Spinal cord injury: molecular mechanisms and therapeutic interventions

Abstract

Spinal cord injury (SCI) remains a severe condition with an extremely high disability rate. The challenges of SCI repair include its complex pathological mechanisms and the difficulties of neural regeneration in the central nervous system. In the past few decades, researchers have attempted to completely elucidate the pathological mechanism of SCI and identify effective strategies to promote axon regeneration and neural circuit remodeling, but the results have not been ideal. Recently, new pathological mechanisms of SCI, especially the interactions between immune and neural cell responses, have been revealed by single-cell sequencing and spatial transcriptome analysis. With the development of bioactive materials and stem cells, more attention has been focused on forming intermediate neural networks to promote neural regeneration and neural circuit reconstruction than on promoting axonal regeneration in the corticospinal tract. Furthermore, technologies to control physical parameters such as electricity, magnetism and ultrasound have been constantly innovated and applied in neural cell fate regulation. Among these advanced novel strategies and technologies, stem cell therapy, biomaterial transplantation, and electromagnetic stimulation have entered into the stage of clinical trials, and some of them have already been applied in clinical treatment. In this review, we outline the overall epidemiology and pathophysiology of SCI, expound on the latest research progress related to neural regeneration and circuit reconstruction in detail, and propose future directions for SCI repair and clinical applications.

The “Inner–Outer” Molecules-Loaded Fiber-Hydrogel Scaffolds Coordinate Specific Immunity and Neural Differentiation for Repairing SCI

“…T cells infiltrate the injured site early in SCI, tending to exacerbate the inflammatory response after SCI . It has been shown that the absence of T cells or the application of immunosuppressive agents is associated with improved function preservation after SCI. , However, the administration of T cells is frequently an overlooked target in SCI treatment strategies.…”

“…It has been shown that the absence of T cells or the application of immunosuppressive agents is associated with improved function preservation after SCI. , However, the administration of T cells is frequently an overlooked target in SCI treatment strategies. Considering that specific autoimmunity is detrimental to neurological recovery, it may be crucial to modulate specific immunity in early stages of SCI that the activation of T cells is regulated to diminish their ability to exert biological effects.…”

In Situ Reaction-Generated Aldehyde-Scavenging Polypeptides-Curcumin Conjugate Nanoassemblies for Combined Treatment of Spinal Cord Injury

“…In the secondary injury of SCI, inflammation and oxidative stress as two pivotal cascades have been extensively documented. − Soon after the primary injury, resident microglia are activated and immune cells including neutrophils and monocytes as well as macrophages are also recruited and infiltrated into the lesion sites . Along with this, the inflammatory factors are oversecreted and the hyper inflammatory reactions occurred .…”

TP53INP2 knockdown inhibits inflammatory response and apoptosis after spinal cord injury

“…Surveys conducted by the World Health Organization have shown that the annual global incidence of SCI is 40–80 cases per million people 2 . SCI is mainly caused by vertebral body displacement or protrusion of bone fragments into the spinal canal due to traffic accidents, fall injuries, falls, or trauma, resulting in varying degrees of damage to the spinal cord or cauda equina 3 . Spinal cord injury can cause pathological changes, such as neuronal apoptosis, neuroinflammation, and oxidative stress 3 .…”

“…SCI is mainly caused by vertebral body displacement or protrusion of bone fragments into the spinal canal due to traffic accidents, fall injuries, falls, or trauma, resulting in varying degrees of damage to the spinal cord or cauda equina 3 . Spinal cord injury can cause pathological changes, such as neuronal apoptosis, neuroinflammation, and oxidative stress 3 . However, the ability of nerves to self‐repair is limited, and the efficacy of various treatments applied to repair nerves after spinal cord injury, such as neuroprotective and neuroregenerative therapies, is unsatisfactory 4,5 .…”