Response of the cerebral vasculature to systemic carbon monoxide administration—Regional differences and sexual dimorphism
- 13 March 2020
- journal article
- research article
- Published by Wiley in European Journal of Neuroscience
- Vol. 52 (1), 2771-2780
- https://doi.org/10.1111/ejn.14725
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.Keywords
Funding Information
- Fundação para a Ciência e a Tecnologia (SFRH/BD/51969/2012, Pest‐C/SAU/LA0001/2013‐2014, FCT‐UID/NEU/04539/2013—COMPETE, POCI‐01‐0145‐FEDER‐007440, PAC—MEDPERSYST, POCI‐01‐0145‐FEDER‐016428, PTDC/SAU‐NMC/120144/2010, PTDC/NEU‐NMC/0198/2012, FCT‐ANR/NEU‐NMC/0022/2012)
- Federación Española de Enfermedades Raras (CENTRO‐07‐ST24‐FEDER‐002002, CENTRO‐07‐ST24‐FEDER‐002006, CENTRO‐07‐ST24‐FEDER‐002008, CENTRO‐01‐0145‐FEDER‐000016)
This publication has 61 references indexed in Scilit:
- Practical Dynamic Contrast Enhanced MRI in Small Animal Models of Cancer: Data Acquisition, Data Analysis, and InterpretationPharmaceutics, 2012
- Arachidonic acid- and prostaglandin E2-induced cerebral vasodilation is mediated by carbon monoxide, independent of reactive oxygen species in pigletsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2011
- Carbon monoxide as an endogenous vascular modulatorAmerican Journal of Physiology-Heart and Circulatory Physiology, 2011
- Local oestrogenic/androgenic balance in the cerebral vasculatureActa Physiologica, 2011
- Glutathionylation of Adenine Nucleotide Translocase Induced by Carbon Monoxide Prevents Mitochondrial Membrane Permeabilization and ApoptosisOnline Journal of Public Health Informatics, 2010
- Why Sex Matters: Brain Size Independent Differences in Gray Matter Distributions between Men and WomenJournal of Neuroscience, 2009
- Roles of Glia Limitans Astrocytes and Carbon Monoxide in Adenosine Diphosphate-Induced Pial Arteriolar Dilation in Newborn PigsStroke, 2009
- Sex of the cell dictates its response: differential gene expression and sensitivity to cell death inducing stress in male and female cellsThe FASEB Journal, 2009
- Regulation of cerebral vasculature in normal and ischemic brainNeuropharmacology, 2008
- Contributions of astrocytes and CO to pial arteriolar dilation to glutamate in newborn pigsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2006