Evidence map›Paper›PMID 37611902›Full record

ArticleAging and disease2024

M2 Microglial Extracellular Vesicles Attenuated Blood-brain Barrier Disruption via MiR-23a-5p in Cerebral Ischemic Mice.

Jia-Ji Pan, Lin Qi, Liping Wang, Chang Liu, Yaying Song, Muyassar Mamtilahun, Xiaowen Hu, Yongfang Li, Xiao Chen, Haroon Khan and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging and disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 31 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Jia-Ji PanDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Lin QiSchool of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Liping WangDepartment of Neurology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200120, China.
Chang LiuSchool of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Yaying SongDepartment of Neurology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200120, China.
Muyassar MamtilahunSchool of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Xiaowen HuSchool of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Yongfang LiDepartment of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Xiao ChenDepartment of Neurosurgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Haroon KhanSchool of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Qun XuHealth Management Center, Department of Neurology, Renji Hospital of Medical School of Shanghai Jiaotong University, Shanghai, 200127, China.
Yongting WangSchool of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Yaohui TangSchool of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Guo-Yuan YangSchool of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Zhijun ZhangSchool of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Shanghai Jiao Tong University · CNRenji Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Protecting the integrity of the blood-brain barrier (BBB) is crucial for maintaining brain homeostasis after ischemic stroke. Previous studies showed that M2 microglial extracellular vesicles (EVs) played a neuroprotective role in cerebral ischemia. However, the role of M2 microglial EVs in maintaining BBB integrity is unclear. Therefore, we explored the mechanisms of M2 microglial EVs in regulating BBB integrity. To identify microglial EVs, we used nanoparticle tracking analysis, transmission electron microscopy, and western blot analysis. Adult male ICR mice were subjected to 90-min middle cerebral artery occlusion (MCAO), followed by the injection of PKH26-labeled M2 microglial EVs via the tail vein. After MCAO, we assessed brain infarct and edema volume, as well as modified neurological severity score. BBB integrity was measured by assessing IgG leakage. The effects of M2 microglial EVs on astrocytes and endothelial cells were also examined. To investigate the molecular mechanisms, we performed RNA sequencing, miR-23a-5p knockdown, and luciferase reporter assays. Our results showed that PKH26-labeled microglial EVs were mainly taken up by neurons and glial cells. M2 microglial EVs treatment decreased brain infarct and edema volume, modified neurological severity score, and IgG leakage, while increasing the ZO-1, occludin, and claudin-5 expression after MCAO. Knockdown of miR-23a-5p reversed these effects. RNA sequencing revealed that the TNF, MMP3 and NFκB signaling pathway involved in regulating BBB integrity. Luciferase reporter assay showed that miR-23a-5p could bind to the 3' UTR of TNF. M2 microglial EVs-derived miR-23a-5p decreased TNF, MMP3 and NFκB p65 expression in astrocytes after oxygen-glucose deprivation, thereby increasing ZO-1 and Claudin-5 expression in bEnd.3 cells. In conclusion, our findings demonstrated that M2 microglial EVs attenuated BBB disruption after cerebral ischemia by delivering miR-23a-5p, which targeted TNF and regulated MMP3 and NFκB p65 expression.

Indexed as

Blood-Brain BarrierExtracellular VesiclesInfarction, Middle Cerebral ArteryMicrogliaMicroRNAsAnimalsAstrocytesClaudin-5Disease Models, AnimalMaleMatrix Metalloproteinase 3MiceMice, Inbred ICRTranscription Factor RelAZonula Occludens-1 ProteinClaudin-5Matrix Metalloproteinase 3MicroRNAsMirn23b microRNA, mouseTranscription Factor RelAZonula Occludens-1 Protein

Identifiers

PMID37611902
PMCPMC11081152
OpenAlexW4386117009

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.