Evidence map›Paper›PMID 33402181›Full record

ArticleJournal of neuroinflammation2021

Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury.

Haijian Wu, Jingwei Zheng, Shenbin Xu, Yuanjian Fang, Yingxi Wu, Jianxiong Zeng, Anwen Shao, Ligen Shi, Jianan Lu, Shuhao Mei and 5 more

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
175citing papers in PubMed, 1 pooled it
23.7field-weighted citation impact, top 1% 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

175 citing papers in PubMed, 1 synthesis or guideline pooled it, 353 citations in OpenAlex.

  1. Pooled it
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  7. Defective efferocytosis in diabetes: molecular mechanisms and emerging therapeutic strategies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
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  12. [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026
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115 more citing papers are in PubMed but not listed here.

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 4 institutions in 2 countries.

Haijian WuDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Jingwei ZhengDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Shenbin XuDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Yuanjian FangDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Yingxi WuCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, 1501 San Pablo Street, Los Angeles, CA, 90089, USA.
Jianxiong ZengCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, 1501 San Pablo Street, Los Angeles, CA, 90089, USA.
Anwen ShaoDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Ligen ShiDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Jianan LuDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Shuhao MeiDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Xiaoyu WangDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Xinying GuoCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, 1501 San Pablo Street, Los Angeles, CA, 90089, USA.
Yirong WangDepartment of Neurosurgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Zhen ZhaoCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, 1501 San Pablo Street, Los Angeles, CA, 90089, USA. zzhao@usc.edu.
Jianmin ZhangDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China. zjm135@zju.edu.cn.ORCID http://orcid.org/0000-0002-3184-1502
Second Affiliated Hospital of Zhejiang University · CNUniversity of Southern California · USChinese Institute for Brain Research · CNSir Run Run Shaw Hospital · CN

Funding

BrightFocus Foundation A2019218SKey Program of Science and Technology Development of Zhejiang 2017C03021National Key Research and Development Program of China 2017YFC1308500National Natural Science Foundation of China 81701214National Natural Science Foundation of China 81870916
6 · The paper itself

Abstract

backgroundTraumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial/macrophage activation and neuroinflammation are key cellular events following TBI, but the regulatory and functional mechanisms are still not well understood. Myeloid-epithelial-reproductive tyrosine kinase (Mer), a member of the Tyro-Axl-Mer (TAM) family of receptor tyrosine kinases, regulates multiple features of microglial/macrophage physiology. However, its function in regulating the innate immune response and microglial/macrophage M1/M2 polarization in TBI has not been addressed. The present study aimed to evaluate the role of Mer in regulating microglial/macrophage M1/M2 polarization and neuroinflammation following TBI.

methodsThe controlled cortical impact (CCI) mouse model was employed. Mer siRNA was intracerebroventricularly administered, and recombinant protein S (PS) was intravenously applied for intervention. The neurobehavioral assessments, RT-PCR, Western blot, magnetic-activated cell sorting, immunohistochemistry and confocal microscopy analysis, Nissl and Fluoro-Jade B staining, brain water content measurement, and contusion volume assessment were performed.

resultsMer is upregulated and regulates microglial/macrophage M1/M2 polarization and neuroinflammation in the acute stage of TBI. Mechanistically, Mer activates the signal transducer and activator of transcription 1 (STAT1)/suppressor of cytokine signaling 1/3 (SOCS1/3) pathway. Inhibition of Mer markedly decreases microglial/macrophage M2-like polarization while increases M1-like polarization, which exacerbates the secondary brain damage and sensorimotor deficits after TBI. Recombinant PS exerts beneficial effects in TBI mice through Mer activation.

conclusionsMer is an important regulator of microglial/macrophage M1/M2 polarization and neuroinflammation, and may be considered as a potential target for therapeutic intervention in TBI.

Indexed as

AnimalsBrain Injuries, TraumaticCell Polarityc-Mer Tyrosine KinaseFemaleInflammation MediatorsMacrophage ActivationMacrophagesMaleMiceMice, Inbred C57BLMicrogliac-Mer Tyrosine KinaseInflammation MediatorsMertk protein, mouseM1/M2 polarizationMerMicroglia/macrophageNeuroinflammationTBI

Identifiers

PMID33402181
PMCPMC7787000
OpenAlexW3115422892

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LicenceCC BY
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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.