Cepparulo, Pasquale (2017) IDENTIFICATION OF MICRORNAs REGULATING IONIC HOMEOSTASIS AS DIAGNOSTIC AND THERAPEUTIC TOOLS FOR CEREBRAL ISCHEMIA. [Tesi di dottorato]

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Ischemic stroke is a multifaced pathology that involves gene reprogramming. Among those genes whose expression is influenced by cerebral ischemia can be included the plasmamembrane protein sodium-calcium exchanger-1 (NCX1), whose activity is tightly related to stroke outcome. We have recently identified a microRNA (miR-103-1) able to selectively modulate NCX1 expression in brain during stroke and whose inhibition by anti-miR-103 causes brain damage reduction accompanied by NCX1 upregulation. Furthermore, it has been recently demonstrated that a short occlusion of an artery in a separate district of the body is able to protect the brain from a previous harmful ischemic insult: a phenomenon termed “remote ischemic postconditioning” (RIPO). Little is known about neural pathways and humoral mediators that are triggered by this neuroprotective approach. In this work we hypothesize that miRNAs released in biofluids within exosomes, small microvesicles of endosomal origin important in cell-to-cell communication, may serve as messengers from blood to CNS. To this aim, we performed a screening of rat miRNome, in order to identify miRNAs that are modulated in brain after stroke and RIPO treatment. Finally, in order to verify whether NCX is involved in RIPO mechanisms able to restore ionic homeostasis, we investigated whether NCX expression was modulated after RIPO through miR-103.

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