Restoration of spinal cord injury: From endogenous repairing process to cellular therapy

Abstract

Spinal cord injury (SCI) disrupts neurological pathways and impacts sensory, motor, and autonomic nerve function. There is no effective treatment for SCI currently. Numerous endogenous cells, including astrocytes, macrophages/microglia, and oligodendrocyte, are involved in the histological healing process following SCI. By interfering with cells during the SCI repair process, some advancements in the therapy of SCI have been realized. Nevertheless, the endogenous cell types engaged in SCI repair and the current difficulties these cells confront in the therapy of SCI are poorly defined, and the mechanisms underlying them are little understood. In order to better understand SCI and create new therapeutic strategies and enhance the clinical translation of SCI repair, we have comprehensively listed the endogenous cells involved in SCI repair and summarized the six most common mechanisms involved in SCI repair, including limiting the inflammatory response, protecting the spared spinal cord, enhancing myelination, facilitating neovascularization, producing neurotrophic factors, and differentiating into neural/colloidal cell lines.

Caffeic acid phenethyl ester inhibits neuro-inflammation and oxidative stress following spinal cord injury by mitigating mitochondrial dysfunction via the SIRT1/PGC1α/DRP1 signaling pathway

“…Many studies have shown that microglia-mediated neuro-inflammation and oxidative stress induce the release of neurotoxic substances, produce excessive glial scarring, and inhibit axon regeneration, which aggravate nerve tissue damage after SCI. This damage directly affects the recovery of motor function [ 60 , 61 ]. In order to visually explore the therapeutic effect of CAPE after SCI, we continuously injected CAPE intraperitoneally into SCI mice and observed changes in nerve tissue structure and functional motor recovery.…”

Biomaterials targeting the microenvironment for spinal cord injury repair: progression and perspectives

“…CSPGs are synthesized by several cell types, including astrocytes, fibroblasts, and macrophages, and are known to significantly influence fibrosis and wound healing. CSPGs serve as a substrate that facilitates fibroblast aggregation, potentially leading to increased fibrosis and scarring ( Wu et al, 2022 ). Currently, the degradation of CSPGs involves the use of ARSB, which selectively inhibits the presence of 4-CS sulfate (C4S) glycosaminoglycans (GAGs) in the sugar chain of CSPGs ( Pearson et al, 2018 ).…”

“…In an acute stage, the primary SCI initiates a multifaceted cascade of pathogenic changes, including hemorrhage, cellular damage, oxidative stress, axonal degeneration, and necrosis. Such changes lead to loss of neural tissues and over-production of inflammatory cytokines ( Wu et al, 2022 ). In the following phases, host cells around the lesion respond to cytokines to remove cellular debris and initiate cellular proliferate that will confine the lesion.…”

Activity based restorative therapy considerations for children: medical and therapeutic perspectives for the pediatric population

“…There is increased focus on provided stimulation below the level of injury to optimize the nervous system for recovery and enhance the physical integrity of the body ( 7 ). This prepares the nervous system for recovery by mobilizing the endogenous cells, who work to repair and remyelinate ( 8 ). Interventions such as functional electrical stimulation, range of motion, and weight bearing all aid in maintaining bone mass, muscle health, and tendon length while offsetting the rapid aging and deterioration that people with spinal cord injury experience.…”