Problems and challenges in regeneration and repair of spinal cord injury

BACKGROUND: Spinal cord injury leads to severe sensory and motor dysfunctions, abnormal reflexes, and autonomic nerve disorders. At present, there are no effective clinical therapies for spinal cord injury. In recent years, researchers have developed a variety of novel approaches, opening up new avenues for clinical treatment of spinal cord injury. OBJECTIVE: To characterize the pathophysiological process of spinal cord injury, summarize recent advances in regeneration and repair of spinal cord injury, analyze the current status and challenges with respect to clinical translation, and consider the future development trend for treatment of spinal cord injury. METHODS: The relevant articles were searched in PubMed database from 2003 to 2020 using the key words of “spinal cord injury, neuroplasticity, functional recovery, therapeutic strategy, combinatory therapies, clinical translation”. 398 articles were initially retrieved. After sorting and screening, 116 articles were eventually included for analysis and summary. RESULTS AND CONCLUSION: The pathophysiology of spinal cord injury involves primary injury and secondary injury. Targeting the pathophysiology of spinal cord injury, the potential therapeutic strategies for spinal cord injury include (1) enhance neuroprotection: reduction of secondary injury; (2) promote regenerative repair: activate the intrinsic regenerative capacity of neurons, ameliorate microenvironment, cell transplantation, neuromodulation and rehabilitation, brain-machine interface, and combinatory therapies. The pathological process of spinal cord injury is very complicated, and individual treatment is insufficient to promote nerve regeneration and functional recovery after spinal cord injury in humans. Combinatory strategies have demonstrated greater beneficial outcomes than individual treatment by addressing multiple aspects of spinal cord injury pathology. Clinical trials in the future should strengthen multidisciplinary conversation and cooperation, to determine the optimal combinatory approaches, promoting functional recovery of patients with spinal cord injury.