INTRANASAL DELIVERY OF DEXAMETHASONE EFFICIENTLY CONTROLS LPS-INDUCED MURINE NEUROINFLAMMATION

2017 
Summary Neuroinflammation is the hallmark of several infectious and neurodegenerative diseases. Synthetic glucocorticoids (GCs) are the first-line immunosuppressive drugs used for controlling neuroinflammation. A delayed diffusion of GCs molecules and the high systemic doses required for brain-specific targeting lead to severe undesirable effects, particularly when lifelong treatment is required. Therefore, there is an urgent need for improving this current therapeutic approach. The intranasal (IN) route is being increasingly employed for drug delivery to the brain via the olfactory system. In this study, the IN via is compared to the intravenous (IV) administration of GCs with respect to their effectiveness in controlling neuroinflammation experimentally induced by systemic lipopolysaccharide (LPS) injection. A statistically significant reduction in IL-6 levels in the central nervous system (CNS), in the percentage of CD45+/CD11b+/Ly6G+ and in glial fibrillary acidic protein (GFAP) immunostaining was observed in mice from the IN-dexamethasone (DX) group compared to control and IV-DX-treated animals. DX treatment did not modify the percentage of microglia and perivascular macrophages as determined by Iba1 immunostaining of the cortex and hippocampus. The increased accumulation of DX in brain microvasculature in DX-IN treated mice compared with controls and DX-IV treated animals may underlie the higher effectiveness in controlling neuroinflammation. Altogether, these results indicate that IN-DX administration may offer a more efficient alternative than systemic administration to control neuroinflammation in different neuropathologies. This article is protected by copyright. All rights reserved.
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