Evidence map›Paper›PMID 29252509›Full record

ArticleAnesthesiology2018

Dexmedetomidine Prevents Cognitive Decline by Enhancing Resolution of High Mobility Group Box 1 Protein-induced Inflammation through a Vagomimetic Action in Mice.

Jun Hu, Susana Vacas, Xiaomei Feng, David Lutrin, Yosuke Uchida, Ieng Kit Lai, Mervyn Maze

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

Article in Anesthesiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 4 pooled it
4.5field-weighted citation impact, top 4% 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

41 citing papers in PubMed, 4 syntheses or guidelines pooled it, 85 citations in OpenAlex.

  1. Appraisal of the Neuroprotective Effect of Dexmedetomidine: A Meta-Analysis.Advances in experimental medicine and biology · 2023
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  11. Clinical Use of Adrenergic Receptor Ligands in Acute Care Settings.Handbook of experimental pharmacology · 2024
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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

7 authors at 1 institution in 1 country.

Jun HuFrom the Department of Anesthesia and Perioperative Care and Center for Cerebrovascular Research, University of California, San Francisco, San Francisco, California (J.H., X.F., D.L., Y.U., I.K.L., M.M.); the Department of Anesthesia, Tongling People's Hospital, Tongling, People's Republic of China (J.H.); and the Department of Anesthesia and Perioperative Medicine, University of California, Los Angeles, Los Angeles, California (S.V.).
Susana Vacas
Xiaomei Feng
David Lutrin
Yosuke Uchida
Ieng Kit Lai
Mervyn Maze
University of California, San Francisco · US

Funding

Maladaptive Plasticity in Spinal Cord Injury: Cellular MechanismsR01NS088475 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERGUSON, ADAM R · 2015 to 2019
$1.7M
Cell type-specific influences on HHT pathogenesisR01HL122774 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SU, HUA · 2015 to 2018
$1.6M
Inflammation resolving mechanism dysregulation in postoperative cognitive declineR01GM104194 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MAZE, MERVYN · 2013 to 2016
$1.2M
NHLBI NIH HHS R01 HL122774NIGMS NIH HHS R01 GM104194NINDS NIH HHS R01 NS088475
6 · The paper itself

Abstract

backgroundInflammation initiated by damage-associated molecular patterns has been implicated for the cognitive decline associated with surgical trauma and serious illness. We determined whether resolution of inflammation mediates dexmedetomidine-induced reduction of damage-associated molecular pattern-induced cognitive decline.

methodsCognitive decline (assessed by trace fear conditioning) was induced with high molecular group box 1 protein, a damage-associated molecular pattern, in mice that also received blockers of neural (vagal) and humoral inflammation-resolving pathways. Systemic and neuroinflammation was assessed by proinflammatory cytokines.

resultsDamage-associated molecular pattern-induced cognitive decline and inflammation (mean ± SD) was reversed by dexmedetomidine (trace fear conditioning: 58.77 ± 8.69% vs. 41.45 ± 7.64%, P < 0.0001; plasma interleukin [IL]-1β: 7.0 ± 2.2 pg/ml vs. 49.8 ± 6.0 pg/ml, P < 0.0001; plasma IL-6: 3.2 ± 1.6 pg/ml vs. 19.5 ± 1.7 pg/ml, P < 0.0001; hippocampal IL-1β: 4.1 ± 3.0 pg/mg vs. 41.6 ± 8.0 pg/mg, P < 0.0001; hippocampal IL-6: 3.4 ± 1.3 pg/mg vs. 16.2 ± 2.7 pg/mg, P < 0.0001). Reversal by dexmedetomidine was prevented by blockade of vagomimetic imidazoline and α7 nicotinic acetylcholine receptors but not by α2 adrenoceptor blockade. Netrin-1, the orchestrator of inflammation-resolution, was upregulated (fold-change) by dexmedetomidine (lung: 1.5 ± 0.1 vs. 0.7 ± 0.1, P < 0.0001; spleen: 1.5 ± 0.2 vs. 0.6 ± 0.2, P < 0.0001), resulting in upregulation of proresolving (lipoxin-A4: 1.7 ± 0.2 vs. 0.9 ± 0.2, P < 0.0001) and downregulation of proinflammatory (leukotriene-B4: 1.0 ± 0.2 vs. 3.0 ± 0.3, P < 0.0001) humoral mediators that was prevented by α7 nicotinic acetylcholine receptor blockade.

conclusionsDexmedetomidine resolves inflammation through vagomimetic (neural) and humoral pathways, thereby preventing damage-associated molecular pattern-mediated cognitive decline.

Indexed as

AnimalsBlood-Brain BarrierCognitive DysfunctionDexmedetomidineHMGB1 ProteinImidazoline ReceptorsInflammationMaleMiceMice, Inbred C57BLNetrin-1Receptors, NicotinicVagus NerveChrna9 protein, mouseDexmedetomidineHMGB1 ProteinHMGB1 protein, mouseimidazoline I1 receptorsImidazoline ReceptorsNetrin-1Ntn1 protein, mouseReceptors, Nicotinic

Identifiers

PMID29252509
PMCPMC6445386
OpenAlexW2772218995

What OpenQuestion holds

Textmetadata
LicenceTDM
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.