acrylamides, Alcohol Oxidoreductases, Animals, Cytokines, Disease Models, Animal, Enzyme Inhibitors, Gene Expression Regulation, In Situ Nick-End Labeling, Laminectomy, Male, Mice, Movement Disorders, NF-kappa B, Nerve Growth Factors, Nerve Tissue Proteins, Neutrophil Infiltration, Nicotinamide Phosphoribosyltransferase, Peroxidase, Phosphorylation, Piperidines, Silver Staining, Spinal Cord, Spinal Cord Injuries, Time Factors.
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Does the NAMPT inhibitor FK866 revert the damage in spinal cord injury? Context: Emerging data implicate nicotinamide phosphoribosyl transferase (NAMPT) in the pathogenesis of cancer and inflammation. NAMPT inhibitors have proven beneficial in inflammatory animal models of arthritis and endotoxic shock as well as in autoimmune encephalitis. Given the role of inflammatory responses in spinal cord injury (SCI), the effect of NAMPT inhibitors was examined in this setting. We investigated the effects of the NAMPT inhibitor FK866 in an experimental compression model of SCI. Twenty-four hr following induction of SCI, a significant functional deficit accompanied widespread edema, demyelination, neuron loss and a substantial increase in TNF-α, IL-1β, PAR, NAMPT, Bax, MPO activity, NF-κB activation, astrogliosis and microglial activation was observed. Meanwhile, the expression of neurotrophins BDNF, GDNF, NT3 and anti-apoptotic Bcl-2 decreased significantly. Treatment with FK866 (10 mg/kg), the best known and characterized NAMPT inhibitor, at 1 h and 6 h after SCI rescued motor function, preserved perilesional gray and white matter, restored anti-apoptotic and neurotrophic factors, prevented the activation of neutrophils, microglia and astrocytes and inhibited the elevation of NAMPT, PAR, TNF-α, IL-1β, Bax expression and NF-κB activity.We show for the first time that FK866, a specific inhibitor of NAMPT, administered after SCI, is capable of reducing the secondary inflammatory injury and partly reduce permanent damage. We also show that NAMPT protein levels are increased upon SCI in the perilesional area which can be corrected by administration of FK866.
assistant
Our findings suggest that the inflammatory component associated to SCI is the primary target of these inhibitors. Final Decision: yes