Evidence map›Paper›PMID 36100985›Full record

ArticleCurrent neurovascular research2022

Simvastatin Upregulates Lipoxin A4 and Accelerates Neuroinflammation Resolution After Intracerebral Hemorrhage.

Jianbo Zhang, Na Hao, Wei Li, Qianwei Chen, Zhi Chen, Hua Feng, Yao Wu, Xia Shi

Open access · greenAbstract read
In one paragraph

Article in Current neurovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Fpr2 exacerbatesFrontiers in immunology · 2023
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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

8 authors at 5 institutions in 1 country.

Jianbo ZhangDepartment of Neurosurgery, General Hospital of South Theater Command, Guangdong, 510030, China.
Na HaoDepartment of Orthopedics, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400000, China.
Wei LiDepartment of Laboratory Medicine, Western Theater Command Air Force Hospital, Chengdu, 610065, China.
Qianwei ChenDepartment of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Zhi ChenDepartment of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Hua FengDepartment of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Yao WuDepartment of Neurosurgery, Chongqing University Three Gorges Hospital, Chongqing, 404031, China.
Xia ShiDepartment of Nutrition, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Army Medical University · CNSouthwest Hospital · CNChongqing University · CNFirst People's Hospital of Chongqing · CNGeneral Hospital of Guangzhou Military Command · CN

Funding

China Postdoctoral Science Foundation 2020M673651DZ Hospital Construction Project by Southwest Hospital 2022DZXDX001National Natural Science Foundation of China 81701147
6 · The paper itself

Abstract

backgroundPrevious studies have demonstrated that statins can relieve inflammatory brain injury after intracerebral hemorrhage (ICH), but the mechanisms remain poorly characterized. This study aims to test whether simvastatin exerts an anti-inflammatory effect by regulating the proresolving mediators.

methodsFirst, male Sprague-Dawley rats had an injection of 200 μL autologous blood. Then, rats were randomly divided into groups treated with simvastatin (i.p. 2 mg/kg) or vehicle. Next, all rats underwent pro-resolving mediator lipoxin A4 (LXA4) level detection, flow cytometric, immunofluorescence, brain edema measurement, neurological scoring and western blot analysis.

resultsWe found that simvastatin significantly increased the plasma level of LXA4, an endogenous formyl-peptide receptor 2 (FPR2) agonist, in the early stage of ICH. Consistent with the effect of simvastatin, exogenous LXA4 administration also promoted apoptosis of the circulating neutrophils, reduced neutrophils brain infiltration, and ameliorated inflammatory brain injury after ICH. In addition, similar to simvastatin, exogenous LXA4 markedly decreased the level of phosphorylated p38 mitogen-activated protein kinase (MAPK) and the apoptosis-related proteins myeloid cell leukemia 1(Mcl-1)/Bax ratio (a decreased ratio represents the induction of apoptosis) in circulating neutrophils isolated from ICH rats. Notably, all of the aforementioned effects of simvastatin on ICH were significantly abolished by Boc-2, a selective antagonist of FPR2. Moreover, simvastatin led to a similar Mcl-1/Bax ratio reduction as SB203580 (a p38 MAPK inhibitor), but it was abolished by P79350 (a p38 MAPK agonist).

conclusionCollectively, these results suggest that simvastatin ameliorates ICH-mediated inflammatory brain injury, possibly by upregulating the level of pro-resolving mediator LXA4 and further stimulating the FPR2/p38 MAPK signaling pathway.

Indexed as

Brain InjuriesNeuroinflammatory DiseasesAnimalsbcl-2-Associated X ProteinCerebral HemorrhageLipoxinsMaleMyeloid Cell Leukemia Sequence 1 Proteinp38 Mitogen-Activated Protein KinasesRatsRats, Sprague-DawleySimvastatinbcl-2-Associated X Proteinlipoxin A4LipoxinsMyeloid Cell Leukemia Sequence 1 Proteinp38 Mitogen-Activated Protein KinasesSimvastatinapoptosisformyl-peptide receptor 2inflammationIntracerebral hemorrhagelipoxin A4neutrophilsstatins

Identifiers

PMID36100985
PMCPMC9982195
OpenAlexW4295760563

What OpenQuestion holds

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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.