The evolving role of extracellular vesicles (exosomes) as biomarkers in traumatic brain injury: Clinical perspectives and therapeutic implications

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: Oct. 6, 2022

Developing effective disease-modifying therapies for neurodegenerative diseases (NDs) requires reliable diagnostic, disease activity, and progression indicators. While desirable, identifying biomarkers NDs can be difficult because of the complex cytoarchitecture brain distinct cell subsets seen in different parts central nervous system (CNS). Extracellular vesicles (EVs) are heterogeneous, cell-derived, membrane-bound involved intercellular communication transport cell-specific cargos, such as proteins, Ribonucleic acid (RNA), lipids. The types EVs include exosomes, microvesicles, apoptotic bodies based on their size origin biogenesis. A growing body evidence suggests that mediated through is responsible disseminating important proteins implicated traumatic injury (TBI) other NDs. Some studies showed TBI a risk factor In terms therapeutic potential, outperform alternative synthetic drug delivery methods they transverse blood-brain barrier (BBB) without inducing immunogenicity, impacting neuroinflammation, immunological responses, prolonged bio-distribution. Furthermore, EV production varies across represents intracellular processes. Moreover, proteomic markers, which represent variety pathological processes, cellular damage or have been frequently studied neurotrauma research. However, blood-based short half-lives easily susceptible to degradation. EV-based may genetic neurometabolic abnormalities occur post-TBI. These not caught by proteomics, less degradation hence more reflective these modifications (cellular neuroinflammation). current narrative comprehensive review, we sought discuss contemporary knowledge better understanding research TBI, thus its applications modern medicine. utilization circulating diagnosis, developments therapies, managing associated challenges opportunities.

Language: Английский

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Extracellular vesicle-mediated bidirectional communication between heart and other organs

AJP Heart and Circulatory Physiology, Journal Year: 2022, Volume and Issue: 322(5), P. H769 - H784

Published: Feb. 18, 2022

In recent years, a wealth of studies has identified various molecular species released by cardiac muscle under physiological and pathological conditions that exert local paracrine and/or remote endocrine effects. Conversely, humoral factors, principally produced organs such as skeletal muscle, kidney, or adipose tissue, may affect the function metabolism normal diseased hearts. Although this cross communication within tissue between heart other is supported mounting evidence, research on role mediators carried exosomes, microvesicles, apoptotic bodies, collectively defined extracellular vesicles (EVs), at an early stage investigation. Once in circulation, EVs can potentially reach any organ where they transfer their cargo proteins, lipids, nucleic acids potent biological effects recipient cells. there are few cases signaling was clearly demonstrated, results from many only be tentatively inferred based indirect evidence obtained infusing exogenous experimental animals adding them to cell cultures. This area rapid expansion most mechanistic interpretations change near future; hence, present review played EV-carried two-way kidneys, bone marrow, lungs, liver, brain necessarily limited. Nonetheless, available data already unveiling new, intriguing, ample scenarios physiology pathophysiology.

Language: Английский

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Cell-Derived Exosomes as Therapeutic Strategies and Exosome-Derived microRNAs as Biomarkers for Traumatic Brain Injury

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(11), P. 3223 - 3223

Published: June 5, 2022

Traumatic brain injury (TBI) is a complex, life-threatening condition that causes mortality and disability worldwide. No effective treatment has been clinically verified to date. Achieving drug delivery across the blood-brain barrier (BBB) presents major challenge therapeutic development for TBI. Furthermore, field of TBI biomarkers rapidly developing cope with many aspects pathology enhance clinical management Exosomes (Exos) are endogenous extracellular vesicles (EVs) containing various biological materials, including lipids, proteins, microRNAs, other nucleic acids. Compelling evidence exists Exos, such as stem cell-derived Exos even neuron or glial promising strategies because they pass through BBB have potential deliver molecules target lesions. Meanwhile, decreased safety risks from intravenous injection orthotopic transplantation viable cells, microvascular occlusion imbalanced growth transplanted cells. These unique characteristics also create contents, especially Exos-derived appealing in In this review, we explore impact exosome-derived microRNAs on diagnosis, therapy, prognosis prediction The associated challenges opportunities discussed.

Language: Английский

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Bone marrow stromal cells-derived exosomes reduce neurological damage in traumatic brain injury through the miR-124-3p/p38 MAPK/GLT-1 axis

Experimental Neurology, Journal Year: 2023, Volume and Issue: 365, P. 114408 - 114408

