Evidence map›Paper›PMID 34225752›Full record

ArticleJournal of neuroinflammation2021

Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response.

Brittany P Todd, Michael S Chimenti, Zili Luo, Polly J Ferguson, Alexander G Bassuk, Elizabeth A Newell

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 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

72 citing papers in PubMed, 101 citations in OpenAlex.

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  15. 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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12 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

6 authors at 1 institution in 1 country.

Brittany P ToddMedical Scientist Training Program, University of Iowa, Iowa City, IA, USA.
Michael S ChimentiIowa Institute of Human Genetics, Bioinformatics Division, University of Iowa, Iowa City, IA, USA.
Zili LuoDepartment of Pediatrics, University of Iowa, Iowa City, IA, USA.
Polly J FergusonDepartment of Pediatrics, University of Iowa, Iowa City, IA, USA.
Alexander G BassukDepartment of Pediatrics, University of Iowa, Iowa City, IA, USA. alexander-bassuk@uiowa.edu.
Elizabeth A NewellDepartment of Pediatrics, University of Iowa, Iowa City, IA, USA. elizabeth-newell@uiowa.edu.ORCID http://orcid.org/0000-0002-1476-033X
University of Iowa · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007337 · NIGMS · UNIVERSITY OF IOWA · PI GEYER, PAMELA K., LENTZ, STEVEN R · 1985 to 2020
$15.9M
Medical Scientist Training ProgramT32GM139776 · NIGMS · UNIVERSITY OF IOWA · PI Gordon F Buchanan · 2021 to 2026
$6.4M
Exploring Novel Epilepsy PathwaysR01NS098590 · NINDS · UNIVERSITY OF IOWA · PI BASSUK, ALEXANDER G · 2016 to 2020
$2.8M
Astrocyte-Specific IL-1RI Signaling Effects Following Traumatic Brain InjuryK08NS110829 · NINDS · UNIVERSITY OF IOWA · PI NEWELL, ELIZABETH · 2019 to 2023
$938k
NIGMS NIH HHS T32 GM007337NIGMS NIH HHS T32 GM139776NIH HHS R01AR059730NIH HHS R01NS098590NINDS NIH HHS K08 NS110829NINDS NIH HHS K08NS110829NINDS NIH HHS R01 NS098590
6 · The paper itself

Abstract

backgroundTraumatic brain injury (TBI) is a leading cause of death and disability that lacks neuroprotective therapies. Following a TBI, secondary injury response pathways are activated and contribute to ongoing neurodegeneration. Microglia and astrocytes are critical neuroimmune modulators with early and persistent reactivity following a TBI. Although histologic glial reactivity is well established, a precise understanding of microglia and astrocyte function following trauma remains unknown.

methodsAdult male C57BL/6J mice underwent either fluid percussion or sham injury. RNA sequencing of concurrently isolated microglia and astrocytes was conducted 7 days post-injury to evaluate cell-type-specific transcriptional responses to TBI. Dual in situ hybridization and immunofluorescence were used to validate the TBI-induced gene expression changes in microglia and astrocytes and to identify spatial orientation of cells expressing these genes. Comparative analysis was performed between our glial transcriptomes and those from prior reports in mild TBI and other neurologic diseases to determine if severe TBI induces unique states of microglial and astrocyte activation.

resultsOur findings revealed sustained, lineage-specific transcriptional changes in both microglia and astrocytes, with microglia showing a greater transcriptional response than astrocytes at this subacute time point. Microglia and astrocytes showed overlapping enrichment for genes related to type I interferon signaling and MHC class I antigen presentation. The microglia and astrocyte transcriptional response to severe TBI was distinct from prior reports in mild TBI and other neurodegenerative and neuroinflammatory diseases.

conclusionConcurrent lineage-specific analysis revealed novel TBI-specific transcriptional changes; these findings highlight the importance of cell-type-specific analysis of glial reactivity following TBI and may assist with the identification of novel, targeted therapies.

Indexed as

AnimalsAstrocytesBrain Injuries, TraumaticInterferon Type IMaleMiceMice, Inbred C57BLMicrogliaTranscriptomeInterferon Type IAstrocytesMicrogliaTraumatic brain injuryType I interferon

Identifiers

PMID34225752
PMCPMC8259035
OpenAlexW3183010393

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.