Zinc deficiency impairs axonal regeneration and functional recovery after spinal cord injury by modulating macrophage polarization via NF-κB pathway Article Swipe
Ken Kijima
,
Gentaro Ono
,
Kazu Kobayakawa
,
Hirokazu Saiwai
,
Masamitsu Hara
,
Shingo Yoshizaki
,
Kazuya Yokota
,
Takeyuki Saito
,
Tetsuya Tamaru
,
Hirotaka Iura
,
Yohei Haruta
,
Kazuki Kitade
,
Takeshi Utsunomiya
,
Daijiro Konno
,
V. Reggie Edgerton
,
Charles Y. Liu
,
Hiroaki Sakai
,
Takeshi Maeda
,
Kenichi Kawaguchi
,
Yoshihiro Matsumoto
,
Seiji Okada
,
Yasuharu Nakashima
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2023.1290100
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2023.1290100
Background Spinal cord injury (SCI) is a devastating disease that results in permanent paralysis. Currently, there is no effective treatment for SCI, and it is important to identify factors that can provide therapeutic intervention during the course of the disease. Zinc, an essential trace element, has attracted attention as a regulator of inflammatory responses. In this study, we investigated the effect of zinc status on the SCI pathology and whether or not zinc could be a potential therapeutic target. Methods We created experimental mouse models with three different serum zinc concentration by changing the zinc content of the diet. After inducing contusion injury to the spinal cord of three mouse models, we assessed inflammation, apoptosis, demyelination, axonal regeneration, and the number of nuclear translocations of NF-κB in macrophages by using qPCR and immunostaining. In addition, macrophages in the injured spinal cord of these mouse models were isolated by flow cytometry, and their intracellular zinc concentration level and gene expression were examined. Functional recovery was assessed using the open field motor score, a foot print analysis, and a grid walk test. Statistical analysis was performed using Wilcoxon rank-sum test and ANOVA with the Tukey-Kramer test. Results In macrophages after SCI, zinc deficiency promoted nuclear translocation of NF-κB, polarization to pro-inflammatory like phenotype and expression of pro-inflammatory cytokines. The inflammatory response exacerbated by zinc deficiency led to worsening motor function by inducing more apoptosis of oligodendrocytes and demyelination and inhibiting axonal regeneration in the lesion site compared to the normal zinc condition. Furthermore, zinc supplementation after SCI attenuated these zinc-deficiency-induced series of responses and improved motor function. Conclusion We demonstrated that zinc affected axonal regeneration and motor functional recovery after SCI by negatively regulating NF-κB activity and the subsequent inflammatory response in macrophages. Our findings suggest that zinc supplementation after SCI may be a novel therapeutic strategy for SCI.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2023.1290100
- https://www.frontiersin.org/articles/10.3389/fimmu.2023.1290100/pdf?isPublishedV2=False
- OA Status
- gold
- Cited By
- 10
- References
- 61
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4388524259
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4388524259Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fimmu.2023.1290100Digital Object Identifier
- Title
-
Zinc deficiency impairs axonal regeneration and functional recovery after spinal cord injury by modulating macrophage polarization via NF-κB pathwayWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-11-08Full publication date if available
- Authors
-
Ken Kijima, Gentaro Ono, Kazu Kobayakawa, Hirokazu Saiwai, Masamitsu Hara, Shingo Yoshizaki, Kazuya Yokota, Takeyuki Saito, Tetsuya Tamaru, Hirotaka Iura, Yohei Haruta, Kazuki Kitade, Takeshi Utsunomiya, Daijiro Konno, V. Reggie Edgerton, Charles Y. Liu, Hiroaki Sakai, Takeshi Maeda, Kenichi Kawaguchi, Yoshihiro Matsumoto, Seiji Okada, Yasuharu NakashimaList of authors in order
- Landing page
-
https://doi.org/10.3389/fimmu.2023.1290100Publisher landing page
- PDF URL
-
https://www.frontiersin.org/articles/10.3389/fimmu.2023.1290100/pdf?isPublishedV2=FalseDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.frontiersin.org/articles/10.3389/fimmu.2023.1290100/pdf?isPublishedV2=FalseDirect OA link when available
- Concepts
-
Spinal cord injury, Medicine, Pathology, Inflammation, Proinflammatory cytokine, Spinal cord, Immunology, PsychiatryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
10Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 6, 2024: 4Per-year citation counts (last 5 years)
- References (count)
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61Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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