Propofol and α2-Agonists Attenuate Microglia Activation and Restore Mitochondrial Function in an In Vitro Model of Microglia Hypoxia/Reoxygenation
Lucia Longhitano,
Alfio Distefano,
Paolo Murabito,
Marinella Astuto,
Anna Nicolosi,
Giovanni Buscema,
Filippo Sanfilippo,
Giuseppe Lazzarino,
Angela Maria Amorini,
Andrea Bruni,
Eugenio Garofalo,
Daniele Tibullo,
Giovanni Li Volti
Affiliations
Lucia Longhitano
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95125 Catania, Italy
Alfio Distefano
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95125 Catania, Italy
Paolo Murabito
Unità Operativa Complessa Anestesia e Rianimazione 2, Azienda Universitaria “Policlinico G. Rodolico” Via S. Sofia 97, 95125 Catania, Italy
Marinella Astuto
Unità Operativa Complessa Anestesia e Rianimazione 2, Azienda Universitaria “Policlinico G. Rodolico” Via S. Sofia 97, 95125 Catania, Italy
Anna Nicolosi
Azienda Ospedaliera “Cannizzaro”, Via Messina 628, 95126 Catania, Italy
Giovanni Buscema
Unità Operativa Complessa Anestesia e Rianimazione 2, Azienda Universitaria “Policlinico G. Rodolico” Via S. Sofia 97, 95125 Catania, Italy
Filippo Sanfilippo
Unità Operativa Complessa Anestesia e Rianimazione 2, Azienda Universitaria “Policlinico G. Rodolico” Via S. Sofia 97, 95125 Catania, Italy
Giuseppe Lazzarino
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95125 Catania, Italy
Angela Maria Amorini
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95125 Catania, Italy
Andrea Bruni
Anesthesia and Intesive Care Unit, Department of Medical and Surgical Sciences, University Hospital Mater Domini, Magna Grecia University, 88100 Catanzaro, Italy
Eugenio Garofalo
Anesthesia and Intesive Care Unit, Department of Medical and Surgical Sciences, University Hospital Mater Domini, Magna Grecia University, 88100 Catanzaro, Italy
Daniele Tibullo
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95125 Catania, Italy
Giovanni Li Volti
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95125 Catania, Italy
Cerebrovascular ischemia is a common clinical disease encompassing a series of complex pathophysiological processes in which oxidative stress plays a major role. The present study aimed to evaluate the effects of Dexmedetomidine, Clonidine, and Propofol in a model of hypoxia/reoxygenation injury. Microglial cells were exposed to 1%hypoxia for 3 h and reoxygenated for 3 h, and oxidative stress was measured by ROS formation and the expression of inflammatory process genes. Mitochondrial dysfunction was assessed by membrane potential maintenance and the levels of various metabolites involved in energetic metabolism. The results showed that Propofol and α2-agonists attenuate the formation of ROS during hypoxia and after reoxygenation. Furthermore, the α2-agonists treatment restored membrane potential to values comparable to the normoxic control and were both more effective than Propofol. At the same time, Propofol, but not α2-agonists, reduces proliferation (Untreated Hypoxia = 1.16 ± 0.2, Untreated 3 h Reoxygenation = 1.28 ± 0.01 vs. Propofol hypoxia = 1.01 ± 0.01 vs. Propofol 3 h Reoxygenation = 1.12 ± 0.03) and microglial migration. Interestingly, all of the treatments reduced inflammatory gene and protein expressions and restored energy metabolism following hypoxia/reoxygenation (ATP content in hypoxia/reoxygenation 3 h: Untreated = 3.11 ± 0.8 vs. Propofol = 7.03 ± 0.4 vs. Dexmedetomidine = 5.44 ± 0.8 vs. Clonidine = 7.70 ± 0.1), showing that the drugs resulted in a different neuroprotective profile. In conclusion, our results may provide clinically relevant insights for neuroprotective strategies in intensive care units.
