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Title

Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A2A receptors

AuthorsMecha, Miriam ; Feliú, Ana; Iñigo, P.M.; Mestre, Leyre ; Carrillo-Salinas, F. J.; Guaza, Carmen
KeywordsCCL5
very late antigen-4
tetrahydrocannabinol
multiple sclerosis
experimental autoimmune encephalomyelitis
chemokine receptor 2
Adenosine
BBB
CBD
CCL2
CCR2
CNS
Cannabidiol
Chemokines
EAE
Infiltrates
Inflammation
MS
Microglia
Multiple sclerosis
THC
TMEV-IDD
Theiler's murine encephalomyelitis virus
Theiler's murine encephalomyelitis virus-induced demyelinating disease
VCAM-1
VLA-4
blood brain barrier
cannabidiol
central nervous system
chemokine ligand 2
chemokine ligand 5
Issue DateNov-2013
PublisherAcademic Press
CitationNeurobiology of Disease 59: 141-150 (2013)
AbstractInflammation in the central nervous system (CNS) is a complex process that involves a multitude of molecules and effectors, and it requires the transmigration of blood leukocytes across the blood-brain barrier (BBB) and the activation of resident immune cells. Cannabidiol (CBD), a non-psychotropic cannabinoid constituent of Cannabis sativa, has potent anti-inflammatory and immunosuppressive properties. Yet, how this compound modifies the deleterious effects of inflammation in TMEV-induced demyelinating disease (TMEV-IDD) remains unknown. Using this viral model of multiple sclerosis (MS), we demonstrate that CBD decreases the transmigration of blood leukocytes by downregulating the expression of vascular cell adhesion molecule-1 (VCAM-1), chemokines (CCL2 and CCL5) and the proinflammatory cytokine IL-1β, as well as by attenuating the activation of microglia. Moreover, CBD administration at the time of viral infection exerts long-lasting effects, ameliorating motor deficits in the chronic phase of the disease in conjunction with reduced microglial activation and pro-inflammatory cytokine production. Adenosine A2A receptors participate in some of the anti-inflammatory effects of CBD, as the A2A antagonist ZM241385 partially blocks the protective effects of CBD in the initial stages of inflammation. Together, our findings highlight the anti-inflammatory effects of CBD in this viral model of MS and demonstrate the significant therapeutic potential of this compound for the treatment of pathologies with an inflammatory component. © 2013 The Authors.
Publisher version (URL)http://doi.org/10.1016/j.nbd.2013.06.016
URIhttp://hdl.handle.net/10261/150506
DOI10.1016/j.nbd.2013.06.016
Identifiersdoi: 10.1016/j.nbd.2013.06.016
issn: 0969-9961
Appears in Collections:(IC) Artículos
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