Diogo Nascimento, Ana Ferreira, Célia Duarte Cruz
Spinal cord injury (SCI) poses a substantial physical, psychological and social burden. Although many therapies are currently available, it is still impossible to fully restore the lost organic functions of SCI patients. An important event in SCI physiopathology is the development of a neuron-repulsive fibrotic scar at the lesion site, a barrier that hampers neuronal growth and contributes to long-term functional impairment. This neuron-repulsive scar is present in severe spinal cord injuries in humans but is absent in some animals capable of natural regeneration. In humans and other mammals, various immune cells take part in the development and maturation of the glial scar, and cytokines and other molecular factors regulate the associated histologic changes. Pro-inflammatory cytokines and complement system proteins tend to be overexpressed early after SCI, but anti-inflammatory cytokines also participate in the remodelling of the injured tissue by regulating the excessively pro-inflammatory environment. This inflammatory regulation is not entirely successful in humans, and inflammation inhibitor drugs offer promising avenues for SCI treatment. Some non-specific immunosuppressor drugs have already been studied, but targeted modulation therapies may be more efficient and less prone to secondary effects. Continued experimental research and clinical trials are vital to advance findings and develop effective treatments, aiming to overcome the barriers to spinal cord regeneration and improve recovery for SCI patients.