L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction.
CNS trauma
T cells
arginase-1
neuroinflammation
nitric oxide
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
18 Jan 2022
18 Jan 2022
Historique:
received:
01
10
2021
revised:
03
12
2021
accepted:
12
01
2022
entrez:
25
2
2022
pubmed:
26
2
2022
medline:
26
2
2022
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 35203413
pii: biomedicines10020205
doi: 10.3390/biomedicines10020205
pmc: PMC8869469
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Research Foundation - Flanders
ID : G067715N
Organisme : Research Foundation - Flanders
ID : G091518N
Organisme : Research Foundation - Flanders
ID : G0C2120N
Organisme : Stichting MS Research
ID : N.A.
Organisme : MS International Federation (MSIF) and MoveS
ID : N.A.
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