Remote damage is a secondary phenomenon that usually occurs after a primary brain damage in regions that are distant, yet functionally connected, and that is critical for determining the outcomes of several CNS pathologies, including traumatic brain and spinal cord injuries. The understanding of remote damage-associated mechanisms has been mostly achieved in several models of focal brain injury such as the hemicerebellectomy (HCb) experimental paradigm, which helped to identify the involvement of many key players, such as inflammation, oxidative stress, apoptosis and autophagy. Currently, few interventions have been shown to successfully limit the progression of secondary damage events and there is still an unmet need for new therapeutic options. Given the emergence of the novel concept of resolution of inflammation, mediated by the newly identified ω3-derived specialized pro-resolving lipid mediators, such as resolvins, we reported a reduced ability of HCb-injured animals to produce resolvin D1 (RvD1) and an increased expression of its target receptor ALX/FPR2 in remote brain regions. The in vivo administration of RvD1 promoted functional recovery and neuroprotection by reducing the activation of Iba-1+ microglia and GFAP+ astrocytes as well as by impairing inflammatory-induced neuronal cell death in remote regions. These effects were counteracted by intracerebroventricular neutralization of ALX/FPR2, whose activation by RvD1 also down-regulated miR-146b and miR-219a-1-dependent inflammatory markers. In conclusion, we propose that innovative therapies based on RvD1-ALX/ FPR2 axis could be exploited to curtail remote damage and enable neuroprotective effects after acute focal brain damage.

Resolvin D1 Halts Remote Neuroinflammation and Improves Functional Recovery after Focal Brain Damage Via ALX/FPR2 Receptor-Regulated MicroRNAs / Bisicchia, Elisa; Sasso, Valeria; Catanzaro, Giuseppina; Leuti, Alessandro; Besharat, Zein Mersini; Chiacchiarini, Martina; Molinari, Marco; Ferretti, Elisabetta; Viscomi, Maria Teresa; Chiurchiù, Valerio. - In: MOLECULAR NEUROBIOLOGY. - ISSN 0893-7648. - (2018), pp. 1-12. [10.1007/s12035-018-0889-z]

Resolvin D1 Halts Remote Neuroinflammation and Improves Functional Recovery after Focal Brain Damage Via ALX/FPR2 Receptor-Regulated MicroRNAs

Catanzaro, Giuseppina;Besharat, Zein Mersini;Chiacchiarini, Martina;Ferretti, Elisabetta;
2018

Abstract

Remote damage is a secondary phenomenon that usually occurs after a primary brain damage in regions that are distant, yet functionally connected, and that is critical for determining the outcomes of several CNS pathologies, including traumatic brain and spinal cord injuries. The understanding of remote damage-associated mechanisms has been mostly achieved in several models of focal brain injury such as the hemicerebellectomy (HCb) experimental paradigm, which helped to identify the involvement of many key players, such as inflammation, oxidative stress, apoptosis and autophagy. Currently, few interventions have been shown to successfully limit the progression of secondary damage events and there is still an unmet need for new therapeutic options. Given the emergence of the novel concept of resolution of inflammation, mediated by the newly identified ω3-derived specialized pro-resolving lipid mediators, such as resolvins, we reported a reduced ability of HCb-injured animals to produce resolvin D1 (RvD1) and an increased expression of its target receptor ALX/FPR2 in remote brain regions. The in vivo administration of RvD1 promoted functional recovery and neuroprotection by reducing the activation of Iba-1+ microglia and GFAP+ astrocytes as well as by impairing inflammatory-induced neuronal cell death in remote regions. These effects were counteracted by intracerebroventricular neutralization of ALX/FPR2, whose activation by RvD1 also down-regulated miR-146b and miR-219a-1-dependent inflammatory markers. In conclusion, we propose that innovative therapies based on RvD1-ALX/ FPR2 axis could be exploited to curtail remote damage and enable neuroprotective effects after acute focal brain damage.
2018
Epigenetics; Inflammation resolution; Neuroinflammation; Remote brain damage; Specialized pro-resolving mediators; Cellular and Molecular Neuroscience
01 Pubblicazione su rivista::01a Articolo in rivista
Resolvin D1 Halts Remote Neuroinflammation and Improves Functional Recovery after Focal Brain Damage Via ALX/FPR2 Receptor-Regulated MicroRNAs / Bisicchia, Elisa; Sasso, Valeria; Catanzaro, Giuseppina; Leuti, Alessandro; Besharat, Zein Mersini; Chiacchiarini, Martina; Molinari, Marco; Ferretti, Elisabetta; Viscomi, Maria Teresa; Chiurchiù, Valerio. - In: MOLECULAR NEUROBIOLOGY. - ISSN 0893-7648. - (2018), pp. 1-12. [10.1007/s12035-018-0889-z]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1063174
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