Evidence map›Paper›PMID 33879157›Full record

ArticleJournal of neuroinflammation2021

Inhibition of MLKL-dependent necroptosis via downregulating interleukin-1R1 contributes to neuroprotection of hypoxic preconditioning in transient global cerebral ischemic rats.

Lixuan Zhan, Xiaomei Lu, Wensheng Xu, Weiwen Sun, En Xu

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

16 citing papers in PubMed, 20 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

5 authors at 2 institutions in 1 country.

Lixuan Zhan *Institute of Neurosciences and Department of Neurology of The Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changgang Dong RD, Guangzhou, 510260, People's Republic of China.
Xiaomei Lu *Institute of Neurosciences and Department of Neurology of The Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changgang Dong RD, Guangzhou, 510260, People's Republic of China.
Wensheng XuInstitute of Neurosciences and Department of Neurology of The Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changgang Dong RD, Guangzhou, 510260, People's Republic of China.
Weiwen SunInstitute of Neurosciences and Department of Neurology of The Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changgang Dong RD, Guangzhou, 510260, People's Republic of China.
En XuInstitute of Neurosciences and Department of Neurology of The Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changgang Dong RD, Guangzhou, 510260, People's Republic of China. enxu@163.net.
Second Affiliated Hospital of Guangzhou Medical University · CNGuangzhou Medical University · CN

Funding

National Natural Science Foundation of China 81971124National Natural Science Foundation of China 82071281Science and Technology Program of Guangzhou, China 202002030072
6 · The paper itself

Abstract

backgroundOur previous study indicated that hypoxic preconditioning reduced receptor interacting protein (RIP) 3-mediated necroptotic neuronal death in hippocampal CA1 of adult rats after transient global cerebral ischemia (tGCI). Although mixed lineage kinase domain-like (MLKL) has emerged as a crucial molecule for necroptosis induction downstream of RIP3, how MLKL executes necroptosis is not yet well understood. In this study, we aim to elucidate the molecular mechanism underlying hypoxic preconditioning that inactivates MLKL-dependent neuronal necroptosis after tGCI.

methodsTransient global cerebral ischemia was induced by the four-vessel occlusion method. Twenty-four hours before ischemia, rats were exposed to systemic hypoxia with 8% O

resultsHypoxic preconditioning decreased the phosphorylation of MLKL both in neurons and microglia of CA1 after tGCI. The knockdown of MLKL with siRNA decreased the expression of p-MLKL and exerted neuroprotective effects after tGCI, whereas treatment with lentiviral delivery of MLKL showed opposite results. Mechanistically, hypoxic preconditioning or MLKL siRNA attenuated the RIP3-p-MLKL interaction, reduced the plasma membrane translocation of p-MLKL, and blocked Ca

conclusionsThese data support that the inhibition of MLKL-dependent neuronal necroptosis through downregulating IL-1R1 contributes to neuroprotection of hypoxic preconditioning against tGCI.

Indexed as

Down-RegulationNecroptosisNeuroprotectionAnimalsBrainCA1 Region, HippocampalGene Knockdown TechniquesHypoxiaIschemic Attack, TransientIschemic PreconditioningMaleNeuroprotective AgentsPhosphorylationProtein KinasesRatsRats, WistarMLKL protein, ratNeuroprotective AgentsProtein KinasesReceptor-Interacting Protein Serine-Threonine KinasesReceptors, Interleukin-1 Type ICalcium ion influxCerebral ischemiaHypoxic preconditioningIL-1R1MLKLNecroptosisPlasma membrane translocation

Identifiers

PMID33879157
PMCPMC8056617
OpenAlexW3155511461

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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.