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http://hdl.handle.net/1942/36695
Title: | L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction | Authors: | ERENS, Celine VAN BROECKHOVEN, Jana HOEKS, Cindy Schabbauer, Gernot Cheng, Paul Chen, Li HELLINGS, Niels BROUX, Bieke LEMMENS, Stefanie HENDRIX, Sven |
Issue Date: | 2022 | Publisher: | MDPI | Source: | Biomedicines, 10 (2) (Art N° 205) | Abstract: | Abstract: 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 arginase1 (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. | Keywords: | arginase-1;CNS trauma;neuroinflammation;nitric oxide;T cells | Document URI: | http://hdl.handle.net/1942/36695 | e-ISSN: | 2227-9059 | DOI: | 10.3390/biomedicines10020205 | ISI #: | 000770839900001 | Rights: | Copyright: © 2022 by the authors. 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/). | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
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biomedicines-10-00205-v2-final.pdf | Published version | 3.67 MB | Adobe PDF | View/Open |
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