Myelin as an inflammatory mediator: Myelin interactions with complement, macrophages, and microglia in spinal cord injury
While numerous studies have examined how macrophage activation states affect recovery after SCI (for a review see Gensel & Zhang, 2015), less is understood about how the lesion environment contributes to macrophage polarization. It is well established that myelin debris generated after SCI inhibits axonal regeneration and remyelination (McKerracher et al., 1994); however, myelin can also act as an inflammatory stimulus (Kroner et al., 2014; Wang et al., 2015; Williams, Ulvestad, Waage, Antel, & McLaurin, 1994). Lipid‐laden myelin debris is taken up and processed by inflammatory cells including neutrophils and macrophages. Myelin then becomes highly concentrated in these phagocytes, persisting in macrophages for weeks after SCI (Greenhalgh & David, 2014; Vargas & Barres, 2007; Wang et al., 2015). In addition, myelin initiates complement‐mediated inflammatory pathways with downstream effects on macrophage activation. This review focuses on the myelin–macrophage and complement neuroimmune interactions after SCI. Since myelin is ubiquitously present in the acute and chronically injured spinal cord, we will explore the mechanisms of myelin debris clearance and its downstream inflammatory effects.