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Endocannabinoids modulate human blood–brain barrier permeability in vitro
BACKGROUND AND PURPOSE: Endocannabinoids alter permeability at various epithelial barriers, and cannabinoid receptors and endocannabinoid levels are elevated by stroke, with potential neuroprotective effects. We therefore explored the role of endocannabinoids in modulating blood–brain barrier (BBB)...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459020/ https://www.ncbi.nlm.nih.gov/pubmed/25651941 http://dx.doi.org/10.1111/bph.13106 |
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author | Hind, William H Tufarelli, Cristina Neophytou, Maria Anderson, Susan I England, Timothy J O'Sullivan, Saoirse E |
author_facet | Hind, William H Tufarelli, Cristina Neophytou, Maria Anderson, Susan I England, Timothy J O'Sullivan, Saoirse E |
author_sort | Hind, William H |
collection | PubMed |
description | BACKGROUND AND PURPOSE: Endocannabinoids alter permeability at various epithelial barriers, and cannabinoid receptors and endocannabinoid levels are elevated by stroke, with potential neuroprotective effects. We therefore explored the role of endocannabinoids in modulating blood–brain barrier (BBB) permeability in normal conditions and in an ischaemia/reperfusion model. EXPERIMENTAL APPROACH: Human brain microvascular endothelial cell and astrocyte co-cultures modelled the BBB. Ischaemia was modelled by oxygen-glucose deprivation (OGD) and permeability was measured by transepithelial electrical resistance. Endocannabinoids or endocannabinoid-like compounds were assessed for their ability to modulate baseline permeability or OGD-induced hyperpermeability. Target sites of action were investigated using receptor antagonists and subsequently identified with real-time PCR. KEY RESULTS: Anandamide (10 μM) and oleoylethanolamide (OEA, 10 μM) decreased BBB permeability (i.e. increased resistance). This was mediated by cannabinoid CB(2) receptors, transient receptor potential vanilloid 1 (TRPV1) channels, calcitonin gene-regulated peptide (CGRP) receptor (anandamide only) and PPARα (OEA only). Application of OEA, palmitoylethanolamide (both PPARα mediated) or virodhamine (all 10 μM) decreased the OGD-induced increase in permeability during reperfusion. 2-Arachidonoyl glycerol, noladin ether and oleamide did not affect BBB permeability in normal or OGD conditions. N-arachidonoyl-dopamine increased permeability through a cytotoxic mechanism. PPARα and γ, CB(1) receptors, TRPV1 channels and CGRP receptors were expressed in both cell types, but mRNA for CB(2) receptors was only present in astrocytes. CONCLUSION AND IMPLICATION: The endocannabinoids may play an important modulatory role in normal BBB physiology, and also afford protection to the BBB during ischaemic stroke, through a number of target sites. |
format | Online Article Text |
id | pubmed-4459020 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-44590202015-11-02 Endocannabinoids modulate human blood–brain barrier permeability in vitro Hind, William H Tufarelli, Cristina Neophytou, Maria Anderson, Susan I England, Timothy J O'Sullivan, Saoirse E Br J Pharmacol Research Papers BACKGROUND AND PURPOSE: Endocannabinoids alter permeability at various epithelial barriers, and cannabinoid receptors and endocannabinoid levels are elevated by stroke, with potential neuroprotective effects. We therefore explored the role of endocannabinoids in modulating blood–brain barrier (BBB) permeability in normal conditions and in an ischaemia/reperfusion model. EXPERIMENTAL APPROACH: Human brain microvascular endothelial cell and astrocyte co-cultures modelled the BBB. Ischaemia was modelled by oxygen-glucose deprivation (OGD) and permeability was measured by transepithelial electrical resistance. Endocannabinoids or endocannabinoid-like compounds were assessed for their ability to modulate baseline permeability or OGD-induced hyperpermeability. Target sites of action were investigated using receptor antagonists and subsequently identified with real-time PCR. KEY RESULTS: Anandamide (10 μM) and oleoylethanolamide (OEA, 10 μM) decreased BBB permeability (i.e. increased resistance). This was mediated by cannabinoid CB(2) receptors, transient receptor potential vanilloid 1 (TRPV1) channels, calcitonin gene-regulated peptide (CGRP) receptor (anandamide only) and PPARα (OEA only). Application of OEA, palmitoylethanolamide (both PPARα mediated) or virodhamine (all 10 μM) decreased the OGD-induced increase in permeability during reperfusion. 2-Arachidonoyl glycerol, noladin ether and oleamide did not affect BBB permeability in normal or OGD conditions. N-arachidonoyl-dopamine increased permeability through a cytotoxic mechanism. PPARα and γ, CB(1) receptors, TRPV1 channels and CGRP receptors were expressed in both cell types, but mRNA for CB(2) receptors was only present in astrocytes. CONCLUSION AND IMPLICATION: The endocannabinoids may play an important modulatory role in normal BBB physiology, and also afford protection to the BBB during ischaemic stroke, through a number of target sites. BlackWell Publishing Ltd 2015-06 2015-04-10 /pmc/articles/PMC4459020/ /pubmed/25651941 http://dx.doi.org/10.1111/bph.13106 Text en © 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Research Papers Hind, William H Tufarelli, Cristina Neophytou, Maria Anderson, Susan I England, Timothy J O'Sullivan, Saoirse E Endocannabinoids modulate human blood–brain barrier permeability in vitro |
title | Endocannabinoids modulate human blood–brain barrier permeability in vitro |
title_full | Endocannabinoids modulate human blood–brain barrier permeability in vitro |
title_fullStr | Endocannabinoids modulate human blood–brain barrier permeability in vitro |
title_full_unstemmed | Endocannabinoids modulate human blood–brain barrier permeability in vitro |
title_short | Endocannabinoids modulate human blood–brain barrier permeability in vitro |
title_sort | endocannabinoids modulate human blood–brain barrier permeability in vitro |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459020/ https://www.ncbi.nlm.nih.gov/pubmed/25651941 http://dx.doi.org/10.1111/bph.13106 |
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