Evidence map›Paper›PMID 41852809›Full record

ArticleResearch (Washington, D.C.)2026

TRIM21 Exacerbates Ischemic Brain Injury by Promoting Astrocyte-Mediated Neuroinflammation via K63-Linked Ubiquitination of MDA5.

Yirui Kuang, Huaping Huang, Kaibo Yu, Tianchi Tang, Yonghe Zheng, Xian Yu, Linfeng Fan, Hang Zhou, Yin Li, Yinghan Guo and 9 more

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In one paragraph

Article in Research (Washington, D.C.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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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

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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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

19 authors.

Yirui KuangDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Huaping HuangDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Kaibo YuDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Tianchi TangDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Yonghe ZhengDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Xian YuDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Linfeng FanDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Hang ZhouDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Yin LiDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Yinghan GuoDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Yi ZhangState Key Laboratory of Transvascular Implantation Devices, Hangzhou, China.
Fengqi ZhouDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Jianru LiDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Chi GuDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Junyou WangDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Liya LinState Key Laboratory of Transvascular Implantation Devices, Hangzhou, China.
Guannan GuanDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Feng YanDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Gao ChenDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.ORCID https://orcid.org/0000-0003-1085-0028

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The pathophysiology of ischemic stroke is critically mediated by detrimental neuroinflammation. Tripartite motif-containing 21 (TRIM21) serves as an E3 ubiquitin ligase that regulates important biological functions. Nonetheless, the specific role of TRIM21 in neuroinflammation and ischemic brain injury remains unclear. In this study, we found that TRIM21 expression was up-regulated in astrocytes within the peri-infarct regions of mice subjected to transient middle cerebral artery occlusion (tMCAO) and in an in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) model. TRIM21 deficiency alleviated cerebral ischemia/reperfusion (I/R) injury by attenuating the inflammatory responses and oxidative stress. Mechanistically, our findings demonstrated that TRIM21 interacts with MDA5 and sequentially promotes the K63-linked ubiquitination and stabilization of MDA5, ultimately activating the nuclear factor κB (NF-κB) pathway in astrocytes. Moreover, MDA5 overexpression effectively reversed protective effects of TRIM21 deficiency after cerebral ischemia. Consistently, brain-targeted TRIM21 silencing with nanoparticle delivery considerably ameliorated cerebral I/R injury. Collectively, our findings identify TRIM21 as a novel astrocyte-specific mediator of neuroinflammation in cerebral ischemic injury and highlight its potential as a therapeutic target for ischemic stroke.

Identifiers

PMID41852809
PMCPMC12992933

What Socratic holds

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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 Socratic graph.