Published: April 13, 2023

Mounting evidence indicates that stem cell-derived exosomal miRNAs have therapeutic effects on traumatic brain injury (TBI). This research is focused exploring the molecular processes of miR-124-3p obtained from bone marrow stromal cells-derived exosomes (BMSCs-Exos) in attenuating posttraumatic glutamate-mediated excitotoxicity.We created a TBI rat model and analyzed expression profile miRNA through microarray. The p38 MAPK levels were utilizing RT-qPCR western blotting. Dual-luciferase reporter (DLR) assay showed targeting relationship between MAPK. We subsequently conducted TUNEL flow cytometry to evaluate neuronal apoptotic rate an vitro excitotoxicity treated with BMSCs-Exos enriched (BMSCs-ExosmiR-124-3p). Moreover, glutamate transporter-1 (GLT-1) measured by Furthermore, BMSCs-ExosmiR-124-3p administered rats, their neuroprotective observed using blotting, immunohistochemistry, histological staining, magnetic resonance imaging (MRI), Morris water maze (MWM).The results revealed brains rats exhibited lowered enhanced levels. DLR demonstrated miR-124-3p's role negatively regulating its expression. In vivo studies confirmed attenuated downregulating upregulating GLT-1 expressions via transferring miR-124-3p. histopathological evaluation MRI remarkably alleviated cell death minimized lesion volumes post-TBI. MWM outcomes illustrated treatment could substantially improve neurological function inhibitor SB203580 similar BMSCs-ExosmiR-124-3p.Overall, current report highlighted can lead upregulation models inhibiting signaling pathway, hence alleviating damage

Language: Английский

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Engineered exosomes enriched with select microRNAs amplify their therapeutic efficacy for traumatic brain injury and stroke

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: March 19, 2024

Traumatic brain injury (TBI) and stroke stand as prominent causes of global disability mortality. Treatment strategies for TBI are shifting from targeting neuroprotection toward cell-based neurorestorative strategy, aiming to augment endogenous remodeling, which holds considerable promise the treatment stroke. Compelling evidence underscores that therapeutic effects therapy mediated by active generation release exosomes administered cells. Exosomes, endosomal derived nano-sized extracellular vesicles, play a pivotal role in intercellular communication. Thus, we may independently employ treat TBI. Systemic administration mesenchymal stem cell (MSC) promotes neuroplasticity neurological functional recovery preclinical animal models In this mini review, describe properties recent exosome-based therapies It is noteworthy microRNA cargo within contributes their effects. provide brief introduction microRNAs insight into key roles mediating With increasing knowledge exosomes, researchers have "engineered" exosome content amplify benefits. We therefore focus our discussion on benefits recently employed microRNA-enriched engineered exosomes. also discuss current opportunities challenges translating clinical applications.

Language: Английский

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Role of Exosomes in Brain Diseases

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Sept. 13, 2021

Exosomes are a subset of extracellular vesicles that act as messengers to facilitate communication between cells. Non-coding RNAs, proteins, lipids, and microRNAs delivered by the exosomes target molecules (such mRNAs, or DNA) host cells, thereby playing key role in maintenance normal brain function. However, also involved occurrence, prognosis, clinical treatment diseases, such Alzheimer's disease, Parkinson's stroke, traumatic injury. In this review, we have summarized novel findings elucidate diseases.

Language: Английский

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Neural Stem Cell Extracellular Vesicles Carrying YBX1 Inhibited Neuronal Pyroptosis Through Increasing m6A-modified GPR30 Stability and Expression in Ischemic Stroke

Translational Stroke Research, Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 15, 2023

Language: Английский

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Role of regulatory non-coding RNAs in traumatic brain injury

Neurochemistry International, Journal Year: 2023, Volume and Issue: 172, P. 105643 - 105643

Published: Nov. 24, 2023

Language: Английский

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Mesenchymal stem cell‐derived extracellular vesicles: Recent therapeutics and targeted drug delivery advances

Journal of Extracellular Biology, Journal Year: 2024, Volume and Issue: 3(5)

Published: May 1, 2024

Abstract The targeted drug delivery field is rapidly advancing, focusing on developing biocompatible nanoparticles that meet rigorous criteria of non‐toxicity, biocompatibility, and efficient release encapsulated molecules. Conventional synthetic (SNPs) face complications such as elevated immune responses, complex synthesis methods, toxicity, which restrict their utility in therapeutics delivery. Extracellular vesicles (EVs) have emerged promising substitutes for SNPs, leveraging ability to cross biological barriers, reduced natural origin. Notably, mesenchymal stem cell‐derived EVs (MSC‐EVs) garnered much curiosity due potential Studies suggest MSC‐EVs, the central paracrine contributors MSCs, replicate therapeutic effects MSCs. This review explores characteristics emphasizing various diseases, including CRISPR/Cas9 gene editing. It also delves into obstacles challenges MSC‐EVs clinical applications provides insights strategies overcome limitations biodistribution target

Language: Английский

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Exosomes as a therapeutic tool to promote neurorestoration and cognitive function in neurological conditions: Achieve two ends with a single effort

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(5)

Published: May 1, 2024

Abstract Exosomes possess a significant role in intercellular communications. In the nervous system, various neural cells release exosomes that not only own communications but also eliminate waste of cells, maintain myelin sheath, facilitate neurogenesis, and specifically assist normal cognitive function. neurological conditions including Parkinson's disease (PD), Alzheimer's (AD), traumatic brain injury (TBI), stroke, exosomal cargo like miRNAs take part sequela serve as diagnostic tool disorders, too. are their inhibition or administration from sources mesenchymal stem serum, which have shown worthy potential to treat multiple disorders. addition neurodegenerative manifestations, deficiencies an integral diseases, applying improving both aspects these diseases has been promising. This review discusses status exosome therapy neurorestorative function following disease.

Language: Английский

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