Evidence map›Paper›PMID 39004380›Full record

ArticleBiochimica et biophysica acta. Molecular basis of disease2024

Thyroid hormone T4 mitigates traumatic brain injury in mice by dynamically remodeling cell type specific genes, pathways, and networks in hippocampus and frontal cortex.

Guanglin Zhang, Graciel Diamante, In Sook Ahn, Victoria Palafox-Sanchez, Jenny Cheng, Michael Cheng, Zhe Ying, Susanna Sue-Ming Wang, Kevin Daniel Abuhanna, Nguyen Phi and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochimica et biophysica acta. Molecular basis of disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
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

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Single-cell RNA sequencing in stroke and traumatic brain injury: Current achievements, challenges and future perspectives on transcriptomic profiling.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
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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

18 authors.

Guanglin ZhangDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Graciel DiamanteDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
In Sook AhnDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Victoria Palafox-SanchezDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jenny ChengDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular, Cellular and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Michael ChengDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Zhe YingDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Susanna Sue-Ming WangDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Kevin Daniel AbuhannaDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Nguyen PhiDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Douglas ArnesonDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Ingrid CelyDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Kayla ArellanoDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Ning WangDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Shujing ZhangDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Chao PengDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Mary S. Easton Center for Alzheimer's Research, University of California, Los Angeles, Los Angeles, CA, USA.
Fernando Gomez-PinillaDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurosurgery, University of California, Los Angeles, Los Angeles, CA 90095, USA; Brain Injury Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Xia YangDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular, Cellular and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: xyang123@ucla.edu.

Funding

Precision Medicine Approach: Using genomic information to guide TBI treatmentR01NS111378 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GOMEZ-PINILLA, FERNANDO, YANG, XIA · 2020 to 2024
$2.9M
Spatiotemporal Molecular Substrates of TBI at Single Cell ResolutionR01NS117148 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GOMEZ-PINILLA, FERNANDO, WOLLMAN, ROY · 2020 to 2024
$2.8M
NINDS NIH HHS R01 NS111378NINDS NIH HHS R01 NS117148
6 · The paper itself

Abstract

The complex pathology of mild traumatic brain injury (mTBI) is a main contributor to the difficulties in achieving a successful therapeutic regimen. Thyroxine (T4) administration has been shown to prevent the cognitive impairments induced by mTBI in mice but the mechanism is poorly understood. To understand the underlying mechanism, we carried out a single cell transcriptomic study to investigate the spatiotemporal effects of T4 on individual cell types in the hippocampus and frontal cortex at three post-injury stages in a mouse model of mTBI. We found that T4 treatment altered the proportions and transcriptomes of numerous cell types across tissues and timepoints, particularly oligodendrocytes, astrocytes, and microglia, which are crucial for injury repair. T4 also reversed the expression of mTBI-affected genes such as Ttr, mt-Rnr2, Ggn12, Malat1, Gnaq, and Myo3a, as well as numerous pathways such as cell/energy/iron metabolism, immune response, nervous system, and cytoskeleton-related pathways. Cell-type specific network modeling revealed that T4 mitigated select mTBI-perturbed dynamic shifts in subnetworks related to cell cycle, stress response, and RNA processing in oligodendrocytes. Cross cell-type ligand-receptor networks revealed the roles of App, Hmgb1, Fn1, and Tnf in mTBI, with the latter two ligands having been previously identified as TBI network hubs. mTBI and/or T4 signature genes were enriched for human genome-wide association study (GWAS) candidate genes for cognitive, psychiatric and neurodegenerative disorders related to mTBI. Our systems-level single cell analysis elucidated the temporal and spatial dynamic reprogramming of cell-type specific genes, pathways, and networks, as well as cell-cell communications as the mechanisms through which T4 mitigates cognitive dysfunction induced by mTBI.

Indexed as

Brain Injuries, TraumaticFrontal LobeHippocampusThyroxineAnimalsAstrocytesBrain ConcussionDisease Models, AnimalGene Regulatory NetworksMaleMiceMice, Inbred C57BLMicrogliaOligodendrogliaSignal TransductionTranscriptomeThyroxineFrontal cortexGenome-wide association study (GWAS)hippocampusMild traumatic brain injury (mTBI)Single cell RNA sequencing (scRNA-seq)Thyroxine (T4)

Identifiers

PMID39004380
PMCPMC12962868

What OpenQuestion holds

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LicenceCC BY-NC
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.