Evidence map›Paper›PMID 40507777›Full record

ArticleInternational journal of molecular sciences2025

Inhibition of Ferroptosis Attenuates Neuron Damage and Improves Cognitive Impairment in Mice Surviving Severe Hypothermia.

Wei-Xuan Li, Xue-Tong Dong, Fu Zhang, Jun-Yan Wang, Chao-Long Lu, Zhao-Qi Zhou, Jia-Yi Gu, Song-Jun Wang

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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.

Wei-Xuan LiUndergraduate Program of College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China.
Xue-Tong DongHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China.
Fu ZhangForensic Pathology Laboratory, Guangdong Public Security Department, No. 97 Huanghua Road, Guangzhou 510050, China.
Jun-Yan WangHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China.
Chao-Long LuHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China.
Zhao-Qi ZhouUndergraduate Program of College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China.
Jia-Yi GuUndergraduate Program of College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China.
Song-Jun WangHebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China.

Funding

Key Program of National Natural Science Foundation of China 82130055Major Program of National Natural Science Foundation of China 82293651Natural Science Foundation of Hebei Province H2024206002Open Project of the Key Laboratory of Forensic Pathology of the Ministry of Public Security GAFYBL202303Science and Technology Research Project of Colleges and Universities in Hebei Province ZD2022132Shanghai Key Laboratory of Forensic Medicine and Key Laboratory of Forensic Science, Ministry of Justice KF202404
6 · The paper itself

Abstract

Survivors of severe hypothermia frequently exhibit cognitive impairments. However, the underlying mechanisms remain inadequately understood. In order to reveal the scientific problem of cognitive dysfunction caused by severe hypothermia, providing an experimental basis for clinical treatment, this study utilized animal models and combined cognitive behavioral, morphological, and molecular biological experiments. The results showed that severe hypothermia leads to an accumulation of iron ions in the cerebral cortex tissue exceeding 70%, while increased Acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) expression enhances sensitivity to ferroptosis. This process results in a nearly 50% decrease in glutathione (GSH) expression and over 50% degradation of glutathione peroxidase 4 (GPX4), leading to GPX4 deactivation and increased lipid peroxidation, which in turn nearly doubles the levels of oxidative products such as MDA and 4NHE. Notably, ferroptosis inhibition using Ferrostatin-1 (Fer-1) effectively mitigates the degenerative death of cerebral cortical neurons induced by severe hypothermia, significantly improving the associated cognitive deficits. These findings suggest that severe hypothermia may induce ferroptosis in cortical neurons through the Nrf2/SLC7A11/GSH/GPX4 signaling axis. Targeted inhibition of ferroptosis has the potential to be a promising therapeutic direction for the prevention and treatment of cognitive impairment caused by severe hypothermia.

Indexed as

Cognitive DysfunctionCyclohexylaminesFerroptosisHypothermiaNeuronsPhenylenediaminesAmino Acid Transport System y+AnimalsCerebral CortexCoenzyme A LigasesDisease Models, AnimalGlutathioneIronLipid PeroxidationMaleMiceAcsl4 protein, mouseAmino Acid Transport System y+Coenzyme A LigasesCyclohexylaminesferrostatin-1Glutathioneglutathione peroxidase 4, mouseIronNfe2l2 protein, mouseNF-E2-Related Factor 2PhenylenediaminesPhospholipid Hydroperoxide Glutathione PeroxidaseSlc7a11 protein, mousecerebral corticalcognitive impairmentferroptosishypothermianerve cells

Identifiers

PMID40507777
PMCPMC12154239

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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.