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Biocompatible highly bright silica nanoparticles were designed, prepared and tested in small living organisms for both in vivo and ex vivo imaging. The results that we report here demonstrate that they are suitable for optical imaging applications as a possible alternative to commercially available fluorescent materials including quantum dots. Moreover, the tunability of their photophysical properties, which was enhanced by the use of different dyes as doping agents, constitutes a very important added value in the field of medical diagnostics.

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BACKGROUND AND PURPOSENeuroinflammation is initiated by a variety of stimuli including infections, sepsis, neurodegenerative diseases or traumatic brain injury and, if not adequately controlled, can lead to various degrees of neuronal damage and behavioural impairment. A critical event in the initial steps of inflammation is neutrophil extravasation. Semicarbazide-sensitive amine oxidase (SSAO, also known as vascular adhesion protein 1 or VAP-1) regulates neutrophil adhesion and extravasation. Here, we elucidate the role of SSAO/VAP-1 in the early stage inflammatory response after LPS insult in the brain. EXPERIMENTAL APPROACHPXS-4681A, a selective and irreversible SSAO/VAP-1 inhibitor, was tested in two rat models of neuroinflammation, following systemic or i.c.v. LPS. Immunohistochemical and immunofluorescence techniques were used to measure neutrophils and microglia. VAP-1 was quantitated by Western blotting. KEY RESULTSBoth systemic and i.c.v. administration of LPS induced an increase in neutrophil recruitment and microglial response in various brain areas including the substantia nigra and striatum. PXS-4681A produced a significant inhibition of neutrophil recruitment and extravasation after i.c.v. LPS injection and also reversed microglial cell recruitment and morphological changes to the level of the sham controls in both LPS models. CONCLUSIONS AND IMPLICATIONSPXS-4681A acted as an effective anti-inflammatory agent after both systemic and i.c.v. LPS injections suggesting that SSAO/VAP-1 inhibition could be beneficial in the treatment of brain inflammation. AbbreviationsBBB, blood-brain barrier; BCA, bicinchoninic acid; DAB, 3,3 0 -diaminobenzidine; Iba-1, ionized calcium-binding adapter molecule 1; MPO, myeloperoxidase; PFA, paraformaldehyde; RECA-1, rat endothelial cell antibody 1; SSAO, semicarbazidesensitive amine oxidase; VAP-1, vascular adhesion protein 1