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

Abstract

Inflammation 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.

• Authors: M Mecha, A Feliú, P M Iñigo, L Mestre, F J Carrillo-Salinas, C Guaza
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 59 Pg. 141-50 (Nov 2013) ISSN: 1095-953X [Electronic] United States
• PMID: 23851307 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Chemokine CCL2
• Chemokine CCL5
• Interleukin-1beta
• Receptor, Adenosine A2A
• Triazines
• Triazoles
• Vascular Cell Adhesion Molecule-1
• ZM 241385
• Cannabidiol

Topics

• Animals
• Brain (cytology)
• Cannabidiol (therapeutic use)
• Cardiovirus Infections (complications)
• Cell Adhesion (drug effects, physiology)
• Cells, Cultured
• Chemokine CCL2 (genetics, metabolism)
• Chemokine CCL5 (genetics, metabolism)
• Disease Models, Animal
• Endothelial Cells (drug effects, virology)
• Inflammation (drug therapy, etiology)
• Interleukin-1beta (genetics, metabolism)
• Mice
• Motor Activity (drug effects, physiology)
• Multiple Sclerosis (complications, etiology, virology)
• Receptor, Adenosine A2A (genetics, metabolism)
• Triazines (pharmacology)
• Triazoles (pharmacology)
• Vascular Cell Adhesion Molecule-1 (genetics, metabolism)