Spinal cord injury: molecular mechanisms and therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 26, 2023

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

Language: Английский

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Progression in translational research on spinal cord injury based on microenvironment imbalance

Bone Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: April 8, 2022

Spinal cord injury (SCI) leads to loss of motor and sensory function below the level imposes a considerable burden on patients, families, society. Repair injured spinal has been recognized as global medical challenge for many years. Significant progress made in research pathological mechanism injury. In particular, with development gene regulation, cell sequencing, tracing technologies, in-depth explorations SCI microenvironment have become more feasible. However, translational studies related repair not yielded significant results. This review summarizes latest two aspects pathology: intraneuronal imbalance regenerative imbalance. We also strategies based imbalance, including medications, transplantation, exosomes, tissue engineering, reprogramming, rehabilitation. The current state future directions are discussed. combined, precise, multitemporal strategy repairing is potential direction.

Language: Английский

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Emerging role of STING signalling in CNS injury: inflammation, autophagy, necroptosis, ferroptosis and pyroptosis

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: Oct. 4, 2022

Abstract Stimulator of interferons genes (STING), which is crucial for the secretion type I and proinflammatory cytokines in response to cytosolic nucleic acids, plays a key role innate immune system. Studies have revealed participation STING pathway unregulated inflammatory processes, traumatic brain injury (TBI), spinal cord (SCI), subarachnoid haemorrhage (SAH) hypoxic–ischaemic encephalopathy (HIE). signalling markedly increased CNS injury, agonists might facilitate pathogenesis injury. However, effects STING-regulated activation are not well understood. Aberrant increases events, interferon responses, cell death. cGAS primary that induces activation. Herein, we provide comprehensive review latest findings related cGAS–STING highlight control mechanisms their functions Furthermore, summarize explore most recent advances toward obtaining an understanding involvement programmed death (autophagy, necroptosis, ferroptosis pyroptosis) during We also potential therapeutic agents capable regulating pathway, facilitates our value this as treatment target.

Language: Английский

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A reactive oxygen species-responsive hydrogel encapsulated with bone marrow derived stem cells promotes repair and regeneration of spinal cord injury

Bioactive Materials, Journal Year: 2022, Volume and Issue: 19, P. 550 - 568

Published: May 9, 2022

Spinal cord injury (SCI) is an overwhelming and incurable disabling event accompanied by complicated inflammation-related pathological processes, such as excessive reactive oxygen species (ROS) produced the infiltrated inflammatory immune cells released to extracellular microenvironment, leading widespread apoptosis of neuron cells, glial oligodendroctyes. In this study, a thioketal-containing ROS-scavenging hydrogel was prepared for encapsulation bone marrow derived mesenchymal stem (BMSCs), which promoted neurogenesis axon regeneration scavenging overproduced ROS re-building regenerative microenvironment. The could effectively encapsulate BMSCs, played remarkable neuroprotective role in vivo reducing production endogenous ROS, attenuating ROS-mediated oxidative damage downregulating cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6) tumor necrosis factor-alpha (TNF-α), resulting reduced cell spinal tissue. BMSCs-encapsulated also scar formation, improved tissue, thus distinctly enhanced motor functional recovery SCI rats. Our work provides combinational strategy against stress, with potential applications not only SCI, but other central nervous system diseases similar conditions.

Language: Английский

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ROS‐Scavenging Hydrogels Synergize with Neural Stem Cells to Enhance Spinal Cord Injury Repair via Regulating Microenvironment and Facilitating Nerve Regeneration

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(18)

Published: March 29, 2023

Abstract Although stem cell‐based therapy is recognized as a promising therapeutic strategy for spinal cord injury (SCI), its efficacy greatly limited by local reactive oxygen species (ROS)‐abundant and hyper‐inflammatory microenvironments. It still challenge to develop bioactive scaffolds with outstanding antioxidant capacity neural cells (NSCs) transplantation. In this study, albumin biomimetic cerium oxide nanoparticles (CeO 2 @BSA nanoparticles, CeNPs) are prepared in simple efficient manner dispersed gelatin methacryloyl obtain the ROS‐scavenging hydrogel (CeNP‐Gel). CeNP‐Gel synergistically promotes neurogenesis via alleviating oxidative stress microenvironments improving viability of encapsulated NSCs. More interestingly, presence CeNP‐Gel, microglial polarization anti‐inflammatory M2 subtype obviously facilitated, which further verified be associated phosphoinositide 3‐kinase/protein kinase B pathway activation. Additionally, injectable confirmed induce integration differentiation transplanted Compared blank‐gel group, survival rate NSCs group about 3.5 times higher, efficiency 2.1 higher. Therefore, NSCs‐laden represents comprehensive great application prospect treatment SCI through comprehensively modulating adverse microenvironment.

