Complement and spinal cord injury: Traditional and non-traditional aspects of complement cascade function in the injured spinal cord microenvironment

• The inflammatory complement system is activated in the spinal cord following injury.
• Complement mediates inflammatory cell recruitment and debris removal after SCI.
• Non-traditional functions for complement in other models are relevant for SCI.

The pathology associated with spinal cord injury (SCI) is caused not only by primary mechanical trauma, but also by secondary responses of the injured CNS. The inflammatory response to SCI is robust and plays an important but complex role in the progression of many secondary injury-associated pathways. Although recent studies have begun to dissect the beneficial and detrimental roles for inflammatory cells and proteins after SCI, many of these neuroimmune interactions are debated, not well understood, or completely unexplored. In this regard, the complement cascade is a key component of the inflammatory response to SCI, but is largely underappreciated, and our understanding of its diverse interactions and effects in this pathological environment is limited. In this review, we discuss complement in the context of SCI, first in relation to traditional functions for complement cascade activation, and then in relation to novel roles for complement proteins in a variety of models.