Intranasal Dexamethasone Reduces Mortality and Brain Damage in a Mouse Experimental Ischemic Stroke Model
Por:
Espinosa A., Meneses G., Chavarría A., Mancilla R., Pedraza-Chaverri J., Fleury A., Bárcena B., Pérez-Osorio I.N., Besedovsky H., Arauz A., Fragoso G., Sciutto E.
Publicada:
1 oct 2020
Ahead of Print:
1 ene 2020
Resumen:
Neuroinflammation triggered by the expression of damaged-associated molecular patterns released from dying cells plays a critical role in the pathogenesis of ischemic stroke. However, the benefits from the control of neuroinflammation in the clinical outcome have not been established. In this study, the effectiveness of intranasal, a highly efficient route to reach the central nervous system, and intraperitoneal dexamethasone administration in the treatment of neuroinflammation was evaluated in a 60-min middle cerebral artery occlusion (MCAO) model in C57BL/6 male mice. We performed a side-by-side comparison using intranasal versus intraperitoneal dexamethasone, a timecourse including immediate (0 h) or 4 or 12 h poststroke intranasal administration, as well as 4 intranasal doses of dexamethasone beginning 12 h after the MCAO versus a single dose at 12 h to identify the most effective conditions to treat neuroinflammation in MCAO mice. The best results were obtained 12 h after MCAO and when mice received a single dose of dexamethasone (0.25 mg/kg) intranasally. This treatment significantly reduced mortality, neurological deficits, infarct volume size, blood–brain barrier permeability in the somatosensory cortex, inflammatory cell infiltration, and glial activation. Our results demonstrate that a single low dose of intranasal dexamethasone has neuroprotective therapeutic effects in the MCAO model, showing a better clinical outcome than the intraperitoneal administration. Based on these results, we propose a new therapeutic approach for the treatment of the damage process that accompanies ischemic stroke. © 2020, The American Society for Experimental NeuroTherapeutics, Inc.
Filiaciones:
Espinosa A.:
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Meneses G.:
Departamento de Parasitología, Instituto Nacional de Diagnóstico y Referencia Epidemiológicos, Mexico City, 01480, Mexico
Chavarría A.:
Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, 06726, Mexico
Mancilla R.:
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Pedraza-Chaverri J.:
Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Fleury A.:
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Unidad Periférica del Instituto de Investigaciones Biomédicas en el Instituto Nacional de Neurología y Neurocirugía, Mexico City, 14269, Mexico
Bárcena B.:
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Pérez-Osorio I.N.:
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Besedovsky H.:
The Institute of Physiology and Pathophysiology, Medical Faculty, Philipps University, Marburg, D-35037, Germany
Arauz A.:
Stroke Clinic, Instituto Nacional de Neurología y Neurocirugía, Mexico City, 14269, Mexico
Fragoso G.:
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Sciutto E.:
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
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