bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.05.13.653696

Differential effects of ischemia and inflammation on plasma-derived extracellular vesicle characteristics and function

Couch, Y.
View original source ↗Export metadata ↓

Abstract

Extracellular vesicles (EVs) have long been understood to be important mediators of cell-to-cell communication and may lead to the molecular aftermath and exacerbation of brain injuries such stroke. This study explored how the source of the EVs influenced their characteristics and the effect these differences had on naive brain tissue. EVs were isolated from animals post-stroke in the acute or chronic stages of recovery in animals with and without reperfusion, and from a model of systemic inflammation (i.p. lipopolysaccharide). The data show that neither stroke nor inflammation significantly increase EV numbers compared to sham or naive animals. Post-stroke EVs exhibited a panel of different platelet and inflammatory markers, when compared to EVs derived from a model of inflammation, reflecting differences between stroke and systemic immune activation. When injected into the brain, both stroke-derived and inflammation-derived EVs induced expression of pro-inflammatory cytokine gene expression, suggesting a potential role in neuroinflammation. However, there was a lack of distinct glial and astrocyte reactivity in response to any EVs, despite robust changes in ICAM reactivity. The findings here underscore the complexity of EV roles in pathophysiology and highlight the need for improved EV isolation methods. With further longitudinal studies we may be able to more accurately determine how the context of the injury (reperfusion vs no reperfusion vs inflammation) might contribute to the EV populations and their function. Understanding more about EVs in different contexts will improve our ability to use EVs as biomarkers, but also our capacity to interfere with EV biology as a novel therapeutic approach.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Couch, Y.. 2025-05-16. Differential effects of ischemia and inflammation on plasma-derived extracellular vesicle characteristics and function. https://doi.org/10.1101/2025.05.13.653696

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Functional validation of allele-specific LMNB1 silencing in patient-derived astrocytes as a therapeutic option for Autosomal Dominant Leukodystrophy

Adult-onset Autosomal Dominant Leukodystrophy (ADLD) is a rare fatal leukodystrophy caused by increased LMNB1 gene dosage, most commonly resulting from duplication of the LMNB1 locus. Because ADLD is a gene dosage disorder, selective reduction of pathological LMNB1 expression represents a rational therapeutic strategy. Although allele-specific RNA interference has previously been shown to lower LMNB1 levels in patient-derived fibroblasts and directly reprogrammed neurons, its therapeutic effects have not been evaluated in disease-relevant human glial cells or using functional efficacy endpoints. Here, we established human induced pluripotent stem cell-derived astrocytes from ADLD patients as a human glial model in which to validate allele-specific LMNB1 silencing across molecular, cellular, and functional readouts. ADLD astrocytes recapitulated increased LMNB1 expression and characteristic nuclear abnormalities and displayed transcriptional alterations affecting extracellular matrix organization, calcium homeostasis, metabolism and RNA processing. Functionally, these cells also exhibited functional phenotypes suitable for therapeutic evaluation: astrocyte-conditioned medium impaired the viability of both murine and human oligodendroglial cultures, while conditioned-medium and direct astrocyte-seeding paradigms revealed impaired post-lesion myelin recovery in lysolecithin-treated cerebellar organotypic slices. Allele-specific LMNB1 silencing restored physiological LMNB1 levels, corrected nuclear abnormalities, attenuated astrocyte-mediated oligodendroglial toxicity, improved post-lesion myelin recovery, and was associated with selective transcriptional programs associated with extracellular support and cholesterol metabolism. Together, these findings provide molecular, cellular, and functional validation of allele-specific LMNB1 dosage correction in patient-derived human astrocytes and offer key support for LMNB1-lowering strategies in disease-relevant human glial cells.

neuroscience↗
bioRxiv2026

Perceptual integration of multisensory haptic, visual, and auditory feedback for roughness discrimination in augmented reality

Understanding how our different senses interact to shape our perception is essential to design realistic and immersive virtual and augmented reality (VR/AR) experiences. The present study investigated how roughness perception can be modulated through haptic, visual, and auditory cues in AR using a vibrotactile wristband. Participants compared virtual textures varying in vibration frequency/amplitude, visual grain size, and friction sound. Results revealed strong linear relationships between stimulus parameters and perceived roughness, with haptic frequency and visual cues driving the highest discrimination performance. Adding non-informative sensory feedback reduced perceptual sensitivity, acting as noise. Individual differences emerged: participants who rated haptic as the easiest modality showed greater sensitivity to haptic variations, while visual-reliant participants performed better with visual cues. We conclude that roughness in AR can be systematically manipulated, but is vulnerable to perceptual interference from irrelevant inputs, where our work provides actionable insights for implementing optimized and adaptive AR/VR interfaces.

neuroscience↗
bioRxiv2026

Structural and functional MRI signatures of Gambling Disorder: a case-control study

Gambling disorder (GD) is a behavioural addiction that may help identify addiction-related neural features without the direct neurobiological effects of a primary substance of dependence. We examined regional grey matter volume (GMV) and resting-state functional connectivity (rsFC) in the same well-characterised sample. Eighteen men with GD and 21 matched healthy controls underwent high-resolution structural and resting-state functional MRI. GMV was quantified across 214 cortical and subcortical regions, and seed-based rsFC analyses focused on striatal subdivisions and mesocorticolimbic regions. Group differences were evaluated using permutation testing and cluster-corrected mixed-effects modelling. GD was associated with lower GMV in the ventromedial prefrontal cortex, orbitofrontal regions and other cortical and subcortical areas, alongside higher GMV in a subset of limbic and default-mode regions. Participants with GD also showed lower connectivity between the limbic striatum and the hippocampus, thalamus and putamen. In exploratory analyses, somatomotor connectivity was positively associated with gambling severity (Problem Gambling Severity Index: Spearman's rho = 0.71, p = 0.003, false-discovery-rate-adjusted q = 0.016). Structural and functional findings overlapped spatially in regions associated with valuation, memory, reward and habit formation, but regional GMV did not mediate group differences in rsFC. These findings are broadly consistent with corticostriatal models of GD and identify candidate circuit-level differences for independent replication. Larger, more diverse and longitudinal samples are required to establish their reproducibility, temporal direction and clinical relevance.

neuroscience↗