Endocannabinoids modulate human blood-brain barrier permeability in vitro

Area of Science:

• Neuroscience
• Physiology
• Pharmacology

Background:

• Endocannabinoids influence epithelial barrier function.
• Stroke elevates cannabinoid receptors and endocannabinoid levels, suggesting neuroprotective roles.
• The role of endocannabinoids in blood-brain barrier (BBB) permeability during normal and ischemic conditions requires elucidation.

Purpose of the Study:

• To investigate the role of endocannabinoids in modulating BBB permeability.
• To explore the mechanisms underlying endocannabinoid action on BBB integrity.
• To assess the potential neuroprotective effects of endocannabinoids in an in vitro model of ischemic stroke.

Main Methods:

• Utilized human brain microvascular endothelial cell and astrocyte co-cultures to model the BBB.
• Simulated ischemia using oxygen-glucose deprivation (OGD) and measured permeability via transepithelial electrical resistance.
• Assessed endocannabinoid effects on baseline and OGD-induced hyperpermeability, investigating target sites with receptor antagonists and real-time PCR.

Main Results:

• Anandamide and oleoylethanolamide (OEA) decreased BBB permeability, mediated by CB2 receptors, TRPV1, CGRP receptor (anandamide), and PPARα (OEA).
• OEA, palmitoylethanolamide, and virodhamine reduced OGD-induced hyperpermeability during reperfusion.
• CB2 receptor mRNA was found in astrocytes, while CB1, TRPV1, and CGRP receptors were expressed in both cell types.

Conclusions:

• Endocannabinoids play a significant role in maintaining normal BBB physiology.
• Endocannabinoids offer protection to the BBB during ischemic stroke through various target sites.
• Findings highlight potential therapeutic avenues for stroke by targeting endocannabinoid pathways.