Early Administration of l-Arginine in Experimental Acute Spinal Cord Injury Impairs Long-Term Motor Function Recovery

Esquivel-Aguilar, Abdieel; Castañeda‐Hernández, Gilberto; Martínez-Cruz, Angelina; Franco-Bourland, Rebecca E.; Madrazo, Ignacio; Guı́zar-Sahagún, Gabriel

doi:10.1097/ta.0b013e3181e3e5c1

Cited by 5 publications

(5 citation statements)

References 25 publications

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“…Some studies have shown that arginase is very important in providing ornithine as a precursor to the synthesis of polyamines, which are involved in the control of DNA, RNA, and protein synthesis during cell growth, differentiation, and development (Fozard et al, 1980;Pegg et al, 1982;Hougaard, 1992) and are important in embryonic development (Kusunoki and Yasumasu, 1978) . Some studies reported that hyperargininemic patients have as their primary symptoms delayed development associated with progressive spastic paraparesis (Scaglia and Lee, 2006;Esquivel-Aguilar et al, 2011). The Arg doses chosen in this study are consistent with those levels achieved in plasma and cerebrum of hyperarginemic patients which ranges around of 1.3 mM and 0.3 nmol/kg, respectively (Buchmann et al, 1996).…”

Section: Discussionsupporting

confidence: 85%

“…Some studies reported that hyperargininemic patients have as their primary symptoms delayed development associated with progressive spastic paraparesis (Scaglia and Lee, 2006; Esquivel‐Aguilar et al, 2011). The Arg doses chosen in this study are consistent with those levels achieved in plasma and cerebrum of hyperarginemic patients which ranges around of 1.3 mM and 0.3 nmol/kg, respectively (Buchmann et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

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Arginine exposure alters ectonucleotidase activities and morphology of zebrafish larvae (Danio rerio)

Capiotti

Fazenda

Nazario

et al. 2012

Intl J of Devlp Neuroscience

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Hyperargininemia is an inborn error of metabolism (IEM) characterized by tissue accumulation of arginine (Arg). Mental retardation and other neurological features are common symptoms in hyperargininemic patients. Considering purinergic signaling has a crucial role from the early stages of development and underlying mechanisms of this disease are poorly established, we investigated the effect of Arg administration on locomotor activity, morphological alterations, and extracellular nucleotide hydrolysis in larvae and adult zebrafish. We showed that 0.1 mM Arg was unable to promote changes in locomotor activity. In addition, 7-day-post-fertilization (dpf) larvae treated with Arg demonstrated a decreased body size. Arg exposure (0.1 mM) promoted an increase in ATP, ADP, and AMP hydrolysis when compared to control group. These findings demonstrated that Arg might affect morphological parameters and ectonucleotidase activities in zebrafish larvae, suggesting that purinergic system is a target for neurotoxic effects induced by Arg.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Arginine exposure alters ectonucleotidase activities and morphology of zebrafish larvae (Danio rerio)

Capiotti

Fazenda

Nazario

et al. 2012

Intl J of Devlp Neuroscience

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“…Only a few studies so far have investigated the impact of L-arginine depletion in neuroinflammatory pathologies [ 26 , 50 ]. Moreover, limited investigation has been conducted on the effects of L-arginine administration on SCI outcome, showing contradictory results [ 29 , 30 , 31 , 32 ]. Tuncer et al and Yüceer and colleagues reported a beneficial effect of L-arginine administration [ 30 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, Esquivel-Aguilar et al found a detrimental impact on functional recovery 8 weeks post-injury after 300 mg/kg L-arginine administration and contusion SCI. Moreover, Savas et al showed an increase of detrimental NO production and NO-mediated cell damage 2 h after ischemia-induced SCI and 100 mg/kg L-arginine administration [ 29 , 31 ]. These conflicting findings might result from differences in the applied L-arginine concentration, the chosen SCI model, and time point for examining the tissue integrity and functional recovery.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is unclear whether it plays a protective or degenerative role [ 27 , 28 ]. Supplementation of L-arginine after SCI resulted in beneficial effects in some studies and detrimental effects in others [ 29 , 30 , 31 , 32 ]. To date, the role of L-arginine in the traumatic inflammatory processes after SCI, still remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

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L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction

et al. 2022

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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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Decreased GFAP Expression and Improved Functional Recovery in Contused Spinal Cord of Rats Following Valproic Acid Therapy

et al. 2014

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Many studies have illustrated that much of the post-traumatic degeneration of the spinal cord cells is caused by the secondary mechanism. The aim of this study is to evaluate the effect of the anti-inflammatory property of valproic acid (VPA) on injured spinal cords (SC). The rats with the contused SC received intraperitoneal single injection of VPA (150, 200, 300, 400 or 500 mg/kg) at 2, 6, 12 and 24 h post-injury. Basso-Beattie-Bresnahan (BBB) test and H-reflex evaluated the functional outcome for 12 weeks. The SC were investigated 3 months post-injury using morphometry and glial fibrillary acid protein (GFAP) expression. Reduction in cavitation, H/M ratio, BBB scores and GFAP expression in the treatment groups were significantly more than that of the untreated one (P < 0.05). The optimal improvement in the condition of the contused rats was in the ones treated at the acute phase of injury with 300 mg/kg of VPA at 12 h post-injury, they had the highest increase in BBB score and decrease in astrogliosis and axonal loss. We conclude that treating the contused rats with 300 mg/kg of VPA at 12 h post-injury improves the functional outcome and reduces the traumatized SC gliosis.

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Early Administration of l-Arginine in Experimental Acute Spinal Cord Injury Impairs Long-Term Motor Function Recovery

Cited by 5 publications

References 25 publications

Arginine exposure alters ectonucleotidase activities and morphology of zebrafish larvae (Danio rerio)

Arginine exposure alters ectonucleotidase activities and morphology of zebrafish larvae (Danio rerio)

L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction

Decreased GFAP Expression and Improved Functional Recovery in Contused Spinal Cord of Rats Following Valproic Acid Therapy

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