Language: Английский

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

ACS Nano, Journal Year: 2023, Volume and Issue: 17(18), P. 18562 - 18575

Published: Sept. 14, 2023

The treatment of spinal cord injury (SCI) remains unsatisfactory owing to the complex pathophysiological microenvironments at site and limited regenerative potential central nervous system. Metformin has been proven in clinical animal experiments repair damaged structures functions by promoting endogenous neurogenesis. However, early stage acute SCI, adverse microenvironment sites, such as reactive oxygen species inflammatory factor storm, can prevent activation neural stem cells (NSCs) differentiation NSCs into neurons, decreasing whole effect. To address those issues, a series robust multifunctional natural polyphenol-metformin nanoparticles (polyphenol-Met NPs) were fabricated with pH-responsiveness excellent antioxidative capacities. resulting NPs possessed several favorable advantages: First, composed active ingredients different biological properties, without need for carriers; second, feature could allow targeted drug delivery injured site; more importantly, enabled drugs performances exhibit strong synergistic effects. results demonstrated that improved polyphenols boosted activated neurons oligodendrocytes, which efficiently nerve enhance functional recovery SCI rats. This work highlighted design fabrication via efficient microenvironmental regulation activation.

Language: Английский

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Multifunctional Conductive and Electrogenic Hydrogel Repaired Spinal Cord Injury via Immunoregulation and Enhancement of Neuronal Differentiation

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(21)

Published: Feb. 3, 2024

Abstract Spinal cord injury (SCI) is a refractory neurological disorder. Due to the complex pathological processes, especially secondary inflammatory cascade and lack of intrinsic regenerative capacity, it difficult recover function after SCI. Meanwhile, simulating conductive microenvironment spinal reconstructs electrical neural signal transmission interrupted by SCI facilitates repair. Therefore, double‐crosslinked hydrogel (BP@Hydrogel) containing black phosphorus nanoplates (BP) synthesized. When placed in rotating magnetic field (RMF), BP@Hydrogel can generate stable signals exhibit electrogenic characteristic. In vitro, shows satisfactory biocompatibility alleviate activation microglia. RMF, enhances anti‐inflammatory effects. wireless stimulation promotes differentiation stem cells (NSCs) into neurons, which associated with PI3K/AKT pathway. vivo, injectable elicit behavioral electrophysiological recovery complete transected mice alleviating inflammation facilitating endogenous NSCs form functional neurons synapses under RMF. The present research develops multifunctional for repair targeting multiple mechanisms including immunoregulation enhancement neuronal differentiation.

Language: Английский

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Axon-like aligned conductive CNT/GelMA hydrogel fibers combined with electrical stimulation for spinal cord injury recovery

Bioactive Materials, Journal Year: 2024, Volume and Issue: 35, P. 534 - 548

Published: Feb. 22, 2024

Rehabilitation and regenerative medicine are two promising approaches for spinal cord injury (SCI) recovery, but their combination has been limited. Conductive biomaterials could bridge scaffolds with electrical stimulation by inducing axon regeneration supporting physiological signal transmission. Here, we developed aligned conductive hydrogel fibers incorporating carbon nanotubes (CNTs) into methacrylate acylated gelatin (GelMA) via rotating liquid bath electrospinning. The electrospun CNT/GelMA mimicked the micro-scale structure, conductivity, soft mechanical properties of neural axons. For

Language: Английский

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Urolithin A alleviates NLRP3 inflammasome activation and pyroptosis by promoting microglial mitophagy following spinal cord injury

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114057 - 114057

Published: Jan. 18, 2025

Language: Английский

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TLR4 promotes microglial pyroptosis via lncRNA-F630028O10Rik by activating PI3K/AKT pathway after spinal cord injury

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(8)

Published: Aug. 10, 2020

Abstract Neuroinflammation plays a crucial role in the secondary phase of spinal cord injury (SCI), and is initiated following activation toll-like receptor 4 (TLR4). However, downstream mechanism remains unknown. Pyroptosis form inflammatory programmed cell death, which closely involved neuroinflammation, it can be regulated by TLR4 according to recent research. In addition, several studies have shown that long non-coding RNAs (lncRNAs) based mechanisms were related signal transduction regulation inflammation. Thus, this study, we want determine whether regulate pyroptosis after SCI via lncRNAs. Our results showed was activated promoted expression lncRNA-F630028O10Rik. This lncRNA functioned as ceRNA for miR-1231-5p/Col1a1 axis enhanced microglial activating PI3K/AKT pathway. Furthermore, determined STAT1 upstream transcriptional factor IncRNA-F630028O10Rik induced damage-responsive TLR4/MyD88 signal. findings provide new insights novel therapeutic strategy treating SCI.

Language: Английский

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