Evidence map›Paper›PMID 38649772›Full record

ArticleClinical and translational medicine2024

ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.

Jonathan Z Pan, Zhanqiang Wang, Wei Sun, Peipei Pan, Wei Li, Yongtao Sun, Shoulin Chen, Amity Lin, Wulin Tan, Liangliang He and 38 more

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

Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
6.7field-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

13 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
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  4. Nerve tissue model on a micropatterned surface: Axon guidance and neural regeneration.Journal of materials science. Materials in medicine · 2025
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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

48 authors at 5 institutions in 2 countries.

Jonathan Z PanDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Zhanqiang WangDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Wei SunDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Peipei PanDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Wei LiDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Yongtao SunDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Shoulin ChenDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Amity LinDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Wulin TanDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Liangliang HeDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Jacob GreeneMedical School, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0002-0834-1024
Virginia YaoDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Lijun AnDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Rich LiangDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Qifeng LiDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Jessica YuDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Lingyi ZhangDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Nikolaos KyritsisDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Xuan Duong FernandezDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Sara MoncivaisDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Esmeralda MendozaDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Pamela FungDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Gongming WangDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Xinhuan NiuDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Qihang DuDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Zhaoyang XiaoDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Yuwen ChangDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Peiyuan LvDepartment of Anesthesiology, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
J Russell HuieDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Abel Torres-EspinDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Adam R FergusonDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Debra D HemmerleDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Jason F TalbottDepartment of Radiology, University of California San Francisco, San Francisco, California, USA.
Philip R WeinsteinDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Lisa U PascualDepartment of Orthopedic Surgery, Orthopaedic Trauma Institute, University of California San Francisco, San Francisco, California, USA.
Vineeta SinghDepartment of Neurology, University of California San Francisco, San Francisco, California, USA.
Anthony M DiGiorgioDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Rajiv SaigalDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
William D WhetstoneDepartment of Emergency Medicine, University of California San Francisco, San Francisco, California, USA.
Geoffrey T ManleyDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Sanjay S DhallDepartment of Neurosurgery, Harbor UCLA Medical Center, Torrance, California, USA.
Jacqueline C BresnahanDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Mervyn MazeDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Xiangning JiangDepartment of Neurology, University of California San Francisco, San Francisco, California, USA.
Neel S SinghalDepartment of Neurology, University of California San Francisco, San Francisco, California, USA.
Michael S BeattieDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Hua SuDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Zhonghui GuanDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0001-5992-8370
University of California, San Francisco · USShandong University · CNHebei Medical University · CNNanchang University · CNUCLA Medical Center · US

Funding

Regulation of Nerve Injury-induced Gene Expression in Neuropathic PainR01NS100801 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GUAN, ZHONGHUI · 2017 to 2021
$1.7M
NINDS NIH HHS R01 NS100801NINDS NIH HHS R01NS100801
6 · The paper itself

Abstract

backgroundAlthough many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions.

methodsIn animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits.

resultsActivating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function.

conclusionsATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. HIGHLIGHTS: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.

Indexed as

Activating Transcription Factor 3BiomarkersIschemic StrokeNeuronsSpinal Cord InjuriesAnimalsDisease Models, AnimalFemaleHumansMaleMiceMice, KnockoutActivating Transcription Factor 3ATF3 protein, humanAtf3 protein, mouseBiomarkersactivating transcription factor 3 (ATF3)biomarkerneuronal injuryneuroprotectionspinal cord injurystroke

Identifiers

PMID38649772
PMCPMC11035380
OpenAlexW4395052079

What Socratic holds

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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 Socratic graph.