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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...

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Autores principales: Erens, Céline, Van Broeckhoven, Jana, Hoeks, Cindy, Schabbauer, Gernot, Cheng, Paul N., Chen, Li, Hellings, Niels, Broux, Bieke, Lemmens, Stefanie, Hendrix, Sven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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