Zinc regulates microglial polarization and inflammation through IKBα after spinal cord injury and promotes neuronal repair and motor function recovery in mice

IntroductionSpinal cord injury (SCI) leads to severe inflammation and neuronal damage, resulting in permanent loss of motor and sensory functions. Zinc ions have shown potential in modulating inflammation and cellular survival, making them a promising therapeutic approach for SCI. This study investi...

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Main Authors: Daoyong Li, Mingyu Bai, Zhanpeng Guo, Yang Cui, Xifan Mei, He Tian, Zhaoliang Shen
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1510372/full
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author Daoyong Li
Daoyong Li
Mingyu Bai
Mingyu Bai
Zhanpeng Guo
Yang Cui
Yang Cui
Xifan Mei
Xifan Mei
He Tian
He Tian
Zhaoliang Shen
author_facet Daoyong Li
Daoyong Li
Mingyu Bai
Mingyu Bai
Zhanpeng Guo
Yang Cui
Yang Cui
Xifan Mei
Xifan Mei
He Tian
He Tian
Zhaoliang Shen
author_sort Daoyong Li
collection DOAJ
description IntroductionSpinal cord injury (SCI) leads to severe inflammation and neuronal damage, resulting in permanent loss of motor and sensory functions. Zinc ions have shown potential in modulating inflammation and cellular survival, making them a promising therapeutic approach for SCI. This study investigates the mechanisms of zinc ion treatment in SCI, focusing on its effects on inflammation.MethodsWe used transcriptomic analysis to identify key pathways and genes involved in the inflammatory response in a mouse model of SCI. In vitro studies assessed the impact of zinc ions on inflammation, cell polarization, and apoptosis. IKBα expression was evaluated as a potential target of zinc ions, both in cultured cells and in vivo.ResultsTranscriptomic analysis revealed that zinc ions modulate inflammatory pathways through IKBα, which inhibits NF-κB activity. In vitro, zinc treatment upregulated IKBα expression, reducing inflammation, polarization, and apoptosis. These results were confirmed in the SCI mouse model, where zinc ions also reduced inflammation and cell death.DiscussionOur findings highlight a novel mechanism by which zinc ions regulate inflammation in SCI by upregulating IKBα and inhibiting NF-κB activation. This suggests potential therapeutic applications of zinc ions in SCI and other inflammatory conditions, warranting further investigation into their clinical benefits.
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publishDate 2025-01-01
publisher Frontiers Media S.A.
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spelling doaj-art-bdf19e4ff42e4f5fb00d8c5c33055a232025-01-29T05:21:14ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011610.3389/fphar.2025.15103721510372Zinc regulates microglial polarization and inflammation through IKBα after spinal cord injury and promotes neuronal repair and motor function recovery in miceDaoyong Li0Daoyong Li1Mingyu Bai2Mingyu Bai3Zhanpeng Guo4Yang Cui5Yang Cui6Xifan Mei7Xifan Mei8He Tian9He Tian10Zhaoliang Shen11The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou City, Liaoning, ChinaKey Laboratory of Liaoning Medical Organization Engineering, Jinzhou, Liaoning, ChinaThe Third Affiliated Hospital of Jinzhou Medical University, Jinzhou City, Liaoning, ChinaKey Laboratory of Liaoning Medical Organization Engineering, Jinzhou, Liaoning, ChinaKey Laboratory of Liaoning Medical Organization Engineering, Jinzhou, Liaoning, ChinaThe Third Affiliated Hospital of Jinzhou Medical University, Jinzhou City, Liaoning, ChinaKey Laboratory of Liaoning Medical Organization Engineering, Jinzhou, Liaoning, ChinaThe Third Affiliated Hospital of Jinzhou Medical University, Jinzhou City, Liaoning, ChinaKey Laboratory of Liaoning Medical Organization Engineering, Jinzhou, Liaoning, ChinaKey Laboratory of Liaoning Medical Organization Engineering, Jinzhou, Liaoning, ChinaSchool of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning, ChinaThe Third Affiliated Hospital of Jinzhou Medical University, Jinzhou City, Liaoning, ChinaIntroductionSpinal cord injury (SCI) leads to severe inflammation and neuronal damage, resulting in permanent loss of motor and sensory functions. Zinc ions have shown potential in modulating inflammation and cellular survival, making them a promising therapeutic approach for SCI. This study investigates the mechanisms of zinc ion treatment in SCI, focusing on its effects on inflammation.MethodsWe used transcriptomic analysis to identify key pathways and genes involved in the inflammatory response in a mouse model of SCI. In vitro studies assessed the impact of zinc ions on inflammation, cell polarization, and apoptosis. IKBα expression was evaluated as a potential target of zinc ions, both in cultured cells and in vivo.ResultsTranscriptomic analysis revealed that zinc ions modulate inflammatory pathways through IKBα, which inhibits NF-κB activity. In vitro, zinc treatment upregulated IKBα expression, reducing inflammation, polarization, and apoptosis. These results were confirmed in the SCI mouse model, where zinc ions also reduced inflammation and cell death.DiscussionOur findings highlight a novel mechanism by which zinc ions regulate inflammation in SCI by upregulating IKBα and inhibiting NF-κB activation. This suggests potential therapeutic applications of zinc ions in SCI and other inflammatory conditions, warranting further investigation into their clinical benefits.https://www.frontiersin.org/articles/10.3389/fphar.2025.1510372/fullspinal cord injuryzincmicroglial polarizationinflammatory responsefunctional recovery
spellingShingle Daoyong Li
Daoyong Li
Mingyu Bai
Mingyu Bai
Zhanpeng Guo
Yang Cui
Yang Cui
Xifan Mei
Xifan Mei
He Tian
He Tian
Zhaoliang Shen
Zinc regulates microglial polarization and inflammation through IKBα after spinal cord injury and promotes neuronal repair and motor function recovery in mice
Frontiers in Pharmacology
spinal cord injury
zinc
microglial polarization
inflammatory response
functional recovery
title Zinc regulates microglial polarization and inflammation through IKBα after spinal cord injury and promotes neuronal repair and motor function recovery in mice
title_full Zinc regulates microglial polarization and inflammation through IKBα after spinal cord injury and promotes neuronal repair and motor function recovery in mice
title_fullStr Zinc regulates microglial polarization and inflammation through IKBα after spinal cord injury and promotes neuronal repair and motor function recovery in mice
title_full_unstemmed Zinc regulates microglial polarization and inflammation through IKBα after spinal cord injury and promotes neuronal repair and motor function recovery in mice
title_short Zinc regulates microglial polarization and inflammation through IKBα after spinal cord injury and promotes neuronal repair and motor function recovery in mice
title_sort zinc regulates microglial polarization and inflammation through ikbα after spinal cord injury and promotes neuronal repair and motor function recovery in mice
topic spinal cord injury
zinc
microglial polarization
inflammatory response
functional recovery
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1510372/full
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