Evidence map›Paper›PMID 32343048›Full record

ArticleCNS neuroscience & therapeutics2020

Caspase-1 inhibition prevents neuronal death by targeting the canonical inflammasome pathway of pyroptosis in a murine model of cerebral ischemia.

Jia Li, Jia-Huan Hao, Di Yao, Rong Li, Xue-Fei Li, Zhi-Yuan Yu, Xiang Luo, Xing-Hua Liu, Ming-Huan Wang, Wei Wang

Open access · goldAbstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
5.2field-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

58 citing papers in PubMed, 90 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

10 authors at 1 institution in 1 country.

Jia LiDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jia-Huan HaoDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Di YaoDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Rong LiDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xue-Fei LiDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zhi-Yuan YuDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xiang LuoDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xing-Hua LiuTrauma Center/Department of Emergency and Trauma Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ming-Huan WangDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.ORCID 0000-0003-2879-5741
Wei WangDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Tongji Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThe involvement of pyroptosis in ischemic stroke remains to be established. Therefore, we used the specific pyroptosis inhibitor Vx765 as an experimental intervention target in a murine model of stroke.

methodsA total of 564 C57BL/6 mice were subjected to photothrombotic procedures and treated via gavage with Vx765 at 1-hour post-ischemia. We subsequently assessed the expression of Gasdermin D (GSDMD), inflammasomes, caspase-1, and interleukin-1β (IL-1β) using immunofluorescence (IF) and Western blot (WB) analyses. We also examined ultrastructural changes of cortical neurons with transmission electron microscopy (TEM) and measured infarct volumes dynamically by magnetic resonance imaging (MRI). Moreover, we evaluated the neurologic deficits by modified neurological severity scores, the rotarod test, and Treadscan.

resultsElevated expression of GSDMD and GSDMD p30, the pore-forming subunit, was evident in the peri-ischemic region on days one and three post-ischemia. The neuronal plasma, nuclear, and mitochondrial membranes showed ultrastructural damage at day three post-stroke. Elevated expression of inflammasomes, caspase-1, and IL-1β was also present on days one and three post-injury. There were significant differences between Vx765-treated and vehicle groups in mean infarct volumes (14.36 vs 21.52 mm

conclusionsPyroptosis emerges as an important pathway for neuronal death in an acute ischemic stroke. Vx765, a low molecular weight drug that has proven safe in clinical epilepsy trials, has potential therapeutic value for cerebral ischemia by targeting the canonical inflammasome pathway of pyroptosis.

Indexed as

AnimalsBrain IschemiaCaspase 1Caspase InhibitorsCell DeathDipeptidesDrug Delivery SystemsInflammasomesMaleMiceMice, Inbred C57BLNeuronspara-AminobenzoatesPyroptosisbelnacasanCasp1 protein, mouseCaspase 1Caspase InhibitorsDipeptidesInflammasomespara-Aminobenzoatescerebral ischemic infarctsgasdermin DneuroprotectionpyroptosisVx765

Identifiers

PMID32343048
PMCPMC7415206
OpenAlexW3020566769

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.