Macrophage phagocytosis after spinal cord injury: when friends become foes

After spinal cord injury, macrophages can exert either beneficial or detrimental effects depending on their phenotype. Aside from their critical role in inflammatory responses, macrophages are also specialized in the recognition, engulfment, and degradation of pathogens, apoptotic cells, and tissue debris. They promote remyelination and axonal regeneration by removing inhibitory myelin components and cellular debris. However, excessive intracellular presence of lipids and dysregulated intracellular lipid homeostasis result in the formation of foamy macrophages. These develop a pro-inflammatory phenotype that may contribute to further neurological decline. Additionally, myelin-activated macrophages play a crucial role in axonal dieback and retraction. Here, we review the opposing functional consequences of phagocytosis by macrophages in spinal cord injury, including remyelination and regeneration versus demyelination, degeneration, and axonal dieback. Furthermore, we discuss how targeting the phagocytic ability of macrophages may have therapeutic potential for the treatment of spinal cord injury.