Stroke, Volume 54, Issue Suppl_1, Page AWP227-AWP227, February 1, 2023. Cerebrovascular dysfunction leading to brain hypoperfusion is an early event in vascular cognitive impairment & dementia (VCID). Postmortem brain levels of endothelin (ET)-1, the most potent vasoconstrictor, closely correlate with blood barrier breakdown and hypoperfusion in individuals with VCID. The prevalence of diabetes in people with dementia is as high as 39%. We have reported that there is upregulation of circulating and brain ET-1 in diabetic male rats that later develop cognitive impairment and all the cell types of the neurovascular unit express ETA receptors. We hypothesized that inhibition of brain ETA receptors can prevent cognitive decline in diabetes.Methods:Experimental design is depicted in Fig 1. The impact of unilateral common carotid occlusion (UCCAO) on ETA receptor expression and brain hypoxia was assessed by immunohistochemistry. A battery of cognitive tests was performed.Results:Bioavailability of drug in brain post intranasal delivery was confirmed by LCMS. UCCAO increased the expression of HIF1a and ETA receptors in most of the cell types of NVU. Mobility of diabetic animals was significantly reduced (1522±272.8cm control vs 1051±61.17cm diabetic; p
Abstract WP227: Endothelin Receptor A (eta) Inhibition By Intranasal Administration Of Bq-123 In Hypoperfused Diabetic Rats Exerts Different Effects In Various Domains Of Cognition
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Febbraio 2023
