Systemic administration of blood-derived exosomes induced by remote ischemic post-conditioning, by delivering a specific cluster of miRNAs, ameliorates ischemic damage and neurological function.

Autor:	Cuomo O; Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples Federico II, Naples, Italy., Anzilotti S; Department of Science and Technology, University of Sannio, Benevento, Italy., Brancaccio P; Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples Federico II, Naples, Italy., Cepparulo P; Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples Federico II, Naples, Italy., Lombardi G; Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples Federico II, Naples, Italy., Viscardi V; Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples Federico II, Naples, Italy.; International School of Advanced Studies, University of Camerino, Camerino, Italy., Vinciguerra A; Department of Biomedical Sciences and Public Healty, University 'Politecnica delle Marche', Ancona, Italy., Annunziato L; IRCCS SYNLAB SDN S.p.A., Naples, Italy., Pignataro G; Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples Federico II, Naples, Italy.
Jazyk:	angličtina
Zdroj:	Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism [J Cereb Blood Flow Metab] 2024 Dec; Vol. 44 (12), pp. 1459-1471. Date of Electronic Publication: 2024 Aug 11.
DOI:	10.1177/0271678X241270284
Abstrakt:	MicroRNAs, contained in exosomes or freely circulating in the plasma, might play a pivotal role in the infarct-sparing effect exerted by r emote limb ischemic postconditioning (RLIP). The aims of the present study were: (1) To evaluate the effect of pure exosomes isolated from plasma of animals subjected to RLIP systemically administered to ischemic rats; (2) To finely dissect exosomes content in terms of miRNAs; (3) To select those regulatory miRNAs specifically expressed in protective exosomes and to identify molecular pathways involved in their neurobeneficial effects. Circulating exosomes were isolated from blood of animals exposed to RLIP and administered to animals exposed to tMCAO by intracerebroventricular, intraperitoneal or intranasal routes. Exosomal miRNA signature was evaluated by microarray and FISH analysis. Plasmatic exosomes isolated from plasma of RLIP rats attenuated cerebral ischemia reperfusion injury and improved neurological functions until 3 days after ischemia induction. Interestingly, miR-702-3p and miR-423-5p seem to be mainly involved in exosome protective action by modulating NOD1 and NLRP3, two key triggers of neuroinflammation and neuronal death. Collectively, the results of the present work demonstrated that plasma-released exosomes after RLIP may transfer a neuroprotective signal to the brain of ischemic animals, thus representing a potentially translatable therapeutic strategy in stroke. Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Databáze:	MEDLINE
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