Targeting lipid clearance pathways to promote repair after SCI

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PROJECT SUMMARY/ABSTRACT After spinal cord injury (SCI), the injury site is filled with cellular debris, especially myelin debris that creates a very unique lipid-dense environment. Macrophages are the predominant phagocyte that are responsible for debris-clearance, but this process is not only inefficient, it is also maladaptive. The excessive amount of myelin debris present at the injury site leads to formation lipid-laden macrophages (a.k.a. foamy macrophages) that become pro-inflammatory and contribute to tissue regeneration failure. Therefore, understanding the mechanisms of foamy macrophage formation after SCI may lead to novel therapeutic targets to promote repair after SCI. In this application, we will investigate the molecular mechanisms of lipid accumulation in foamy macrophages and how they contribute to fibrotic scar formation at the spinal cord injury site.