Mecha M, Feliú A, Iñigo PM, Mestre L, Carrillo-Salinas FJ, Guaza C.
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