Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury

Cells, Год журнала: 2024, Номер 13(2), С. 148 - 148

Опубликована: Янв. 12, 2024

Traumatic Brain Injury (TBI) represents a significant health concern, necessitating advanced therapeutic interventions. This detailed review explores the critical roles of astrocytes, key cellular constituents central nervous system (CNS), in both pathophysiology and possible rehabilitation TBI. Following injury, astrocytes exhibit reactive transformations, differentiating into pro-inflammatory (A1) neuroprotective (A2) phenotypes. paper elucidates interactions with neurons, their role neuroinflammation, potential for exploitation. Emphasized strategies encompass utilization endocannabinoid calcium signaling pathways, hormone-based treatments like 17β-estradiol, biological therapies employing anti-HBGB1 monoclonal antibodies, gene therapy targeting Connexin 43, innovative technique astrocyte transplantation as means to repair damaged neural tissues.

Язык: Английский

---

Synergistic effects of tetramethylpyrazine and astragaloside IV on spinal cord injury via alteration of astrocyte A1/A2 polarization through the Sirt1-NF-κB pathway

International Immunopharmacology, Год журнала: 2024, Номер 131, С. 111686 - 111686

Опубликована: Март 10, 2024

Язык: Английский

---

Stem Cell-Derived Extracellular Vesicle-Mediated Therapeutic Signaling in Spinal Cord Injury

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 723 - 723

Опубликована: Янв. 16, 2025

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising therapeutic strategy for spinal cord injury (SCI). These nanosized possess unique properties such low immunogenicity and the ability to cross biological barriers, making them ideal carriers delivering bioactive molecules injured tissues. MSC-EVs been demonstrated exert multiple beneficial effects in SCI, including reducing inflammation, promoting neuroprotection, enhancing axonal regeneration. Recent studies delved into molecular mechanisms underlying MSC-EV-mediated effects. Exosomal microRNAs (miRNAs) identified key regulators of various cellular processes involved SCI pathogenesis repair. miRNAs can influence oxidative stress, apoptosis by modulating gene expression. This review summarized current state MSC-EV-based therapies highlighting potential clinical applications. We discussed challenges limitations translating these practice, inconsistent EV production, complex cargo composition, need targeted delivery strategies. Future research should focus on optimizing production characterization, identifying miRNAs, developing innovative systems maximize SCI.

Язык: Английский

---

Chronic spinal cord injury repair by NT3-chitosan only occurs after clearance of the lesion scar

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июнь 17, 2022

Abstract Spinal cord injury (SCI) is a severe damage usually leading to limb dysesthesia, motor dysfunction, and other physiological disability. We have previously shown that NT3-chitosan could trigger an acute SCI repairment in rats non-human primates. Due the negative effect of inhibitory molecules glial scar on axonal regeneration, however, role treatment chronic remains unclear. Compared with fresh wound SCI, how handle lesion core scars major issue related chronic-SCI repair. Here we report, complete rat model, establishment magnetic resonance-diffusion tensor imaging (MR-DTI) methods monitor spatial temporal changes area, which matched well anatomical analyses. Clearance via suction cystic tissues trimming solid before introducing using either rigid tubular scaffold or soft gel form led robust neural interconnected severed ascending descending axons accompanied electrophysiological functional recovery. In contrast, tissue extraction without followed by injection, resulted little, if any regeneration. Taken together, after clearance, can be used enable repair MR-DTI-based mapping area monitoring ongoing regeneration potentially implemented clinical studies for subacute/chronic-SCI

Язык: Английский

---

Tackling the glial scar in spinal cord regeneration: new discoveries and future directions

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Май 24, 2023

Axonal regeneration and functional recovery are poor after spinal cord injury (SCI), typified by the formation of an scar. While this scar was traditionally believed to be primarily responsible for axonal failure, current knowledge takes a more holistic approach that considers intrinsic growth capacity axons. Targeting SCI has also not reproducibly yielded nearly same efficacy in animal models compared these neuron-directed approaches. These results suggest major reason behind central nervous system (CNS) failure is but stimulate axon adequately. findings raise questions about whether targeting neuroinflammation glial scarring still constitute viable translational avenues. We provide comprehensive review dual role how future research can produce therapeutic strategies hurdles posed processes without compromising neuroprotection.

