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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Exosome-mediated delivery and regulation in neurological disease progression

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 264, P. 130728 - 130728

Published: March 11, 2024

Exosomes (EXOs), minute membranous structures originating from diverse biological sources, have recently seized the attention of researchers due to their theranostic potential for neurological diseases. Released actively by various cells, including stem adipose tissue, and immune EXOs wield substantial regulatory influence over intricate landscape complications, exhibiting both positive negative modulatory effects. In AD, play a pivotal role in disseminating breaking down amyloid-β protein. Moreover, derived mesenchymal cells showcase remarkable capacity mitigate pro-inflammatory phenotypes regulating miRNAs neurodegenerative These vesicles possess unique ability traverse blood-brain barrier, governing aggregation mutant huntingtin Understanding exosomal functions within CNS holds significant promise enhancing treatment efficacy This review intricately examines mechanisms involving disease development, highlighting therapeutic prospects exploring utility exosome-based nanomedicine complications. Additionally, delves into challenges associated with drug delivery brain, emphasizing complexities inherent this critical aspect neurotherapeutics.

Language: Английский

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Engineering strategies and optimized delivery of exosomes for theranostic application in nerve tissue

Theranostics, Journal Year: 2023, Volume and Issue: 13(12), P. 4266 - 4286

Published: Jan. 1, 2023

Severe injuries or diseases affecting the peripheral and central nervous systems can result in impaired organ function permanent paralysis.Conventional interventions, such as drug administration cell-based therapy, exhibit limited effectiveness due to their inability preserve post-implantation cell survival impede deterioration of adjacent tissues.Exosomes have recently emerged powerful tools for tissue repair owing proteins nucleic acids, well unique phospholipid properties, which facilitate targeted delivery recipient cells.Engineering exosomes, obtained by manipulating parental cells directly functionalizing play critical roles enhancing regenerative repair, reducing inflammation, maintaining physiological homeostasis.Furthermore, exosomes been shown restore neurological when used combination with biomaterials.This paper primarily focuses on engineering strategies routes related neural research emphasizes theranostic application optimized nerve, traumatic spinal cord, brain injuries.Finally, prospects development other approaches will be discussed enhance our knowledge diseases.

Language: Английский

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Microglia-derived exosomes modulate myelin regeneration via miR-615-5p/MYRF axis

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Jan. 22, 2024

Abstract Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number neurological disorders. Spontaneous demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present demyelinated lesions abundance, mostly fail to differentiate into oligodendrocytes, myelinating CNS. In addition OPCs, assembled numbers activated resident microglia/infiltrated macrophages; however, mechanisms potential role interactions between microglia/macrophages OPCs poorly understood. Here, we generated transcriptional profile exosomes from microglia, found that miR-615-5p was elevated. bound 3′UTR myelin regulator factor (MYRF), crucial myelination transcription expressed lineage cells. Mechanistically, microglia transferred directly MYRF inhibited OPC maturation. Furthermore, an effect AAV expressing sponge tested experimental autoimmune encephalomyelitis (EAE) cuprizone (CPZ)-induced demyelination model, classical mouse models multiple sclerosis. effectively alleviated disease progression promoted remyelination. This study identifies miR-615-5p/MYRF new target for therapy diseases.

Language: Английский

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G-quadruplex-guided cisplatin triggers multiple pathways in targeted chemotherapy and immunotherapy

Chemical Science, Journal Year: 2024, Volume and Issue: 15(25), P. 9756 - 9774

Published: Jan. 1, 2024

PyPDSplatins can not only bind G4s to repress c-MYC and VEGF expressions but also damage activate the immune-related cGAS-STING pathway AIM2-ASC-related pyroptosis, triggering a strong immune response potent antitumor effects.

Language: Английский

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Extracellular Vesicles as Mediators of Neuroinflammation in Intercellular and Inter-Organ Crosstalk

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7041 - 7041

Published: June 27, 2024

Neuroinflammation, crucial in neurological disorders like Alzheimer's disease, multiple sclerosis, and hepatic encephalopathy, involves complex immune responses. Extracellular vesicles (EVs) play a pivotal role intercellular inter-organ communication, influencing disease progression. EVs serve as key mediators the system, containing molecules capable of activating molecular pathways that exacerbate neuroinflammatory processes disorders. However, from mesenchymal stem cells show promise reducing neuroinflammation cognitive deficits. can cross CNS barriers, peripheral signals influence brain function via EV-mediated impacting barrier Understanding EV interactions within other organs could unveil novel therapeutic targets for

Language: Английский

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Taxifolin attenuates neuroinflammation and microglial pyroptosis via the PI3K/Akt signaling pathway after spinal cord injury

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 114, P. 109616 - 109616

Published: Dec. 22, 2022

Language: Английский

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A swift expanding trend of extracellular vesicles in spinal cord injury research: a bibliometric analysis

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 23, 2023

Abstract Extracellular vesicles (EVs) in the field of spinal cord injury (SCI) have garnered significant attention for their potential applications diagnosis and therapy. However, no bibliometric assessment has been conducted to evaluate scientific progress this area. A search articles Web Science (WoS) from January 1, 1991, May 2023, yielded 359 papers that were analyzed using various online analysis tools. These cited 10,842 times with 30.2 per paper. The number publications experienced explosive growth starting 2015. China United States led research initiative. Keywords divided into 3 clusters, including “Pathophysiology SCI”, “Bioactive components EVs”, “Therapeutic effects EVs SCI”. By integrating average appearing year (AAY) keywords VoSviewer time zone map Citation Explosion CiteSpace, focal point undergone a transformative shift. emphasis moved away pathophysiological factors such as “axon”, “vesicle”, “glial cell” more mechanistic applied domains “activation”, “pathways”, “hydrogels” “therapy”. In conclusions, institutions are expected allocate resources towards EVs-loaded hydrogel therapy utilization innovative materials mitigation.

Language: Английский

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Neurotrauma—From Injury to Repair: Clinical Perspectives, Cellular Mechanisms and Promoting Regeneration of the Injured Brain and Spinal Cord

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 643 - 643

Published: March 13, 2024

Traumatic injury to the brain and spinal cord (neurotrauma) is a common event across populations often causes profound irreversible disability. Pathophysiological responses trauma exacerbate damage of an index injury, propagating loss function that central nervous system (CNS) cannot repair after initial resolved. The way in which lost consequence complex array mechanisms continue chronic phase post-injury prevent effective neural repair. This review summarises events traumatic (TBI) (SCI), comprising description current clinical management strategies, summary known cellular molecular secondary their role prevention A discussion emerging approaches promote neuroregeneration CNS presented. barriers promoting neurotrauma are pathways cell types occur on level. presents challenge traditional pharmacological targeting single pathways. It suggested novel multiple or using combinatorial therapies may yield sought-after recovery for future patients.

Language: Английский

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Crosstalk Between Cell Death and Spinal Cord Injury: Neurology and Therapy

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(12), P. 10271 - 10287

Published: May 7, 2024

Language: Английский

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