title: Functions of the CB1 and CB 2 receptors in neuroprotection at the level of the blood-brain barrier.
abstract: The cannabinoid (CB) receptors are the main targets of the cannabinoids, which include plant cannabinoids, endocannabinoids and synthetic cannabinoids. Over the last few years, accumulated evidence has suggested a role of the CB receptors in neuroprotection. The blood-brain barrier (BBB) is an important brain structure that is essential for neuroprotection. A link between the CB receptors and the BBB is thus likely, but this possible connection has only recently gained attention. Cannabinoids and the BBB share the same mechanisms of neuroprotection and both protect against excitotoxicity (CB1), cell death (CB1), inflammation (CB2) and oxidative stress (possibly CB independent)-all processes that also damage the BBB. Several examples of CB-mediated protection of the BBB have been found, such as inhibition of leukocyte influx and induction of amyloid beta efflux across the BBB. Moreover, the CB receptors were shown to improve BBB integrity, particularly by restoring the tightness of the tight junctions. This review demonstrated that both CB receptors are able to restore the BBB and neuroprotection, but much uncertainty about the underlying signaling cascades still exists and further investigation is needed.
authors.affiliation: Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333CC, PO Box 9502, 2300 RA, Leiden, The Netherlands.
authors.forename: Esmée
authors.initials: E
authors.lastname: Vendel
authors.forename: Elizabeth C M
authors.initials: EC
authors.lastname: de Lange
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002186:Cannabinoids / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D004660:Encephalitis / Q000503:physiopathology / Q000517:prevention & control; D063388:Endocannabinoids / Q000819:agonists / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D043885:Receptor, Cannabinoid, CB2 / Q000502:physiology*; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002186:Cannabinoids; D063388:Endocannabinoids; D018696:Neuroprotective Agents; D009498:Neurotoxins; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2