Endocannabinoids modulate human blood-brain barrier permeabilityin 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...
| Main Authors: | , , , , , |
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| Format: | Article |
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Wiley
2015
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| Online Access: | https://eprints.nottingham.ac.uk/38400/ |
| _version_ | 1848795603046236160 |
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| author | Hind, William H. Tufarelli, Cristina Neophytou, Maria Anderson, Susan I. England, Timothy J. O'Sullivan, Saoirse |
| author_facet | Hind, William H. Tufarelli, Cristina Neophytou, Maria Anderson, Susan I. England, Timothy J. O'Sullivan, Saoirse |
| author_sort | Hind, William H. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| 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 CB2 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, CB1 receptors, TRPV1 channels and CGRP receptors were expressed in both cell types, but mRNA for CB2 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. |
| first_indexed | 2025-11-14T19:34:42Z |
| format | Article |
| id | nottingham-38400 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:34:42Z |
| publishDate | 2015 |
| publisher | Wiley |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-384002020-05-04T20:08:26Z https://eprints.nottingham.ac.uk/38400/ Endocannabinoids modulate human blood-brain barrier permeabilityin vitro Hind, William H. Tufarelli, Cristina Neophytou, Maria Anderson, Susan I. England, Timothy J. O'Sullivan, Saoirse 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 CB2 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, CB1 receptors, TRPV1 channels and CGRP receptors were expressed in both cell types, but mRNA for CB2 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. Wiley 2015-06 Article PeerReviewed Hind, William H., Tufarelli, Cristina, Neophytou, Maria, Anderson, Susan I., England, Timothy J. and O'Sullivan, Saoirse (2015) Endocannabinoids modulate human blood-brain barrier permeabilityin vitro. British Journal of Pharmacology, 172 (12). pp. 3015-3027. ISSN 1476-5381 http://onlinelibrary.wiley.com/doi/10.1111/bph.13106/abstract doi:10.1111/bph.13106 doi:10.1111/bph.13106 |
| spellingShingle | Hind, William H. Tufarelli, Cristina Neophytou, Maria Anderson, Susan I. England, Timothy J. O'Sullivan, Saoirse Endocannabinoids modulate human blood-brain barrier permeabilityin vitro |
| title | Endocannabinoids modulate human blood-brain barrier permeabilityin vitro |
| title_full | Endocannabinoids modulate human blood-brain barrier permeabilityin vitro |
| title_fullStr | Endocannabinoids modulate human blood-brain barrier permeabilityin vitro |
| title_full_unstemmed | Endocannabinoids modulate human blood-brain barrier permeabilityin vitro |
| title_short | Endocannabinoids modulate human blood-brain barrier permeabilityin vitro |
| title_sort | endocannabinoids modulate human blood-brain barrier permeabilityin vitro |
| url | https://eprints.nottingham.ac.uk/38400/ https://eprints.nottingham.ac.uk/38400/ https://eprints.nottingham.ac.uk/38400/ |