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Adenosine receptor agonist NECA increases cerebral extravasation of fluorescein and low molecular weight dextran independent of blood-brain barrier modulation

Conventional methods for therapeutic blood-brain barrier (BBB) disruption facilitate drug delivery but are cumbersome to perform. A previous study demonstrated that adenosine receptor (AR) stimulation by 5′-N-ethylcarboxamide adenosine (NECA) increased the extravasation of intravascular tracers into...

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Autores principales: Cheng, Chih-Chung, Yang, Ya Lan, Liao, Kate Hsiurong, Lai, Ted Weita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812297/
https://www.ncbi.nlm.nih.gov/pubmed/27025761
http://dx.doi.org/10.1038/srep23882
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author Cheng, Chih-Chung
Yang, Ya Lan
Liao, Kate Hsiurong
Lai, Ted Weita
author_facet Cheng, Chih-Chung
Yang, Ya Lan
Liao, Kate Hsiurong
Lai, Ted Weita
author_sort Cheng, Chih-Chung
collection PubMed
description Conventional methods for therapeutic blood-brain barrier (BBB) disruption facilitate drug delivery but are cumbersome to perform. A previous study demonstrated that adenosine receptor (AR) stimulation by 5′-N-ethylcarboxamide adenosine (NECA) increased the extravasation of intravascular tracers into the brain and proposed that AR agonism may be an effective method for therapeutic BBB disruption. We attempted to confirm the extravasation of tracers into the brain and also investigated tracer extravasation into peripheral organs and tracer retention in the blood. We found that NECA not only increased the extravasation of intravascular fluorescein and low molecular weight dextran into the brain of mice but also increased the concentrations of these tracers in the blood. In fact, the brain:blood ratio-normalized BBB permeability for either tracer is actually decreased by NECA administration. Elevated blood urea nitrogen levels in mice following NECA treatment suggested that renal function impairment was a probable cause of tracer retention. Therefore, NECA has almost no effect on the extravasation of intravascular Evans blue dye (EBD), an albumin-binding tracer with little renal clearance. Rather than inducing BBB disruption, our study demonstrated that NECA increased tracer extravasation into the brain by increasing the concentration gradient of the tracer across the BBB.
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spelling pubmed-48122972016-04-04 Adenosine receptor agonist NECA increases cerebral extravasation of fluorescein and low molecular weight dextran independent of blood-brain barrier modulation Cheng, Chih-Chung Yang, Ya Lan Liao, Kate Hsiurong Lai, Ted Weita Sci Rep Article Conventional methods for therapeutic blood-brain barrier (BBB) disruption facilitate drug delivery but are cumbersome to perform. A previous study demonstrated that adenosine receptor (AR) stimulation by 5′-N-ethylcarboxamide adenosine (NECA) increased the extravasation of intravascular tracers into the brain and proposed that AR agonism may be an effective method for therapeutic BBB disruption. We attempted to confirm the extravasation of tracers into the brain and also investigated tracer extravasation into peripheral organs and tracer retention in the blood. We found that NECA not only increased the extravasation of intravascular fluorescein and low molecular weight dextran into the brain of mice but also increased the concentrations of these tracers in the blood. In fact, the brain:blood ratio-normalized BBB permeability for either tracer is actually decreased by NECA administration. Elevated blood urea nitrogen levels in mice following NECA treatment suggested that renal function impairment was a probable cause of tracer retention. Therefore, NECA has almost no effect on the extravasation of intravascular Evans blue dye (EBD), an albumin-binding tracer with little renal clearance. Rather than inducing BBB disruption, our study demonstrated that NECA increased tracer extravasation into the brain by increasing the concentration gradient of the tracer across the BBB. Nature Publishing Group 2016-03-30 /pmc/articles/PMC4812297/ /pubmed/27025761 http://dx.doi.org/10.1038/srep23882 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Cheng, Chih-Chung
Yang, Ya Lan
Liao, Kate Hsiurong
Lai, Ted Weita
Adenosine receptor agonist NECA increases cerebral extravasation of fluorescein and low molecular weight dextran independent of blood-brain barrier modulation
title Adenosine receptor agonist NECA increases cerebral extravasation of fluorescein and low molecular weight dextran independent of blood-brain barrier modulation
title_full Adenosine receptor agonist NECA increases cerebral extravasation of fluorescein and low molecular weight dextran independent of blood-brain barrier modulation
title_fullStr Adenosine receptor agonist NECA increases cerebral extravasation of fluorescein and low molecular weight dextran independent of blood-brain barrier modulation
title_full_unstemmed Adenosine receptor agonist NECA increases cerebral extravasation of fluorescein and low molecular weight dextran independent of blood-brain barrier modulation
title_short Adenosine receptor agonist NECA increases cerebral extravasation of fluorescein and low molecular weight dextran independent of blood-brain barrier modulation
title_sort adenosine receptor agonist neca increases cerebral extravasation of fluorescein and low molecular weight dextran independent of blood-brain barrier modulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812297/
https://www.ncbi.nlm.nih.gov/pubmed/27025761
http://dx.doi.org/10.1038/srep23882
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