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L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction
Background: Spinal cord injury (SCI) elicits robust neuroinflammation that eventually exacerbates the initial damage to the spinal cord. L-arginine is critical for the responsiveness of T cells, which are important contributors to neuroinflammation after SCI. Furthermore, L-arginine is the substrate...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869469/ https://www.ncbi.nlm.nih.gov/pubmed/35203413 http://dx.doi.org/10.3390/biomedicines10020205 |
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author | Erens, Céline Van Broeckhoven, Jana Hoeks, Cindy Schabbauer, Gernot Cheng, Paul N. Chen, Li Hellings, Niels Broux, Bieke Lemmens, Stefanie Hendrix, Sven |
author_facet | Erens, Céline Van Broeckhoven, Jana Hoeks, Cindy Schabbauer, Gernot Cheng, Paul N. Chen, Li Hellings, Niels Broux, Bieke Lemmens, Stefanie Hendrix, Sven |
author_sort | Erens, Céline |
collection | PubMed |
description | Background: Spinal cord injury (SCI) elicits robust neuroinflammation that eventually exacerbates the initial damage to the spinal cord. L-arginine is critical for the responsiveness of T cells, which are important contributors to neuroinflammation after SCI. Furthermore, L-arginine is the substrate for nitric oxide (NO) production, which is a known inducer of secondary damage. Methods: To accomplish systemic L-arginine depletion, repetitive injections of recombinant arginase-1 (rArg-I) were performed. Functional recovery and histopathological parameters were analyzed. Splenic immune responses were evaluated by flow cytometry. Pro-inflammatory gene expression and nitrite concentrations were measured. Results: We show for the first time that systemic L-arginine depletion improves locomotor recovery. Flow cytometry and immunohistological analysis showed that intraspinal T-cell infiltration was reduced by 65%, and peripheral numbers of Th1 and Th17 cells were suppressed. Moreover, rArg-I treatment reduced the intraspinal NO production by 40%. Histopathological analyses revealed a 37% and 36% decrease in the number of apoptotic neurons and neuron-macrophage/microglia contacts in the spinal cord, respectively. Conclusions: Targeting detrimental T-cell responses and NO-production via rArg-I led to a reduced neuronal cell death and an improved functional recovery. These findings indicate that L-arginine depletion holds promise as a therapeutic strategy after SCI. |
format | Online Article Text |
id | pubmed-8869469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88694692022-02-25 L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction Erens, Céline Van Broeckhoven, Jana Hoeks, Cindy Schabbauer, Gernot Cheng, Paul N. Chen, Li Hellings, Niels Broux, Bieke Lemmens, Stefanie Hendrix, Sven Biomedicines Article Background: Spinal cord injury (SCI) elicits robust neuroinflammation that eventually exacerbates the initial damage to the spinal cord. L-arginine is critical for the responsiveness of T cells, which are important contributors to neuroinflammation after SCI. Furthermore, L-arginine is the substrate for nitric oxide (NO) production, which is a known inducer of secondary damage. Methods: To accomplish systemic L-arginine depletion, repetitive injections of recombinant arginase-1 (rArg-I) were performed. Functional recovery and histopathological parameters were analyzed. Splenic immune responses were evaluated by flow cytometry. Pro-inflammatory gene expression and nitrite concentrations were measured. Results: We show for the first time that systemic L-arginine depletion improves locomotor recovery. Flow cytometry and immunohistological analysis showed that intraspinal T-cell infiltration was reduced by 65%, and peripheral numbers of Th1 and Th17 cells were suppressed. Moreover, rArg-I treatment reduced the intraspinal NO production by 40%. Histopathological analyses revealed a 37% and 36% decrease in the number of apoptotic neurons and neuron-macrophage/microglia contacts in the spinal cord, respectively. Conclusions: Targeting detrimental T-cell responses and NO-production via rArg-I led to a reduced neuronal cell death and an improved functional recovery. These findings indicate that L-arginine depletion holds promise as a therapeutic strategy after SCI. MDPI 2022-01-18 /pmc/articles/PMC8869469/ /pubmed/35203413 http://dx.doi.org/10.3390/biomedicines10020205 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Erens, Céline Van Broeckhoven, Jana Hoeks, Cindy Schabbauer, Gernot Cheng, Paul N. Chen, Li Hellings, Niels Broux, Bieke Lemmens, Stefanie Hendrix, Sven L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction |
title | L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction |
title_full | L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction |
title_fullStr | L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction |
title_full_unstemmed | L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction |
title_short | L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction |
title_sort | l-arginine depletion improves spinal cord injury via immunomodulation and nitric oxide reduction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869469/ https://www.ncbi.nlm.nih.gov/pubmed/35203413 http://dx.doi.org/10.3390/biomedicines10020205 |
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