ArticleBrain, behavior, and immunity2023
Intranasally administered human MSC-derived extracellular vesicles inhibit NLRP3-p38/MAPK signaling after TBI and prevent chronic brain dysfunction.
Article in Brain, behavior, and immunity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Microglia in Post-Traumatic Brain Injury (TBI) Cognitive Impairment: From Pathological Changes to Therapeutic Approaches.CNS neuroscience & therapeutics · 2025Pooled it
- Ultrashort wave therapy promotes traumatic brain injury recovery by suppressing neuroinflammation.Neural regeneration research · 2026Article
- The Dual Roles of Extracellular Vesicle Subtypes in Regulating Traumatic Brain Injury.International journal of molecular sciences · 2026Review
- Article
- Role of miRNAs from mesenchymal stem cell-derived extracellular vesicles in neuroinflammation and behavioral impairments induced by chronic alcohol consumption in female mice.Neural regeneration research · 2026Article
- Effects of MMP8 inhibitors on chronic unpredictable mild stress-induced neuroinflammation and depressive-like behavior：exploring the underlying molecular mechanisms.Psychopharmacology · 2026Article
- Mesenchymal stem cells and secretome as modulators of neuroinflammation in neurological disorders.Journal of translational medicine · 2026Review
- The role of natural and engineered exosomes in repairing damage to the nervous system.Journal of nanobiotechnology · 2026Review
- Exploiting the role of milk extracellular vesicles: a comprehensive analysis on isolation methods, characterization, surface modifications, and their therapeutic applications.Journal of nanobiotechnology · 2026Review
- IL-18-Mediated Tumor Immune Evasion.Current issues in molecular biology · 2026Review
- An autonomous siRNA delivery system targeting NLRP3: implications in Parkinson's disease.BMC medicine · 2026Article
- Downregulation of neuronal DRD2 drives microglia synaptic pruning and results in cognitive deficits by promoting CCL2 release in a rat model of chronic migraine.The journal of headache and pain · 2026Article
- Intranasal Human NSC-Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS-STING Signalling, in Aged Hippocampus.Journal of extracellular vesicles · 2026Article
- Mesenchymal Stem Cell Therapy Modulates Peripheral-Central Immune Interactions and Attenuates Neuroinflammation-Driven Cognitive Dysfunction.International journal of molecular sciences · 2026Article
- Therapeutic potential of stem cell-derived extracellular vesicles in aging and regeneration.Frontiers in aging · 2026Review
- Cytokines and related signaling pathways in traumatic brain injury.Frontiers in immunology · 2026Review
- Investigating the Role of KNG1 in Traumatic Brain Injury.Journal of inflammation research · 2026Article
- Article
- Mesenchymal stromal cells and paracrine modulation of neuroplasticity in the central nervous system.EXCLI journal · 2026Review
- After Traumatic Brain Injury, EPHA4 Enhances Endoplasmic Reticulum Stress to Promote M1 Microglial Polarization Through the MAPK Signaling Pathway.Mediators of inflammation · 2026Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Traumatic brain injury (TBI) leads to lasting brain dysfunction with chronic neuroinflammation typified by nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome activation in microglia. This study probed whether a single intranasal (IN) administration of human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs) naturally enriched with activated microglia-modulating miRNAs can avert chronic adverse outcomes of TBI. Small RNA sequencing confirmed the enrichment of miRNAs capable of modulating activated microglia in hMSC-EV cargo. IN administration of hMSC-EVs into adult mice ninety minutes after the induction of a unilateral controlled cortical impact injury resulted in their incorporation into neurons and microglia in both injured and contralateral hemispheres. A single higher dose hMSC-EV treatment also inhibited NLRP3 inflammasome activation after TBI, evidenced by reduced NLRP3, apoptosis-associated speck-like protein containing a CARD, activated caspase-1, interleukin-1 beta, and IL-18 levels in the injured brain. Such inhibition in the acute phase of TBI endured in the chronic phase, which could also be gleaned from diminished NLRP3 inflammasome activation in microglia of TBI mice receiving hMSC-EVs. Proteomic analysis and validation revealed that higher dose hMSC-EV treatment thwarted the chronic activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway by IL-18, which decreased the release of proinflammatory cytokines. Inhibition of the chronic activation of NLRP3-p38/MAPK signaling after TBI also prevented long-term cognitive and mood impairments. Notably, the animals receiving higher doses of hMSC-EVs after TBI displayed better cognitive and mood function in all behavioral tests than animals receiving the vehicle after TBI. A lower dose of hMSC-EV treatment also partially improved cognitive and mood function. Thus, an optimal IN dose of hMSC-EVs naturally enriched with activated microglia-modulating miRNAs can inhibit the chronic activation of NLRP3-p38/MAPK signaling after TBI and prevent lasting brain dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.