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Article

A Synergistic Effect of Reactive Oxygen and Reactive Nitrogen Species in Plasma Activated Liquid Media Triggers Astrocyte Wound Healing

1
Institute of Nanotechnology, National Research Council of Italy (CNR-NANOTEC), c/o Department of Chemistry, University of Bari Aldo Moro, 70126 Bari, Italy
2
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy
3
Department of Chemistry, University of Bari Aldo Moro, 70126 Bari, Italy
4
Department of Biomedical Sciences and Human Oncology, Medical School, University of Bari Aldo Moro, 70124 Bari, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(9), 3343; https://doi.org/10.3390/ijms21093343
Received: 29 March 2020 / Revised: 24 April 2020 / Accepted: 6 May 2020 / Published: 8 May 2020
(This article belongs to the Special Issue Cell Adhesion and Migration in Health and Diseases)
Astrocyte proliferation and migration toward injured Central Nervous System (CNS) areas are key features of astrogliosis and glial scar formation. Even though it is known that intracellular and environmental Reactive Oxygen and Nitrogen Species (RONS) affect astrocyte behaviour in physiological and pathophysiological conditions, their effects on the migration and growth of astrocytes are still unclear. Plasma-technologies are emerging in medicine as a tool to generate RONS for treating cells directly or through Plasma Activated Liquid Media (PALM). In this paper, we show for the first time how the use of PALM can modulate both astrocyte growth and migration as a function of active species produced by plasma in liquids. Our results show that PALM, generated by means of cold atmospheric pressure plasmas fed with N2, air or O2, can modulate astrocyte behaviour depending on the content of hydrogen peroxide and nitrite in the liquid. In particular, H2O2 enriched PALM induced a negative effect on cell growth associated with the mild wound healing improvement of primary astrocytes, in a scratch assay. Nitrite enriched PALM induced a selective effect on the wound healing without affecting cell growth. PALM containing a more balanced level of H2O2 and NO2 were able to affect cell growth, as well as significantly ameliorate wound healing. None of the PALM investigated induced upregulation of the gliotic inflammatory marker glial fibrillary acidic protein (GFAP), or of the astrocyte markers Aquaporin-4 (AQP4) and Connexin-43 (Cx-43) analysed by Western blot. Finally, immunofluorescence analysis revealed the presence of NO2- able to induce elongated protrusions at the front end of wounded astrocytes in the direction of cell migration. With our study we believe to have shown that PALM offer a novel tool to modulate astrocyte behaviour and that they are promising candidates for controlling astrogliosis in the case of CNS injuries. View Full-Text
Keywords: astrocytes; wound healing; plasma activated medium; oxidative stress astrocytes; wound healing; plasma activated medium; oxidative stress
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MDPI and ACS Style

Sardella, E.; Mola, M.G.; Gristina, R.; Piccione, M.; Veronico, V.; De Bellis, M.; Cibelli, A.; Buttiglione, M.; Armenise, V.; Favia, P.; Nicchia, G.P. A Synergistic Effect of Reactive Oxygen and Reactive Nitrogen Species in Plasma Activated Liquid Media Triggers Astrocyte Wound Healing. Int. J. Mol. Sci. 2020, 21, 3343. https://doi.org/10.3390/ijms21093343

AMA Style

Sardella E, Mola MG, Gristina R, Piccione M, Veronico V, De Bellis M, Cibelli A, Buttiglione M, Armenise V, Favia P, Nicchia GP. A Synergistic Effect of Reactive Oxygen and Reactive Nitrogen Species in Plasma Activated Liquid Media Triggers Astrocyte Wound Healing. International Journal of Molecular Sciences. 2020; 21(9):3343. https://doi.org/10.3390/ijms21093343

Chicago/Turabian Style

Sardella, Eloisa, Maria G. Mola, Roberto Gristina, Monica Piccione, Valeria Veronico, Manuela De Bellis, Antonio Cibelli, Maura Buttiglione, Vincenza Armenise, Pietro Favia, and Grazia P. Nicchia 2020. "A Synergistic Effect of Reactive Oxygen and Reactive Nitrogen Species in Plasma Activated Liquid Media Triggers Astrocyte Wound Healing" International Journal of Molecular Sciences 21, no. 9: 3343. https://doi.org/10.3390/ijms21093343

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