Fibrotic Scars and the Potential Therapeutics After Spinal Cord Injury

Spinal cord injury (SCI) affects millions of people worldwide, resulting in persistent direct and secondary effects including but not limited to motor, sensory, and autonomic dysfunction. The widespread nature of this condition, as well as its detrimental effects, makes recovery following SCI an important clinical problem. One primary issue identified in SCI among other neurological conditions is fibrotic scarring, as its dynamic nature provides both beneficial and detrimental effects over its developmental course. Initially, early scar formation contributes to wound closure and tissue stabilization, but chronic, persistent fibrosis later interferes with axonal growth and other neural repair mechanisms. The scar itself is highly dynamic, consisting of components including collagens, fibronectin, proteoglycans, and laminins, all of which have diverse localization and functionality throughout scar maturation. Its formation is regulated by various signaling mechanisms, including inflammatory signaling, profibrotic pathways, vascular responses, interactions between fibroblasts and neighboring cells, and changes in the specific mechanical environment of the injury site. This review focuses primarily on SCI, with findings from additional central nervous system injury and disease models used to provide a holistic, clinically relevant overview of fibrotic scar organization, profibrotic signaling, and potential therapeutic targets.