Cannabidiol protects an in vitro model of the blood brain barrier (BBB) from oxygen-glucose deprivation via PPARγ and 5-HT1A.
Br J Pharmacol. 2015 Oct 24. Epub 2015 Oct 24. PMID: 26497782
William H Hind
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 (HA) 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 pre-OGD, but protective effects were observed up to 2 h into reperfusion. This effect was inhibited by a peroxisome proliferator-activated receptor gamma (PPARγ) antagonist, and partiallyreduced by a serotonin (5-HT1A ) antagonist (but was unaffected by antagonists of CB1 , CB2 , TRPV1 or adenosine A2A ). CBD also reduced cell damage (lactate dehydrogenase) and markers of cellular adhesion (VCAM-1). In HBMEC monocultures, CBD decreased vascular cell adhesion protein 1 (VCAM-1) and increased vascular endothelial growth factor (VEGF), which was inhibited by PPARγ antagonism.
CONCLUSIONS AND IMPLICATIONS: These data suggest that activity at the BBB could represent an as yet unrecognised mechanism of CBD-induced neuroprotection in ischaemic stroke, mediated by PPARγ and 5-HT1A . This article is protected by copyright. All rights reserved.