Natasha Irrera, Vincenzo Arcoraci, Federica Mannino, Giovanna Vermiglio, Giovanni Pallio, Letteria Minutoli, Gianluca Bagnato, Giuseppe Pio Anastasi, Emanuela Mazzon, Placido Bramanti, Francesco Squadrito, Domenica Altavilla, Alessandra Bitto
Abstract
Spinal cord injury (SCI) is a complex clinical and progressive condition characterized by neuronal loss, axonal destruction and demyelination. In the last few years, adenosine receptors have been studied as a target for many diseases, including neurodegenerative conditions. The aim of this study was to investigate the effects of an adenosine receptor agonist, PDRN, in an experimental model of SCI. Moreover, since adenosine receptors stimulation may also activate the Wnt pathway, we wanted to study PDRN effects on Wnt signaling following SCI. Spinal trauma was induced by extradural compression of spinal cord at T5-T8 level in C57BL6/J mice. Animals were randomly assigned to the following groups: Sham (n = 10), SCI (n = 14), SCI+PDRN (8 mg/kg/i.p.; n = 14), SCI+PDRN+DMPX (8 and 10 mg/kg/i.p., respectively; n = 14). DMPX was used as an adenosine receptor antagonist to evaluate whether adenosine receptor block might prevent PDRN effects. PDRN systemically administered 1 h following SCI, protected from tissue damage, demyelination, and reduced motor deficits evaluated after 10 days. PDRN also reduced the release of the pro-inflammatory cytokines TNF-α and IL-1β, reduced BAX expression and preserved Bcl-2. Furthermore, PDRN stimulated Wnt/β-catenin pathway and decreased apoptotic process 24 h following SCI, whereas DMPX administration prevented PDRN effects on Wnt/β-catenin signaling. These results confirm PDRN anti-inflammatory activity and demonstrate that a crosstalk between Wnt/β-catenin signaling is possible by adenosine receptors activation. Moreover, these data let us hypothesize that PDRN might promote neural repair through axonal regeneration and/or neurogenesis.
Pharmacology, Toxicology and Pharmaceutical Science
3
9%
Medicine and Dentistry
3
9%
Immunology and Microbiology
2
6%
Other
6
17%
Unknown
13
37%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 November 2022.
All research outputs
#16,833,528
of 24,752,377 outputs
Outputs from Frontiers in Pharmacology
#7,384
of 18,802 outputs
Outputs of similar age
#216,763
of 337,110 outputs
Outputs of similar age from Frontiers in Pharmacology
#147
of 399 outputs
Altmetric has tracked 24,752,377 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 18,802 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. This one has gotten more attention than average, scoring higher than 56% of its peers.
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We're also able to compare this research output to 399 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 61% of its contemporaries.
