Brain-Derived Extracellular Vesicles in Health and Disease: A Methodological Perspective

Brenna, Santra; Altmeppen, Hermann; Magnus, Tim; Puig, Berta

doi:10.3390/ijms22031365

Cited by 24 publications

(17 citation statements)

References 113 publications

(165 reference statements)

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“…Most studies have isolated the neuron-derived EVs directly from brain tissue [17]. Taking into account the translational nature of the present study, we decided to use a less invasive method for isolating circulating neuron-derived EVs from the serum.…”

Section: Proteomic Analysis Of Neuron-derived Extracellular Vesiclesmentioning

confidence: 99%

Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke

et al. 2021

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In order to investigate the role of circulating extracellular vesicles (EVs), proteins, and microRNAs as damage and repair markers in ischaemic stroke depending on its topography, subcortical (SC), and cortical-subcortical (CSC) involvement, we quantified the total amount of EVs using an enzyme-linked immunosorbent assay technique and analysed their global protein content using proteomics. We also employed a polymerase chain reaction to evaluate the circulating microRNA profile. The study included 81 patients with ischaemic stroke (26 SC and 55 CSC) and 22 healthy controls (HCs). No differences were found in circulating EV levels between the SC, CSC, and HC groups. We detected the specific expression of C1QA and Casp14 in the EVs of patients with CSC ischaemic stroke and the specific expression of ANXA2 in the EVs of patients with SC involvement. Patients with CSC ischaemic stroke showed a lower expression of miR-15a, miR-424, miR-100, and miR-339 compared with those with SC ischaemic stroke, and the levels of miR-339, miR-100, miR-199a, miR-369a, miR-424, and miR-15a were lower than those of the HCs. Circulating EV proteins and microRNAs from patients with CSC ischaemic stroke could be considered markers of neurite outgrowth, neurogenesis, inflammation process, and atherosclerosis. On the other hand, EV proteins and microRNAs from patients with SC ischaemic stroke might be markers of an anti-inflammatory process and blood–brain barrier disruption reduction.

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Section: Proteomic Analysis Of Neuron-derived Extracellular Vesiclesmentioning

confidence: 99%

Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke

et al. 2021

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“…Although the type of sample and the isolation methods impact the RNA yield and size distribution [ 55 ], and though the protocols differ between that and our study, the finding could indicate a general lack (or at least relatively reduced presence) of mRNA in larger EVs. Notably, in our previous study [ 32 ] we showed that sBDEVs were enriched in ribosomal proteins when compared to BDEVs that were not filtered and, in fact, ribosomal proteins are commonly found in BDEVs even when using different isolation protocols [ 56 ]. Even though it has been shown that EVs do not have the appropriate machinery to translate mRNA directly within the vesicles (at least in cultured cell lines [ 10 ]), it could be hypothesized that they could deliver most of the translation machinery plus the mRNA onto recipient cells, particularly as tRNA have also been found in BDEVs [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Multiplexed mRNA analysis of brain-derived extracellular vesicles upon experimental stroke in mice reveals increased mRNA content with potential relevance to inflammation and recovery processes

Bub

Brenna

Alawi

et al. 2022

Cell. Mol. Life Sci.

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Extracellular vesicles (EVs) are lipid bilayer-enclosed structures that represent newly discovered means for cell-to-cell communication as well as promising disease biomarkers and therapeutic tools. Apart from proteins, lipids, and metabolites, EVs can deliver genetic information such as mRNA, eliciting a response in the recipient cells. In the present study, we have analyzed the mRNA content of brain-derived EVs (BDEVs) isolated 72 h after experimental stroke in mice and compared them to controls (shams) using nCounter® Nanostring panels, with or without prior RNA isolation. We found that both panels show similar results when comparing upregulated mRNAs in stroke. Notably, the highest upregulated mRNAs were related to processes of stress and immune system responses, but also to anatomical structure development, cell differentiation, and extracellular matrix organization, thus indicating that regenerative mechanisms already take place at this time-point. The five top overrepresented mRNAs in stroke mice were confirmed by RT-qPCR and, interestingly, found to be full-length. We could reveal that the majority of the mRNA cargo in BDEVs was of microglial origin and predominantly present in small BDEVs (≤ 200 nm in diameter). However, the EV population with the highest increase in the total BDEVs pool at 72 h after stroke was of oligodendrocytic origin. Our study shows that nCounter® panels are a good tool to study mRNA content in tissue-derived EVs as they can be carried out even without previous mRNA isolation, and that the mRNA cargo of BDEVs indicates a possible participation in inflammatory but also recovery processes after stroke.

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“…EVs are important mediators of communication between cells, and it has been identified that native brain cell-released EVs present tropism to injured regions [ 52 , 53 , 54 ]. Additionally, it has already been shown that intranasally administrated MSC-derived EVs were identified in brain cells [ 41 , 42 ], presenting tropism to injured brain regions [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Functional Recovery Caused by Human Adipose Tissue Mesenchymal Stem Cell-Derived Extracellular Vesicles Administered 24 h after Stroke in Rats

Rohden

Teixeira

Bernardi

et al. 2021

IJMS

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Ischemic stroke is a major cause of death and disability, intensely demanding innovative and accessible therapeutic strategies. Approaches presenting a prolonged period for therapeutic intervention and new treatment administration routes are promising tools for stroke treatment. Here, we evaluated the potential neuroprotective properties of nasally administered human adipose tissue mesenchymal stem cell (hAT-MSC)-derived extracellular vesicles (EVs) obtained from healthy individuals who underwent liposuction. After a single intranasal EV (200 µg/kg) administered 24 h after a focal permanent ischemic stroke in rats, a higher number of EVs, improvement of the blood–brain barrier, and re-stabilization of vascularization were observed in the recoverable peri-infarct zone, as well as a significant decrease in infarct volume. In addition, EV treatment recovered long-term motor (front paws symmetry) and behavioral impairment (short- and long-term memory and anxiety-like behavior) induced by ischemic stroke. In line with these findings, our work highlights hAT-MSC-derived EVs as a promising therapeutic strategy for stroke.

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Brain-Derived Extracellular Vesicles in Health and Disease: A Methodological Perspective

Cited by 24 publications

References 113 publications

Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke

Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke

Multiplexed mRNA analysis of brain-derived extracellular vesicles upon experimental stroke in mice reveals increased mRNA content with potential relevance to inflammation and recovery processes

Functional Recovery Caused by Human Adipose Tissue Mesenchymal Stem Cell-Derived Extracellular Vesicles Administered 24 h after Stroke in Rats

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