Evidence map›Paper›PMID 39696348›Full record

ArticleJournal of neuroinflammation2024

Microglia in the aged brain develop a hypoactive molecular phenotype after surgery.

Zhuoran Yin, Anna K Leonard, Carl M Porto, Zhongcong Xie, Sebastian Silveira, Deborah J Culley, Oleg Butovsky, Gregory Crosby

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

8 authors.

Zhuoran Yin *Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Anna K Leonard *Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Carl M PortoDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Zhongcong XieDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Sebastian SilveiraDepartment of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Deborah J CulleyDepartment of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Oleg ButovskyDepartment of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Gregory CrosbyDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA, USA. gcrosby@bwh.harvard.edu.

Funding

Targeting the miR-155 and APOE-TREM2 pathways to restore dysfunctional microglia in Alzheimer’s diseaseR01AG054672 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI BUTOVSKY, OLEG, IKEZU, TSUNEYA · 2017 to 2021
$4.1M
Preoperative Occult Neurodegeneration and Postoperative DeliriumR01AG071741 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI CROSBY, GREGORY, CULLEY, DEBORAH J · 2022 to 2025
$3.5M
Microglial mechanisms of postoperative CNS inflammation and cognitive declineR01AG051812 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI BUTOVSKY, OLEG, CROSBY, GREGORY · 2016 to 2020
$2.7M
General Anesthesia and Alzheimer's Disease NeuropathogenesisRF1AG070761 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI XIE, ZHONGCONG · 2020 to 2020
$1.9M
Circulating Extracellular Vesicles as Biomarkers of Postoperative DeliriumR21AG061696 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI CROSBY, GREGORY · 2019 to 2020
$492k
BrightFocus Foundation 2020A016806National Institutes of Health,United States R01AG054672National Institutes of Health,United States R01AG071741National Institutes of Health,United States R21AG061696NIA NIH HHS R01 AG051812NIA NIH HHS R01 AG054672NIA NIH HHS R01 AG071741NIA NIH HHS R21 AG061696NIA NIH HHS RF1 AG070761NIH HHS 5R01AG051812NIH HHS NIARF1AG070761
6 · The paper itself

Abstract

backgroundMicroglia, the resident immune cells of the brain, play a crucial role in maintaining homeostasis in the central nervous system (CNS). However, they can also contribute to neurodegeneration through their pro-inflammatory properties and phagocytic functions. Acute post-operative cognitive deficits have been associated with inflammation, and microglia have been implicated primarily based on morphological changes. We investigated the impact of surgery on the microglial transcriptome to test the hypothesis that surgery produces an age-dependent pro-inflammatory phenotype in these cells.

methodsThree-to-five and 20-to-22-month-old C57BL/6 mice were anesthetized with isoflurane for an abdominal laparotomy, followed by sacrifice either 6 or 48 h post-surgery. Age-matched controls were exposed to carrier gas. Cytokine concentrations in plasma and brain tissue were evaluated using enzyme-linked immunosorbent assays (ELISA). Iba1

resultsSurgery induced an elevation in plasma cytokines in both age groups. Notably, increased CCL2 was observed in the brain post-surgery, with a greater change in old compared to young mice. Age, rather than the surgical procedure, increased Iba1 immunoreactivity and the number of Iba1

conclusionsWhile anesthesia and surgery induce pro-inflammatory changes in the plasma and brain of mice, microglia adopt a homeostatic molecular phenotype following surgery. This effect seems to be more pronounced in aged mice and is transient. These results challenge the prevailing assumption that surgery activates microglia in the aged brain.

Indexed as

AgingBrainMice, Inbred C57BLMicrogliaPhenotypeAnimalsCytokinesMaleMiceCytokinesAgingMicrogliaNeuroinflammationSurgery

Identifiers

PMID39696348
PMCPMC11658347

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Registered trials

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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.