Evidence map›Paper›PMID 33414375›Full record

ArticleCell death & disease2021

TRAF3 mediates neuronal apoptosis in early brain injury following subarachnoid hemorrhage via targeting TAK1-dependent MAPKs and NF-κB pathways.

Yan Zhou, Tao Tao, Guangjie Liu, Xuan Gao, Yongyue Gao, Zong Zhuang, Yue Lu, Han Wang, Wei Li, Lingyun Wu and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

34 citing papers in PubMed, 70 citations in OpenAlex.

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  5. medRxiv : the preprint server for health sciences · 2025
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  11. International journal of molecular sciences · 2025
    Article
  12. Review
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  15. Review
  16. Article
  17. Article
  18. Article
  19. The Role of Circular RNAs in Ischemic Stroke.Neurochemical research · 2023
    Review
  20. Article
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

12 authors at 1 institution in 1 country.

Yan ZhouDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Zhongshan Road 321, 210008, Nanjing, Jiangsu, People's Republic of China.
Tao TaoDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Zhongshan Road 321, 210008, Nanjing, Jiangsu, People's Republic of China.
Guangjie LiuDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Zhongshan Road 321, 210008, Nanjing, Jiangsu, People's Republic of China.
Xuan GaoDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Zhongshan Road 321, 210008, Nanjing, Jiangsu, People's Republic of China.
Yongyue GaoDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Zhongshan Road 321, 210008, Nanjing, Jiangsu, People's Republic of China.
Zong ZhuangDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Zhongshan Road 321, 210008, Nanjing, Jiangsu, People's Republic of China.
Yue LuDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Zhongshan Road 321, 210008, Nanjing, Jiangsu, People's Republic of China.ORCID 0000-0001-9111-5943
Han WangDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Clinical Medical College of Southern Medical University (Guangzhou), 210008, Nanjing, Jiangsu, People's Republic of China.
Wei LiDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Zhongshan Road 321, 210008, Nanjing, Jiangsu, People's Republic of China.
Lingyun WuDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Zhongshan Road 321, 210008, Nanjing, Jiangsu, People's Republic of China.
Dingding ZhangDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Zhongshan Road 321, 210008, Nanjing, Jiangsu, People's Republic of China. zhangding9856@126.com.
Chunhua HangDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Zhongshan Road 321, 210008, Nanjing, Jiangsu, People's Republic of China. hang_neurosurgery@163.com.
Nanjing Drum Tower Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neuronal apoptosis has an important role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). TRAF3 was reported as a promising therapeutic target for stroke management, which covered several neuronal apoptosis signaling cascades. Hence, the present study is aimed to determine whether downregulation of TRAF3 could be neuroprotective in SAH-induced EBI. An in vivo SAH model in mice was established by endovascular perforation. Meanwhile, primary cultured cortical neurons of mice treated with oxygen hemoglobin were applied to mimic SAH in vitro. Our results demonstrated that TRAF3 protein expression increased and expressed in neurons both in vivo and in vitro SAH models. TRAF3 siRNA reversed neuronal loss and improved neurological deficits in SAH mice, and reduced cell death in SAH primary neurons. Mechanistically, we found that TRAF3 directly binds to TAK1 and potentiates phosphorylation and activation of TAK1, which further enhances the activation of NF-κB and MAPKs pathways to induce neuronal apoptosis. Importantly, TRAF3 expression was elevated following SAH in human brain tissue and was mainly expressed in neurons. Taken together, our study demonstrates that TRAF3 is an upstream regulator of MAPKs and NF-κB pathways in SAH-induced EBI via its interaction with and activation of TAK1. Furthermore, the TRAF3 may serve as a novel therapeutic target in SAH-induced EBI.

Indexed as

AnimalsApoptosisBrain InjuriesDisease Models, AnimalHumansMaleMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesMAP Kinase Signaling SystemMiceMiddle AgedNeuronsNF-kappa BSignal TransductionSubarachnoid HemorrhageTNF Receptor-Associated Factor 3MAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesNF-kappa BTNF Receptor-Associated Factor 3TRAF3 protein, human

Identifiers

PMID33414375
PMCPMC7790824
OpenAlexW3175610182

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Registered trials

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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 OpenQuestion graph.