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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Molecular and spatial signatures of mouse brain aging at single-cell resolution

Cell, Journal Year: 2022, Volume and Issue: 186(1), P. 194 - 208.e18

Published: Dec. 28, 2022

The diversity and complex organization of cells in the brain have hindered systematic characterization age-related changes its cellular molecular architecture, limiting our ability to understand mechanisms underlying functional decline during aging. Here, we generated a high-resolution cell atlas aging within frontal cortex striatum using spatially resolved single-cell transcriptomics quantified gene expression spatial major types these regions over mouse lifespan. We observed substantially more pronounced state, expression, non-neuronal neurons. Our data revealed signatures glial immune activation aging, particularly enriched subcortical white matter, identified both similarities notable differences cell-activation patterns induced by systemic inflammatory challenge. These results provide critical insights into inflammation brain.

Language: Английский

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Beyond the GFAP-Astrocyte Protein Markers in the Brain

Biomolecules, Journal Year: 2021, Volume and Issue: 11(9), P. 1361 - 1361

Published: Sept. 14, 2021

The idea of central nervous system as one-man band favoring neurons is long gone. Now we all are aware that and neuroglia team players constant communication between those various cell types essential to maintain functional efficiency a quick response danger. Here, summarize discuss known new markers astroglial multiple functions, their natural heterogeneity, cellular interactions, aging disease-induced dysfunctions. This review focused on newly reported facts regarding astrocytes, which beyond the old stereotypes. We present an up-to-date list marker proteins used identify broad spectrum phenotypes related physiological pathological conditions. aim this help choose well-tailored for specific needs further experimental studies, precisely recognizing differential glial phenotypes, or diagnostic purposes. hope it will categorize structural diversity population ease clear readout future results.

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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Stroke subtype-dependent synapse elimination by reactive gliosis in mice

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Nov. 26, 2021

Abstract The pathological role of reactive gliosis in CNS repair remains controversial. In this study, using murine ischemic and hemorrhagic stroke models, we demonstrated that microglia/macrophages astrocytes are differentially involved engulfing synapses the region. By specifically deleting MEGF10 MERTK phagocytic receptors, determined inhibiting phagocytosis or improved neurobehavioral outcomes attenuated brain damage. stroke, but not outcomes. Single-cell RNA sequencing revealed related biological processes pathways were downregulated compared to brain. Together, these findings suggest microgliosis astrogliosis play individual roles mediating synapse engulfment pathologically distinct models preventing process could rescue loss.

Language: Английский

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Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(3), P. 445 - 465

Published: March 23, 2023

Language: Английский

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APOE mediated neuroinflammation and neurodegeneration in Alzheimer’s disease

Seminars in Immunology, Journal Year: 2022, Volume and Issue: 59, P. 101594 - 101594

Published: Jan. 1, 2022

Neuroinflammation is a central mechanism involved in neurodegeneration as observed Alzheimer's disease (AD), the most prevalent form of neurodegenerative disease. Apolipoprotein E4 (APOE4), strongest genetic risk factor for AD, directly influences onset and progression by interacting with major pathological hallmarks AD including amyloid-β plaques, neurofibrillary tau tangles, well neuroinflammation. Microglia astrocytes, two immune cells brain, exist an immune-vigilant state providing immunological defense housekeeping functions that promote neuronal well-being. It becoming increasingly evident under conditions, these become progressively dysfunctional regulating metabolic immunoregulatory pathways, thereby promoting chronic inflammation-induced neurodegeneration. Here, we review discuss how APOE specifically APOE4 pathology, disrupts microglial astroglial immunomodulating leading to inflammation contributes AD.

Language: Английский

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Reactive astrocytes facilitate vascular repair and remodeling after stroke

Cell Reports, Journal Year: 2021, Volume and Issue: 35(4), P. 109048 - 109048

Published: April 1, 2021

Brain injury causes astrocytes to assume a reactive state that is essential for early tissue protection, but how affect later reparative processes incompletely understood. In this study, we show are crucial vascular repair and remodeling after ischemic stroke in mice. Analysis of astrocytic gene expression data reveals substantial activation transcriptional programs related stroke. vivo two-photon imaging provides evidence contacting newly formed vessels cortex surrounding photothrombotic infarcts. Chemogenetic ablation subset dramatically impairs extracellular matrix remodeling. This disruption accompanied by prolonged blood flow deficits, exacerbated permeability, ongoing cell death, worsened motor recovery. contrast, structure the non-ischemic brain unaffected focal astrocyte ablation. These findings position as critical cellular mediators functionally important during neural repair.

Language: Английский

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Divergent transcriptional regulation of astrocyte reactivity across disorders

Nature, Journal Year: 2022, Volume and Issue: 606(7914), P. 557 - 564

Published: May 25, 2022

Language: Английский

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Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease

Nature Neuroscience, Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 2, 2023

Language: Английский

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