Recent progress and challenges in the treatment of spinal cord injury

Abstract

Spinal cord injury (SCI) disrupts the structural and functional connectivity between the higher centre and the spinal cord, resulting in severe motor, sensory, and autonomic dysfunction with a variety of complications. 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. Combinatory strategies targeting multiple aspects of SCI pathology have achieved greater beneficial effects than individual therapy alone. 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. 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. In addition, we analyze the current status, remaining problems, and realistic challenges towards clinical translation. 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. Going forward, clinical trials should emphasize multidisciplinary conversation and cooperation to identify optimal combinatorial approaches to maximize therapeutic benefit in humans with SCI.

Advance in pediatric spinal cord injury

“…5,6 The excessive activation of excitatory amino acid receptors produces excitotoxicity and further expands the loss of neurons and glial cells through necrosis and apoptotic cell death. 7 This chain of events enlarges the area of nerve tissue injury and worsens the neurological function defect and prognosis. 8,9 Furthermore, there are numerous variables that impede nerve regeneration following a spinal cord injury.…”

“…Finally, due to the release of damaged cells, excitatory amino acids (glutamic acid and aspartic acid) increase 5,6 . The excessive activation of excitatory amino acid receptors produces excitotoxicity and further expands the loss of neurons and glial cells through necrosis and apoptotic cell death 7 . This chain of events enlarges the area of nerve tissue injury and worsens the neurological function defect and prognosis 8,9 …”

Robust and Multifunctional Nanoparticles Assembled from Natural Polyphenols and Metformin for Efficient Spinal Cord Regeneration

“…Spinal cord injury (SCI) is a destructive neuropathological disease of neural circuitry and connectivity caused by external violence, tumor, and other factors, leading to loss of autonomic regulation, intestinal dysfunction, and permanent sensory and motor dysfunction. − After SCI caused by primary violence, a harsh microenvironment caused by oxidative stress and neuroinflammation storms usually plays a dominant role in the subsequent injury, including neuron loss, demyelination, and axon dieback, which further exacerbates neurological dysfunction. ,, Inhibiting the release of pro-inflammatory factors and effectively removing reactive oxygen species (ROS) after the injury have been regarded as an efficient way to reduce neuronal apoptosis and axon demyelination, achieving excellent neuroprotective effects. − However, the harsh microenvironment at the injury site has limited potential to mobilize the innate regeneration of the spinal cord, which cannot achieve satisfactory results in repairing damaged structures and promoting the recovery of motor function in SCI animal models. , Therefore, given the limited regenerative capability after SCI, the strategy of simply remodeling the harsh microenvironment after injury may not promote significant neural regeneration and function restoration efficiently, and further considerations are highly desirable to address the challenge.…”

“…4−7 However, the harsh microenvironment at the injury site has limited potential to mobilize the innate regeneration of the spinal cord, which cannot achieve satisfactory results in repairing damaged structures and promoting the recovery of motor function in SCI animal models. 2,8 Therefore, given the limited regenerative capability after SCI, the strategy of simply remodeling the harsh microenvironment after injury may not promote significant neural regeneration and function restoration efficiently, and further considerations are highly desirable to address the challenge.…”

Multifunctional Hierarchical Nanoplatform with Anisotropic Bimodal Mesopores for Effective Neural Circuit Reconstruction after Spinal Cord Injury

“…Traumatic spinal cord injury (SCI) is one of the most frequent and devastating diseases in orthopedics, causing permanent loss of motor control and autonomic dysfunction. − The initial mechanical injury triggers axonal dissection and neuronal death, while a secondary cascade of inflammatory responses leads to a localized increase in oxidative stress, further amplifying the process. − Preserving neurons and rebuilding neural circuits are crucial for the restoration of neurological function. ,, However, the current clinical therapies for traumatic SCI have limited therapeutic efficacy due to the following reasons: (i) Cascading inflammatory response leading to persistent occurrence of reactive oxygen species (ROS)-induced neuronal apoptosis and axonal degeneration; (ii) Limited intrinsic axonal regeneration capacity in adult mammalian neurons; (iii) Exogenous inhibitory factors impeding the elongation of axons across the injury site and the reestablishment of functional connectivity. − Given the multifaceted nature of SCI, it is essential to develop a combination therapy to effectively address the multiple barriers to nerve regeneration.…”