Intranasal Dexamethasone Reduces Mortality and Brain Damage in a Mouse Experimental Ischemic Stroke Model View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-07-06

AUTHORS

Alejandro Espinosa, Gabriela Meneses, Anahí Chavarría, Raúl Mancilla, José Pedraza-Chaverri, Agnes Fleury, Brandon Bárcena, Ivan N. Pérez-Osorio, Hugo Besedovsky, Antonio Arauz, Gladis Fragoso, Edda Sciutto

ABSTRACT

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. More... »

PAGES

1907-1918

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s13311-020-00884-9

DOI

http://dx.doi.org/10.1007/s13311-020-00884-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1129028047

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32632775


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