title: Early modulation of pro-inflammatory microglia by minocycline loaded nanoparticles confers long lasting protection after spinal cord injury.
abstract: Many efforts have been performed in order to understand the role of recruited macrophages in the progression of spinal cord injury (SCI). Different studies revealed a pleiotropic effect played by these cells associated to distinct phenotypes (M1 and M2), showing a predictable spatial and temporal distribution in the injured site after SCI. Differently, the role of activated microglia in injury progression has been poorly investigated, mainly because of the challenges to target and selectively modulate them in situ. A delivery nanovector tool (poly-ε-caprolactone-based nanoparticles) able to selectively treat/target microglia has been developed and used here to clarify the temporal and spatial involvement of the pro-inflammatory response associated to microglial cells in SCI. We show that a treatment with nanoparticles loaded with minocycline, the latter a well-known anti-inflammatory drug, when administered acutely in a SCI mouse model is able to efficiently modulate the resident microglial cells reducing the pro-inflammatory response, maintaining a pro-regenerative milieu and ameliorating the behavioral outcome up to 63 days post injury. Furthermore, by using this selective delivery tool we demonstrate a mechanistic link between early microglia activation and M1 macrophages recruitment to the injured site via CCL2 chemokine, revealing a detrimental contribution of pro-inflammatory macrophages to injury progression after SCI.
authors.affiliation: Dipartimento di Neuroscienze, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milan, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Papa
authors.affiliation: Dipartimento di Neuroscienze, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Caron
authors.affiliation: Dipartimento di Oncologia, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milan, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Erba
authors.affiliation: Dipartimento di Oncologia, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milan, Italy.
authors.forename: Nicolò
authors.initials: N
authors.lastname: Panini
authors.affiliation: Dipartimento di Ambiente e Salute, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milan, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: De Paola
authors.affiliation: Dipartimento di Ambiente e Salute, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mariani
authors.affiliation: Institute for Chemical and Bioengineering, ETH Zurich, Vladimir Perlog Weg 1, 8093 Zurich, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Colombo
authors.affiliation: Dipartimento di Chimica, Materiali e Ingegneria Chimica "Giulio Natta", Politecnico di Milano, via Mancinelli 7, 20131 Milan, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferrari
authors.affiliation: Dipartimento di Neuroscienze, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milan, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Pozzer
authors.affiliation: Dipartimento di Neuroscienze, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milan, Italy.
authors.forename: Elisa R
authors.initials: ER
authors.lastname: Zanier
authors.affiliation: Dipartimento di Neuroscienze, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pischiutta
authors.affiliation: Dipartimento di Biochimica e Farmacologia Molecolare, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milan, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Lucchetti
authors.affiliation: Dipartimento di Fisica, Politecnico di Milano, P.zza Leonardo da Vinci 32, 20133 Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bassi
authors.affiliation: Dipartimento di Fisica, Politecnico di Milano, P.zza Leonardo da Vinci 32, 20133 Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Valentini
authors.affiliation: Dipartimento di Fisica, Politecnico di Milano, P.zza Leonardo da Vinci 32, 20133 Milan, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Simonutti
authors.affiliation: Dipartimento di Chimica, Materiali e Ingegneria Chimica "Giulio Natta", Politecnico di Milano, via Mancinelli 7, 20131 Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Rossi
authors.affiliation: Dipartimento di Chimica, Materiali e Ingegneria Chimica "Giulio Natta", Politecnico di Milano, via Mancinelli 7, 20131 Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Moscatelli
authors.affiliation: Dipartimento di Neuroscienze, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milan, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.affiliation: Dipartimento di Neuroscienze, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milan, Italy. Electronic address: pietro.veglianese@marionegri.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Veglianese
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D007249:Inflammation / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology*; D008911:Minocycline / Q000627:therapeutic use*; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry*; D009416:Nerve Regeneration / Q000187:drug effects; D010641:Phenotype; D011091:Polyesters / Q000737:chemistry; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D018932:Chemokine CCL2; D011091:Polyesters; C016240:polycaprolactone; D008911:Minocycline
keywords: Inflammation; Macrophages; Microglia; Minocycline; Nanoaprticles; Spinal cord injury