Repertoire of microglial and macrophage responses after spinal cord injury

Key Points Macrophages derived from the peripheral circulation and from resident microglia are among the main effectors of the inflammatory response after spinal cord injury. Activated macrophages/microglia in the injured spinal cord contribute to secondary tissue damage through generation of reactive oxygen species, the production of pro-inflammatory cytokines and other factors. Macrophages under certain conditions also seem to have beneficial properties in the injured CNS. Current understanding of macrophage polarization may provide better insights into why activated macrophages/microglia in the injured CNS have detrimental as well as beneficial properties. Studies in the field of infectious disease, tumour biology and other non-neural systems indicate that macrophages can be polarized to a 'classically' activated M1 cell that is pro-inflammatory and cytotoxic, or to an 'alternatively' activated M2 cell that is anti-inflammatory and has reparative properties. The microenvironment of the injured spinal cord favours polarization of M1 macrophages, with only a weak and transient M2 polarization. Understanding how to put the brake on M1 polarization and promote M2 polarization in the injured spinal cord may lead to the development of novel therapeutic approaches for treating spinal cord injury. Macrophages and microglia are major contributors to the inflammatory response that follows spinal cord trauma. Modulating the activation of these cells to harness their beneficial protective and reparative properties could be key for treating spinal cord injuries. Macrophages from the peripheral circulation and those derived from resident microglia are among the main effector cells of the inflammatory response that follows spinal cord trauma. There has been considerable debate in the field as to whether the inflammatory response is good or bad for tissue protection and repair. Recent studies on macrophage polarization in non-neural tissues have shed much light on their changing functional states. In the context of this literature, we discuss the activation of macrophages and microglia following spinal cord injury, and their effects on repair. Harnessing their anti-inflammatory properties could pave the way for new therapeutic strategies for spinal cord trauma.