Early modulation of pro-inflammatory microglia by minocycline loaded nanoparticles confers long lasting protection after spinal cord injury

Simonetta Papa, Ilaria Caron, Eugenio Erba, Nicolò Panini, Massimiliano De Paola, Alessandro Mariani, Claudio Colombo, Raffaele Ferrari, Diego Pozzer, Elisa R. Zanier, Francesca Pischiutta, Jacopo Lucchetti, Andrea Bassi, Gianluca Valentini, Giulio Simonutti, Filippo Rossi, Davide Moscatelli, Gianluigi Forloni, Pietro Veglianese

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)13-24
Number of pages12
JournalBiomaterials
Volume75
DOIs
Publication statusPublished - Jan 1 2016

Keywords

  • Inflammation
  • Macrophages
  • Microglia
  • Minocycline
  • Nanoaprticles
  • Spinal cord injury

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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