Evidence map›Paper›PMID 37572732›Full record

ArticleJournal of advanced research2024

Lipidomic analysis identifies long-chain acylcarnitine as a target for ischemic stroke.

Xin-Xin Huang, Lei Li, Run-Hao Jiang, Jian-Bing Yu, Yu-Qin Sun, Jinjun Shan, Jin Yang, Juan Ji, Shu-Qi Cheng, Yin-Feng Dong and 4 more

Open access · goldAbstract read
In one paragraph

Article in Journal of advanced research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

34 citing papers in PubMed, 37 citations in OpenAlex.

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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

14 authors at 4 institutions in 1 country.

Xin-Xin HuangNeuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China; Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Lei LiNeuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
Run-Hao JiangDepartment of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jian-Bing YuNeuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
Yu-Qin SunNeuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
Jinjun ShanNanjing University of Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Jin YangNeuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
Juan JiNeuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
Shu-Qi ChengNeuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
Yin-Feng DongNanjing University of Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Xi-Yue ZhangNeuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
Hai-Bin ShiDepartment of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Sheng LiuDepartment of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: liusheng@njmu.edu.cn.
Xiu-Lan SunNeuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China; Nanjing University of Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: xiulans@njmu.edu.cn.
Nanjing Medical University · CNJiangsu Province Hospital · CNNanjing University of Chinese Medicine · CNZhongda Hospital Southeast University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionLipid metabolism dysfunction is widely involved in the pathological process of acute ischemic stroke (AIS). The coordination of lipid metabolism between neurons and astrocytes is of great significance. However, the full scope of lipid dynamic changes and the function of key lipids during AIS remain unknown. Hence, identifying lipid alterations and characterizing their key roles in AIS is of great importance.

methodsUntargeted and targeted lipidomic analyses were applied to profile lipid changes in the ischemic penumbra and peripheral blood of transient middle cerebral artery occlusion (tMCAO) mice as well as the peripheral blood of AIS patients. Infarct volume and neurological deficits were assessed after tMCAO. The cell viability and dendritic complexity of primary neurons were evaluated by CCK8 assay and Sholl analysis. Seahorse, MitoTracker Green, tetramethyl rhodamine methyl ester (TMRM), 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSOX were used as markers of mitochondrial health. Fluorescent and isotopic free fatty acid (FFA) pulse-chase assays were used to track FFA flux in astrocytes.

resultsLong-chain acylcarnitines (LCACs) were the lipids with the most dramatic changes in the ischemic penumbra and peripheral blood of tMCAO mice. LCACs were significantly elevated on admission in AIS patients and associated with poor outcomes in AIS patients. Increasing LCACs through a bolus administration of palmitoylcarnitine amplified stroke injury, while decreasing LCACs by overexpressing carnitine palmitoyltransferase 2 (CPT2) ameliorated stroke injury. Palmitoylcarnitine aggravated astrocytic mitochondrial damage after OGD/R, while CPT2 overexpression in astrocytes ameliorated cocultured neuron viability. Further study revealed that astrocytes stimulated by OGD/R liberated FFAs from lipid droplets into mitochondria to form LCACs, resulting in mitochondrial damage and lowered astrocytic metabolic support and thereby aggravated neuronal damage.

conclusionLCACs could accumulate and damage neurons by inducing astrocytic mitochondrial dysfunction in AIS. LCACs play a crucial role in the pathology of AIS and are novel promising diagnostic and prognostic biomarkers for AIS.

Indexed as

AstrocytesCarnitineIschemic StrokeLipid MetabolismLipidomicsNeuronsAgedAnimalsBrain IschemiaDisease Models, AnimalFemaleHumansInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLacylcarnitineCarnitineAstrocytic mitochondrialBiomarkerIschemic strokeLipid dropletLong-chain acylcarnitine

Identifiers

PMID37572732
PMCPMC11258661
OpenAlexW4385728439

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.