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

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 intranasalversus 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 MCAOversus 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 volu me 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.

Source: Neurotherapeutics - July 5, 2020 Category: Neurology Source Type: research