Altering Macrophages to Improve Neuroprotection after Spinal Cord Injury

Abstract The goal of this application is boost the intrinsic ability of macrophages to remove dead/dying cells and growth-inhibitory molecules from the site of spinal cord injury (SCI) without concurrently activating neurotoxic pro-inflammatory signaling pathways. By doing so, less secondary tissue damage is expected at the injury site concomitant with enhanced growth or plasticity of axons and improved functional recovery. We predict that this can be accomplished through overexpression of the triggering receptor expressed on myeloid cells (TREM)-2. We have developed a lentiviral vector system for overexpressing TREM2 on cells. The goal of this propsal is to test the gene specificity of the new construct, conduct optimization experiments with different macrophage cell lines, and phenotype cells expressing the transgene. From these experiments we hope to generate preliminary data for grants focused on modifying macrophage phenotype in aged models of SCI.