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Cannabidiol protects an in vitro model of the blood–brain barrier from oxygen‐glucose deprivation via PPARγ and 5‐HT 1A receptors
Author(s) -
Hind William H,
England Timothy J,
O'Sullivan Saoirse E
Publication year - 2016
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13368
Subject(s) - cannabidiol , blood–brain barrier , pharmacology , neuroprotection , receptor , cannabinoid , chemistry , receptor antagonist , antagonist , biology , medicine , biochemistry , endocrinology , central nervous system , cannabis , psychiatry
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‐HT 1A receptor antagonist, but was unaffected by antagonists of cannabinoid CB 1 or CB 2 receptors, TRPV1 channels or adenosine A 2A 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‐HT 1A receptors.