![]() ![]() We summarize the recent progress regarding interventions after SCI in preclinical rodent and non-human primate models as well as in the clinical settings. In this review, we provide an overview of recent advances and challenges in SCI research and treatment. However, relatively few inventions have been completed due to lack of clinical efficacy. These strategies have shown promising results in preclinical studies, and some have entered phase 1 or 2 clinical trials. In recent years, owing to the development of novel molecular biology, materials science, genetic engineering, and computer science approaches, researchers have developed a variety of novel therapeutic concepts to treat SCI, including tissue engineering, gene editing, and neuromodulation technology. Axon regeneration and functional recovery after SCI remains one of the most challenging medical problems in the field of neuroscience. Unfortunately, the clinical benefit achieved using current approaches is limited and there are no effective strategies currently existing to repair SCI, thus patients suffer long-term dysfunction and lifelong disability. The current clinical treatment for SCI mainly includes early surgical decompression and stabilization, augmentation of spinal cord perfusion, intravenous administration of high-dose corticosteroids, anti-inflammatory therapy in the acute phase, and neurological rehabilitation training during the chronic phase ( Karsy and Hawryluk, 2019). The secondary injury references the consecutive pathological events triggered by the primary injury, such as hemorrhage, excitotoxicity, neuroinflammation, demyelination, astrogliosis and extracellular matrix (ECM) remodeling, which aggravate tissue damage, and compromise neuroplasticity ( Rowland et al., 2008). The primary injury is caused by acute mechanical trauma and results in vascular disruption, blood–spinal cord barrier rupture, cell death (neurons, glia cells, and endothelial cells), and interruption of neural fiber tracts in the spinal cord. ![]() ![]() The pathophysiology of SCI involves primary injury and secondary injury. Therefore, effective treatments are urgently needed to cure individuals with SCI. SCI not only seriously affects the quality of life and life span of patients, but it also leads to psychological and emotional disorders and social phobia, with enormous impact and heavy economic burden on the family as well as the social health care system ( Alizadeh et al., 2019). SCI interrupts the neural connections between the upper center and the spinal cord, leading to devastating and permanent neurological impairment, including sensory and motor disability, abnormal reflexes, and autonomic disorders ( Ehrmann et al., 2020 Ong et al., 2020). There are hundreds of thousands of new patients suffering an SCI each year worldwide, and ninety percent of these SCIs are caused by traumatic events, including traffic accidents, falling, sports injuries, violence, etc. Spinal cord injury (SCI) leads to long-term dysfunction and lifelong disability. Going forward, clinical trials should emphasize multidisciplinary conversation and cooperation to identify optimal combinatorial approaches to maximize therapeutic benefit in humans with SCI. Finally, we consider the future of SCI treatment and provide insights into how to narrow the translational gap that currently exists between preclinical studies and clinical practice. In addition, we analyze the current status, remaining problems, and realistic challenges towards clinical translation. In this review, we characterize the mechanisms underlying axon regeneration of adult neurons and summarize recent advances in facilitating functional recovery following SCI at both the acute and chronic stages. Although many problems and challenges remain, the encouraging outcomes that have been achieved in preclinical models offer a promising foothold for the development of novel clinical strategies to treat SCI. Combinatory strategies targeting multiple aspects of SCI pathology have achieved greater beneficial effects than individual therapy alone. The pathophysiology of SCI is complicated and multifaceted, and thus individual treatments acting on a specific aspect or process are inadequate to elicit neuronal regeneration and functional recovery after SCI. Spinal cord injury (SCI) disrupts the structural and functional connectivity between the higher center and the spinal cord, resulting in severe motor, sensory, and autonomic dysfunction with a variety of complications. ![]()
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