Язык: Английский

---

Multipotent Mesenchymal Stem Cell-Based Therapies for Spinal Cord Injury: Current Progress and Future Prospects

Biology, Год журнала: 2023, Номер 12(5), С. 653 - 653

Опубликована: Апрель 26, 2023

Spinal cord injury (SCI) represents a significant medical challenge, often resulting in permanent disability and severely impacting the quality of life for affected individuals. Traditional treatment options remain limited, underscoring need novel therapeutic approaches. In recent years, multipotent mesenchymal stem cells (MSCs) have emerged as promising candidate SCI due to their multifaceted regenerative capabilities. This comprehensive review synthesizes current understanding molecular mechanisms underlying MSC-mediated tissue repair SCI. Key discussed include neuroprotection through secretion growth factors cytokines, promotion neuronal regeneration via MSC differentiation into neural cell types, angiogenesis release pro-angiogenic factors, immunomodulation by modulating immune activity, axonal driven neurotrophic glial scar reduction modulation extracellular matrix components. Additionally, examines various clinical applications MSCs treatment, such direct transplantation injured spinal cord, engineering using biomaterial scaffolds that support survival integration, innovative cell-based therapies like MSC-derived exosomes, which possess neuroprotective properties. As field progresses, it is crucial address challenges associated with MSC-based therapies, including determining optimal sources, intervention timing, delivery methods, well developing standardized protocols isolation, expansion, characterization. Overcoming these will facilitate translation preclinical findings practice, providing new hope improved individuals living devastating consequences

Язык: Английский

---

Small leucine-rich proteoglycans inhibit CNS regeneration by modifying the structural and mechanical properties of the lesion environment

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Окт. 26, 2023

Extracellular matrix (ECM) deposition after central nervous system (CNS) injury leads to inhibitory scarring in humans and other mammals, whereas it facilitates axon regeneration the zebrafish. However, molecular basis of these different fates is not understood. Here, we identify small leucine-rich proteoglycans (SLRPs) as a contributing factor failure mammals. We demonstrate that SLRPs chondroadherin, fibromodulin, lumican, prolargin are enriched rodent human but zebrafish CNS lesions. Targeting ECM inhibits functional recovery. Mechanistically, find confer mechano-structural properties lesion environment adverse growth. Our study reveals factors impair by modifying tissue mechanics structure, identifies their enrichment feature brain spinal cord These findings imply may be targets for therapeutic strategies promote regeneration.

Язык: Английский

---

Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

Neural Regeneration Research, Год журнала: 2024, Номер 20(4), С. 973 - 989

Опубликована: Май 16, 2024

Traumatic brain injury is a global health crisis, causing significant death and disability worldwide. Neuroinflammation that follows traumatic has serious consequences for neuronal survival cognitive impairments, with astrocytes involved in this response. Following injury, rapidly become reactive, astrogliosis propagates from the core to distant regions. Homeostatic astroglial proteins are downregulated near core, while pro-inflammatory genes overexpressed. This altered gene expression considered pathological remodeling of produces recovery. In addition, glial scar formed by reactive initially necessary limit immune cell infiltration, but long term impedes axonal reconnection functional Current therapeutic strategies focused on preventing acute complications. Statins, cannabinoids, progesterone, beta-blockers, cerebrolysin demonstrate neuroprotective benefits most them have not been studied context astrocytes. review, we discuss signaling pathways activated following some potential new aimed modulate responses especially using cell-targeted miRNAs or lncRNA, viral vectors, repurposed drugs.

Язык: Английский

---

Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 15, 2024

Adult zebrafish have an innate ability to recover from severe spinal cord injury. Here, we report a comprehensive single nuclear RNA sequencing atlas that spans 6 weeks of regeneration. We identify cooperative roles for adult neurogenesis and neuronal plasticity during repair. Neurogenesis glutamatergic GABAergic neurons restores the excitatory/inhibitory balance after In addition, transient population injury-responsive (iNeurons) show elevated 1 week post-injury. found iNeurons are injury-surviving acquire neuroblast-like gene expression signature CRISPR/Cas9 mutagenesis showed required functional recovery employ vesicular trafficking as essential mechanism underlies plasticity. This study provides resource cells mechanisms direct regeneration establishes model plasticity-driven neural

Язык: Английский

---

Spatiotemporal transcriptomic map of glial cell response in a mouse model of acute brain ischemia

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(46)

Опубликована: Ноя. 5, 2024

The role of nonneuronal cells in the resolution cerebral ischemia remains to be fully understood. To decode key molecular and cellular processes that occur after ischemia, we performed spatial single-cell transcriptomic profiling male mouse brain during first week injury. Cortical gene expression was severely disrupted, defined by inflammation cell death lesion core, glial scar formation orchestrated multiple types on periphery. identified as a zone with intense cell–cell communication, prominent ApoE-Trem2 signaling pathway modulating microglial activation. For each three major populations, an inflammatory-responsive state, resembling reactive states observed neurodegenerative contexts, observed. recovered spectrum ischemia-induced oligodendrocyte supports emerging hypothesis oligodendrocytes actively respond modulate neuroinflammatory stimulus. findings are further supported analysis other datasets from different models ischemic Collectively, present landmark dataset accompanied interactive visualization provides comprehensive view spatiotemporal organization postischemic brain.

Язык: Английский

---