Evidence map›Paper›PMID 31440141›Full record

ArticleFrontiers in cellular neuroscience2019

Time-Dependent Changes in Microglia Transcriptional Networks Following Traumatic Brain Injury.

Saef Izzy, Qiong Liu, Zhou Fang, Sevda Lule, Limin Wu, Joon Yong Chung, Aliyah Sarro-Schwartz, Alexander Brown-Whalen, Caroline Perner, Suzanne E Hickman and 4 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in cellular neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
7.9field-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

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.

  1. Pooled it
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  13. Imaging a concussion and the ensuing immune response at the blood-brain barrier.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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  15. Article
  16. Article
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  18. Single-cell mNature neuroscience · 2024
    Article
  19. Article
  20. Review

9 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

14 authors at 6 institutions in 2 countries.

Saef IzzyDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Qiong LiuDepartment of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Zhou FangHarvard Medical School, Boston, MA, United States.
Sevda LuleMassachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States.
Limin WuMassachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States.
Joon Yong ChungMassachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States.
Aliyah Sarro-SchwartzDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Alexander Brown-WhalenCenter for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Caroline PernerCenter for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Suzanne E HickmanCenter for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
David L KaplanDepartment of Biomedical Engineering, Tufts University, Medford, MA, United States.
Nikolaos A PatsopoulosHarvard Medical School, Boston, MA, United States.
Joseph El KhouryCenter for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Michael J WhalenMassachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States.
Harvard University · USMassachusetts General Hospital · USBrigham and Women's Hospital · USBroad Institute · USFudan University · CNTufts University · US

Funding

The Neuroimmune System in Alzheimer's DiseaseRF1AG051506 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI EL-KHOURY, JOSEPH EL · 2015 to 2015
$3.8M
Functional three dimensional brain-like tissues to study mechanisms of traumatic brain injuryR01NS092847 · NINDS · TUFTS UNIVERSITY MEDFORD · PI KAPLAN, DAVID L. · 2015 to 2019
$1.8M
NIA NIH HHS RF1 AG051506NINDS NIH HHS R01 NS092847
6 · The paper itself

Abstract

The neuroinflammatory response to traumatic brain injury (TBI) is critical to both neurotoxicity and neuroprotection, and has been proposed as a potentially modifiable driver of secondary injury in animal and human studies. Attempts to broadly target immune activation have been unsuccessful in improving outcomes, in part because the precise cellular and molecular mechanisms driving injury and outcome at acute, subacute, and chronic time points after TBI remain poorly defined. Microglia play a critical role in neuroinflammation and their persistent activation may contribute to long-term functional deficits. Activated microglia are characterized by morphological transformation and transcriptomic changes associated with specific inflammatory states. We analyzed the temporal course of changes in inflammatory genes of microglia isolated from injured brains at 2, 14, and 60 days after controlled cortical impact (CCI) in mice, a well-established model of focal cerebral contusion. We identified a time dependent, injury-associated change in the microglial gene expression profile toward a reduced ability to sense tissue damage, perform housekeeping, and maintain homeostasis in the early stages following CCI, with recovery and transition to a specialized inflammatory state over time. This later state starts at 14 days post-injury and is characterized by a biphasic pattern of IFNγ, IL-4, and IL-10 gene expression changes, with concurrent proinflammatory and anti-inflammatory gene changes. Our transcriptomic data sets are an important step to understand microglial role in TBI pathogenesis at the molecular level and identify common pathways that affect outcome. More studies to evaluate gene expression at the single cell level and focusing on subacute and chronic timepoint are warranted.

Indexed as

micemicroglianeurodegenerationneuroimmunologyneuroinflammationtranscriptometraumatic brain injury

Identifiers

PMID31440141
PMCPMC6694299
OpenAlexW2968346446

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.