Evidence map›Paper›PMID 35951114›Full record

ArticleCellular and molecular life sciences : CMLS2022

Systems spatiotemporal dynamics of traumatic brain injury at single-cell resolution reveals humanin as a therapeutic target.

Douglas Arneson, Guanglin Zhang, In Sook Ahn, Zhe Ying, Graciel Diamante, Ingrid Cely, Victoria Palafox-Sanchez, Fernando Gomez-Pinilla, Xia Yang

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

Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

30 citing papers in PubMed, 34 citations in OpenAlex.

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  9. CSF1R and IL1R1 inhibitors synergistically attenuate the early pathogenesis of traumatic brain injury in mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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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

9 authors at 2 institutions in 1 country.

Douglas Arneson *Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Guanglin Zhang *Department 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.
Zhe YingDepartment 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.
Ingrid CelyDepartment 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.
Fernando Gomez-PinillaDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA. fgomezpi@ucla.edu.
Xia YangDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA. xyang123@ucla.edu.ORCID http://orcid.org/0000-0002-3971-038X
University of California, Los Angeles · USQB3 · US

Funding

Restoration of Homeostasis After Brain TraumaR01NS050465 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GOMEZ-PINILLA, FERNANDO · 2005 to 2019
$5.5M
Strategy to Potentiate Rehabilitation after TBIR01NS116383 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HARRIS, NEIL · 2021 to 2025
$3.0M
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
Biomedical Big Data Training GrantT32CA201160 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PELLEGRINI, MATTEO · 2015 to 2015
$264k
NCI NIH HHS T32 CA201160NINDS NIH HHS R01 NS050465NINDS NIH HHS R01 NS111378NINDS NIH HHS R01 NS116383NINDS NIH HHS R01 NS117148
6 · The paper itself

Abstract

backgroundThe etiology of mild traumatic brain injury (mTBI) remains elusive due to the tissue and cellular heterogeneity of the affected brain regions that underlie cognitive impairments and subsequent neurological disorders. This complexity is further exacerbated by disrupted circuits within and between cell populations across brain regions and the periphery, which occur at different timescales and in spatial domains.

methodsWe profiled three tissues (hippocampus, frontal cortex, and blood leukocytes) at the acute (24-h) and subacute (7-day) phases of mTBI at single-cell resolution.

resultsWe demonstrated that the coordinated gene expression patterns across cell types were disrupted and re-organized by TBI at different timescales with distinct regional and cellular patterns. Gene expression-based network modeling implied astrocytes as a key regulator of the cell-cell coordination following mTBI in both hippocampus and frontal cortex across timepoints, and mt-Rnr2, which encodes the mitochondrial peptide humanin, as a potential target for intervention based on its broad regional and dynamic dysregulation following mTBI. Treatment of a murine mTBI model with humanin reversed cognitive impairment caused by mTBI through the restoration of metabolic pathways within astrocytes.

conclusionsOur results offer a systems-level understanding of the dynamic and spatial regulation of gene programs by mTBI and pinpoint key target genes, pathways, and cell circuits that are amenable to therapeutics.

Indexed as

Brain InjuriesBrain Injuries, TraumaticAnimalsBrainHippocampusIntracellular Signaling Peptides and ProteinsMicehumaninIntracellular Signaling Peptides and ProteinsAstrocytesHumaninMt-Rnr2Single-cell RNA sequencingTBITraumatic brain injury

Identifiers

PMID35951114
PMCPMC9372016
OpenAlexW4290973097

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.