Moving beyond the glial scar for spinal cord repair

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Aug. 28, 2019

Abstract Traumatic spinal cord injury results in severe and irreversible loss of function. The triggers a complex cascade inflammatory pathological processes, culminating formation scar. While traditionally referred to as glial scar, the scar fact comprises multiple cellular extracellular components. This multidimensional nature should be considered when aiming understand role scarring limiting tissue repair recovery. In this Review we discuss recent advances understanding composition phenotypic characteristics oversimplification defining binary terms good or bad, development therapeutic approaches target components enable improved functional outcome after injury.

Language: Английский

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Astrocyte Reactivity: Subtypes, States, and Functions in CNS Innate Immunity

Trends in Immunology, Journal Year: 2020, Volume and Issue: 41(9), P. 758 - 770

Published: Aug. 17, 2020

Astrocytes are neural parenchymal cells that ubiquitously tile the central nervous system (CNS). In addition to playing essential roles in healthy tissue, astrocytes exhibit an evolutionarily ancient response all CNS insults, referred as astrocyte reactivity. Long regarded passive and homogeneous, reactivity is being revealed a heterogeneous functionally powerful component of mammalian innate immunity. Nevertheless, concepts about what comprises it does incomplete sometimes controversial. This review discusses goal differentiating reactive subtypes states based on composite pictures molecular expression, cell morphology, cellular interactions, proliferative state, normal functions, disease-induced dysfunctions. A working model conceptual framework presented for characterizing diversity

Language: Английский

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Required growth facilitators propel axon regeneration across complete spinal cord injury

Nature, Journal Year: 2018, Volume and Issue: 561(7723), P. 396 - 400

Published: Aug. 28, 2018

Language: Английский

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Spinal cord repair: advances in biology and technology

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(6), P. 898 - 908

Published: June 1, 2019

Language: Английский

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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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The translational landscape in spinal cord injury: focus on neuroplasticity and regeneration

Nature Reviews Neurology, Journal Year: 2019, Volume and Issue: 15(12), P. 732 - 745

Published: Nov. 14, 2019

Language: Английский

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Questions and (some) answers on reactive astrocytes

Glia, Journal Year: 2019, Volume and Issue: 67(12), P. 2221 - 2247

Published: Aug. 19, 2019

Abstract Astrocytes are key cellular partners for neurons in the central nervous system. react to virtually all types of pathological alterations brain homeostasis by significant morphological and molecular changes. This response was classically viewed as stereotypical is called astrogliosis or astrocyte reactivity. It long considered a nonspecific, secondary reaction conditions, offering no clues on disease‐causing mechanisms with little therapeutic value. However, many studies over last 30 years have underlined crucial active roles played astrocytes physiology, ranging from metabolic support, synapse maturation, pruning fine regulation synaptic transmission. prompted researchers explore how these new functions were changed disease, they reported them (sometimes beneficial, mostly deleterious). More recently, cell‐specific transcriptomics revealed that undergo massive changes gene expression when become reactive. observation further stressed reactive may be very different normal, nonreactive could influence disease outcomes. To make picture even more complex, both normal shown molecularly functionally heterogeneous. Very known about specific each subtype play contexts. In this review, we interrogated field identify discuss points consensus controversies astrocytes, starting their name. We then present emerging knowledge cells future challenges field.

Language: Английский

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A MnO₂ Nanoparticle-Dotted Hydrogel Promotes Spinal Cord Repair via Regulating Reactive Oxygen Species Microenvironment and Synergizing with Mesenchymal Stem Cells

ACS Nano, Journal Year: 2019, Volume and Issue: 13(12), P. 14283 - 14293

Published: Nov. 26, 2019

Spinal cord injury (SCI) is one of the most debilitating injuries, and transplantation stem cells in a scaffold promising strategy for treatment. However, cell treatment SCI has been severely impaired by increased generation reactive oxygen species lesion microenvironment, which can lead to high level death dysfunction. Herein, MnO2 nanoparticle (NP)-dotted hydrogel prepared through dispersion NPs PPFLMLLKGSTR peptide modified hyaluronic acid hydrogel. The peptide-modified enables adhesive growth mesenchymal (MSCs) nerve tissue bridging. alleviate oxidative environment, thereby effectively improving viability MSCs. Transplantation MSCs multifunctional gel generates significant motor function restoration on long-span rat spinal transection model induces an vivo integration as well neural differentiation implanted MSCs, leading highly efficient regeneration central nervous tissue. Therefore, NP-dotted represents stem-cell-based therapies system diseases comprehensive regulation pathological microenvironment complications.

Language: Английский

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Transplanting neural progenitor cells to restore connectivity after spinal cord injury

Nature reviews. Neuroscience, Journal Year: 2020, Volume and Issue: 21(7), P. 366 - 383

Published: June 9, 2020

Language: Английский

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Astrocytes in human central nervous system diseases: a frontier for new therapies

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

Published: Oct. 13, 2023

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence the central nervous system (CNS). contribute pathophysiology all neurological neuropsychiatric disorders in ways that can be either beneficial or detrimental disorder outcome. Pathophysiological changes astroglia primary secondary result gain loss functions. respond external, non-cell autonomous signals associated with any form CNS pathology by undergoing complex variable their structure, molecular expression, function. In addition, internally driven, cell astroglial innate properties lead pathologies. Astroglial is complex, different pathophysiological states phenotypes context-specific vary disorder, disorder-stage, comorbidities, age, sex. Here, we classify into (i) reactive astrogliosis, (ii) atrophy function, (iii) degeneration death, (iv) astrocytopathies characterised aberrant forms drive disease. We review across spectrum human diseases disorders, including neurotrauma, stroke, neuroinfection, autoimmune attack epilepsy, as well neurodevelopmental, neurodegenerative, metabolic disorders. Characterising cellular mechanisms represents new frontier identify novel therapeutic strategies.

Language: Английский

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