Response of the cerebral vasculature to systemic carbon monoxide administration - regional differences and sexual dimorphism.

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ID: 100504
2020
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Abstract
Previous studies about the modulation of the vasculature by CO were performed exclusively in male or sexually-immature animals. Understanding the sex differences regarding systemic drug processing and pharmacodynamics is an important feature for safety assessment of drug dosing and efficacy. In this work, we used CORM-A1 as source of CO to examine the effects of this gasotransmitter on brain perfusion and the sex-dependent differences. Dynamic contrast-enhanced imaging (DCE) based analysis was used to characterize the properties of CO in the modulation of cerebral vasculature in vivo, in adult C57BL/6 healthy mice. Perfusion of the temporal muscle, maxillary vein and in hippocampus, cortex and striatum were analyzed for 108 min following CORM-A1 administration of 3 or 5 mg/kg. Under control conditions brain perfusion was lower in females when compared with males. Under CO treatment, females showed a surprisingly overall reduced perfusion compared to controls (F=3.452, p=0.0004), while no major alterations (or even the expected increase) were observed in males. Cortical structures were only modulated in females. A striking female-dominated vasoconstriction effect was observed in the hippocampus and striatum following administration of CO, in this mixed-sex cohort. Since these two regions are implicated in episodic and procedural memory formation, CO may have a relevant impact in learning and memory.
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oliveira2020responsethe Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Sara R Oliveira, João Castelhano, José Sereno, Helena L A Vieira, Carlos B Duarte, Miguel Castelo-Branco
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Journal the european journal of neuroscience
Year 2020
DOI
10.1111/ejn.14725
URL
Keywords
MRI sex differences dynamic contrast-enhanced imaging (dce) vasomodulation

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