Objective: The aim of this study was to investigate the mechanisms of TUSC7/miR-449a/PPAR-gamma axis on the inflammation induced by microglia activation. Methods: A compressive spinal cord injury (SCI) model was established. The expressions of TUSC7, miR-449a PPAR-gamma, TNF-alpha and IL-1 beta in spinal cord tissues of SCI rats and HAPI cells were determined. The interaction of TUSC7 and miR-449a was tested by RIP and RNA pull-down assays. The regulatory relationship between miR-449a and PPAR-gamma was tested by dual luciferase reporter gene assay. Results: In the spinal cord tissue of SCI rats and HAPI cells induced by LPS, TUSC7 expression was reduced and miR-449a expression was increased. Overexpression of TUSC7 inhibited microglial activation and the expression of inflammatory factors (TNF-alpha and IL-1 beta). Moreover, we have found a targeting regulatory relation between TUSC7 and miR-449a, and a negative regulatory relationship between miR-449a and PPAR-gamma. In the study of molecular mechanism, we found that TUSC7 could regulate PPAR-gamma through miR-449a, and overexpression of TUSC7 inhibited microglial activation and the expression of inflammatory factors through miR-449a. Conclusion: Overexpression of TUSC7 inhibited microglial activation and the expression of inflammatory factors in microglia cells by regulating miR-449a/PPAR-gamma. (C) 2018 Elsevier Inc. All rights reserved.