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Cannabidiol protects an in vitro model of the blood brain barrier (BBB) from oxygen-glucose deprivation via PPARγ and 5-HT1A

Hind, William H.; England, Timothy J.; O'Sullivan, Saoirse E.

Authors

William H. Hind

Saoirse E. O'Sullivan



Abstract

Background and Purpose: In vivo and in vitro studies have demonstrated a protective effect of cannabidiol (CBD) in reducing infarct size in stroke models and against epithelial barrier damage in numerous disease models. We aimed to investigate whether CBD also affects blood–brain barrier (BBB) permeability following ischaemia.
Experimental Approach: Human brain microvascular endothelial cell (HBMEC) and human astrocyte co‐cultures modelled the BBB. Ischaemia was modelled by oxygen–glucose deprivation (OGD) and permeability was measured by transepithelial electrical resistance.
Key Results: CBD (10 μM) prevented the increase in permeability caused by 4 h OGD. CBD was most effective when administered before the OGD, but protective effects were observed up to 2 h into reperfusion. This protective effect was inhibited by a PPARγ antagonist and partly reduced by a 5‐HT1A receptor antagonist, but was unaffected by antagonists of cannabinoid CB1 or CB2 receptors, TRPV1 channels or adenosine A2A receptors. CBD also reduced cell damage, as measured by LDH release and by markers of cellular adhesion, such as the adhesion molecule VCAM‐1. In HBMEC monocultures, CBD decreased VCAM‐1 and increased VEGF levels, effects which were inhibited by PPARγ antagonism.
Conclusions and Implications: These data suggest that preventing permeability changes at the BBB could represent an as yet unrecognized mechanism of CBD‐induced neuroprotection in ischaemic stroke, a mechanism mediated by activation of PPARγ and 5‐HT1A receptors.

Citation

Hind, W. H., England, T. J., & O'Sullivan, S. E. (2016). Cannabidiol protects an in vitro model of the blood brain barrier (BBB) from oxygen-glucose deprivation via PPARγ and 5-HT1A. British Journal of Pharmacology, 173(5), 815-825. doi:10.1111/bph.13368

Journal Article Type Article
Acceptance Date Oct 13, 2015
Online Publication Date Oct 24, 2015
Publication Date Mar 1, 2016
Deposit Date Sep 13, 2018
Publicly Available Date
Print ISSN 0007-1188
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 173
Issue 5
Pages 815-825
DOI https://doi.org/10.1111/bph.13368
Public URL https://nottingham-repository.worktribe.com/output/1106192
Publisher URL https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.13368