ArticleJournal of neuroinflammation2023
Sexually dimorphic extracellular vesicle responses after chronic spinal cord injury are associated with neuroinflammation and neurodegeneration in the aged brain.
Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Multiorgan transcriptomics and circulating extracellular vesicle profiling reveal age-dependent systemic vulnerability to isoflurane anesthesia and surgery.GeroScience · 2026Article
- Inflachromene Blocks Neuronal HMGB1 Translocation to Mitigate Hippocampal TLR4-NF-κB-Mediated Neuroinflammation and Depression-Like Behavior After Spinal Cord Injury.Molecular neurobiology · 2026Article
- Wnt5a-Induced Exosomes From Bone Marrow Mesenchymal Stem Cells Promote Spinal Cord Injury Repair by Modulating Immune Cell Phenotypes and Alleviating Neuroinflammation via the NF-κB Pathway.CNS neuroscience & therapeutics · 2026Article
- Systemic delivery of drug-free polymeric nanoparticles reprograms innate immunity in a sex-dependent manner after spinal cord injury.bioRxiv : the preprint server for biology · 2026Article
- Extracellular vesicle-based therapeutic strategies for spinal cord injury.Extracellular vesicles and circulating nucleic acids · 2026Review
- Unveiling the Proteomic Landscape of Extracellular Vesicles: Implications for Neurodegeneration and Neuroprotection.Journal of neurochemistry · 2026Review
- Small Extracellular Vesicles in Neurodegenerative Disease: Emerging Roles in Pathogenesis, Biomarker Discovery, and Therapy.International journal of molecular sciences · 2025Review
- Article
- Age-dependent Transcriptional and Circuit Alterations in the brain Underlie Post-Anesthesia Neurobehavioral Dysfunction.Aging and disease · 2025Article
- The potential mechanisms and regulatory roles of exosomal miRNA in neural repair after spinal cord injury.Frontiers in cellular neuroscience · 2025Review
- Sex as a biological variable in ageing: insights and perspectives on the molecular and cellular hallmarks.Open biology · 2024Review
- Old age alters inflammation and autophagy signaling in the brain, leading to exacerbated neurological outcomes after spinal cord injury in male mice.Brain, behavior, and immunity · 2024Article
- Spinal cord injury disrupts plasma extracellular vesicles cargoes leading to neuroinflammation in the brain and neurological dysfunction in aged male mice.Brain, behavior, and immunity · 2024Article
- Caffeic acid phenethyl ester inhibits neuro-inflammation and oxidative stress following spinal cord injury by mitigating mitochondrial dysfunction via the SIRT1/PGC1α/DRP1 signaling pathway.Journal of translational medicine · 2024Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMedical advances have made it increasingly possible for spinal cord injury (SCI) survivors to survive decades after the insult. But how SCI affects aging changes and aging impacts the injury process have received limited attention. Extracellular vesicles (EVs) are recognized as critical mediators of neuroinflammation after CNS injury, including at a distance from the lesion site. We have previously shown that SCI in young male mice leads to robust changes in plasma EV count and microRNA (miR) content. Here, our goal was to investigate the impact of biological sex and aging on EVs and brain after SCI.
methodsYoung adult age-matched male and female C57BL/6 mice were subjected to SCI. At 19 months post-injury, total plasma EVs were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis (NTA). EVs miR cargo was examined using the Fireplex® assay. The transcriptional changes in the brain were assessed by a NanoString nCounter Neuropathology panel and validated by Western blot (WB) and flow cytometry (FC). A battery of behavioral tests was performed for assessment of neurological function.
resultsTranscriptomic changes showed a high number of changes between sham and those with SCI. Sex-specific changes were found in transcription networks related to disease association, activated microglia, and vesicle trafficking. FC showed higher microglia and myeloid counts in the injured tissue of SCI/Female compared to their male counterparts, along with higher microglial production of ROS in both injured site and the brain. In the latter, increased levels of TNF and mitochondrial membrane potential were seen in microglia from SCI/Female. WB and NTA revealed that EV markers are elevated in the plasma of SCI/Male. Particle concentration in the cortex increased after injury, with SCI/Female showing higher counts than SCI/Male. EVs cargo analysis revealed changes in miR content related to injury and sex. Behavioral testing confirmed impairment of cognition and depression at chronic time points after SCI in both sexes, without significant differences between males and females.
conclusionsOur study is the first to show sexually dimorphic changes in brain after very long-term SCI and supports a potential sex-dependent EV-mediated mechanism that contributes to SCI-induced brain changes.
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