Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications
Hassan Saad
Bachar El Baba
Ali Tfaily
Firas Kobeissy
Juanmarco Gutierrez Gonzalez
Daniel Refai
Gerald R.Rodts
Christian Mustroph
David Gimbel
Jonathan Grossberg
Daniel L.Barrow
Matthew F.Gary
Ali M.Alawieh
Abstract：Spinal cord injury remains a major cause of disability in young adults, and beyond acute decompression and rehabilitation, there are no pharmacological treatments to limit the progression of injury and optimize recovery in this population. Following the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation, a similar role for complement in spinal neuroinflammation is a focus of ongoing research. In this work, we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins, triggers of complement activation, and role of effector functions in the pathology. We study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris, and/or activation via antibody binding to damage-associated molecular patterns. Several effector functions of complement have been implicated in spinal cord injury, and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord injury. Following this pathophysiological review, we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human subjects. This review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury, to evaluate the phases of involvement of opsonins and anaphylatoxins, and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.
Keywords：complementneuroinflammationneuroplasticityregenerationspinal cord injurytargeted therapy
Publication Date：2025-05-27
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：12( 1324-1335 )