The Key Role of Macrophages and Monocytes in Spinal Cord Injury: Development of Novel Therapeutic Approaches

Spinal cord injury (SCI) causes inflammation by activating innate immune responses. The process of secondary spinal cord injury involves oligodendrocyte apoptosis, myelin sheath degradation, axonal degeneration, and nerve cell death. The inflammatory microenvironment created by SCI affects nerve repair and recovery. In SCI, macrophage activation, accumulation, and persistent inflammation occur. Macrophages are heterogeneous cells with variable and extensive functions that some of their phenotypes play an important role in decreasing post-nerve injury recovery. After neurodegeneration, resident and peripheral immune cell-derived microglia participate in the inflammatory process and upregulate inflammatory cytokines. Other important issues include the role of monocytes as a source of macrophages in the process of spinal cord injury. Understanding the aspect and function of these cells can be helpful to design novel therapeutic strategies.

Rapid infiltration of leukocytes into the injured spinal cord is involved in the pathogenesis of secondary spinal cord injury. Therapeutic approaches to inhibit leukocyte infiltration into the injured site enhance the recovery of nerve and white matter injuries after SCI. The first cells to invade the spinal cord are monocytes and neutrophils. Monocytes are the source of cytokines, inflammatory chemokines, and oxidative stress that infiltrate the injured site within the first 24 hours after SCI and reach their peak within 4 to 7 days after injury. This article reviews the different roles of macrophages and monocytes and their potential impacts in adopting novel therapeutic approaches in patients with SCI.