Intranasal delivery of dexamethasone efficiently controls LPS-induced murine neuroinflammation
Por:
Meneses, G., Gevorkian, G., Florentino, A., Bautista, M. A., Espinosa, A., Acero, G., Diaz, G., Fleury, A., Perez Osorio, I. N., del Rey, A., Fragoso, G., Sciutto, E., Besedovsky, H.
Publicada:
1 dic 2017
Resumen:
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 (i.n.) route is being employed increasingly for drug delivery to the brain via the olfactory system. In this study, the i.n. route is compared to the intravenous (i.v.) administration of GCs with respect to their effectiveness in controlling neuroinflammation induced experimentally by systemic lipopolysaccharide (LPS) injection. A statistically significant reduction in interleukin (IL)-6 levels in the central nervous system (CNS) in the percentage of CD45+/CD11b+/lymphocyte antigen 6 complex locus G6D [Ly6G+ and in glial fibrillary acidic protein (GFAP) immunostaining was observed in mice from the i.n.-dexamethasone (DX] group compared to control and i.v.-DX-treated animals. DX treatment did not modify the percentage of microglia and perivascular macrophages as determined by ionized calcium binding adaptor molecule 1 (Iba1) immunostaining of the cortex and hippocampus. The increased accumulation of DX in brain microvasculature in DX-i.n.-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. © 2017 British Society for Immunology
Filiaciones:
Meneses, G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228, Mexico City 04510, DF, Mexico
Gevorkian, G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228, Mexico City 04510, DF, Mexico
Florentino, A.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228, Mexico City 04510, DF, Mexico
Bautista, M. A.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228, Mexico City 04510, DF, Mexico
Espinosa, A.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228, Mexico City 04510, DF, Mexico
Acero, G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228, Mexico City 04510, DF, Mexico
Diaz, G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228, Mexico City 04510, DF, Mexico
Fleury, A.:
Inst Nacl Neurol & Neurocirug, Inst Invest Biomed, Unidad Perifer, Mexico City, DF, Mexico
Perez Osorio, I. N.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228, Mexico City 04510, DF, Mexico
del Rey, A.:
Philipps Univ, Fac Med, Inst Physiol & Pathophysiol, Marburg, Germany
Fragoso, G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228, Mexico City 04510, DF, Mexico
Sciutto, E.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228, Mexico City 04510, DF, Mexico
Besedovsky, H.:
Philipps Univ, Fac Med, Inst Physiol & Pathophysiol, Marburg, Germany
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